Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM.

Science.gov (United States)

Tamada, Hiromi; Kiryu-Seo, Sumiko; Hosokawa, Hiroki; Ohta, Keisuke; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Nakamura, Kei-Ichiro; Kiyama, Hiroshi

2017-08-01

Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously. Crossing of dynamin-related protein 1 (Drp1) gene-floxed mice with neuronal injury-specific Cre driver mice, Atf3:BAC Tg mice, allowed for Drp1 ablation specifically in injured neurons. FIB/SEM analysis demonstrated that somatic mitochondrial morphologies in motor neurons were not altered before or after nerve injury. However, the fission impairment resulted in prominent somatic mitochondrial enlargement, which initially induced complex morphologies with round regions and long tubular processes, subsequently causing a decrease in the number of processes and further enlargement of the round regions, which eventually resulted in big spheroidal mitochondria without processes. The abnormal mitochondria exhibited several degradative morphologies: local or total cristae collapse, vacuolization, and mitophagy. These suggest that mitochondrial fission is crucial for maintaining mitochondrial integrity in injured motor neurons, and multiple forms of mitochondria degradation may accelerate neuronal degradation. © 2017 Wiley Periodicals, Inc.

Adhesion Regulating Molecule 1 Mediates HAP40 Overexpression-Induced Mitochondrial Defects

Science.gov (United States)

Huang, Zih-Ning; Chung, Her Min; Fang, Su-Chiung; Her, Lu-Shiun

2017-01-01

Striatal neuron death in Huntington's disease is associated with abnormal mitochondrial dynamics and functions. However, the mechanisms for this mitochondrial dysregulation remain elusive. Increased accumulation of Huntingtin-associated protein 40 (HAP40) has been shown to be associated with Huntington's disease. However, the link between increased HAP40 and Huntington's disease remains largely unknown. Here we show that HAP40 overexpression causes mitochondrial dysfunction and reduces cell viability in the immortalized mouse striatal neurons. HAP40-associated mitochondrial dysfunction is associated with reduction of adhesion regulating molecule 1 (ADRM1) protein. Consistently, depletion of ADRM1 by shRNAs impaired mitochondrial functions and increased mitochondrial fragmentation in mouse striatal cells. Moreover, reducing ADRM1 levels enhanced activity of fission factor dynamin-related GTPase protein 1 (Drp1) via increased phosphorylation at serine 616 of Drp1 (Drp1Ser616). Restoring ADRM1 protein levels was able to reduce HAP40-induced ROS levels and mitochondrial fragmentation and improved mitochondrial functions and cell viability. Moreover, reducing Drp1 activity by Drp1 inhibitor, Mdivi-1, ameliorates both HAP40 overexpression- and ADRM1 depletion-induced mitochondrial dysfunction. Taken together, our studies suggest that HAP40-mediated reduction of ADRM1 alters the mitochondrial fission activity and results in mitochondrial fragmentation and mitochondrial dysfunction. PMID:29209146

Roles of dynamin-related protein 1 in the regulation of mitochondrial fission and apoptosis in response to UV stimuli

Science.gov (United States)

Zhang, Zhenzhen; Feng, Jie; Wu, Shengnan

2011-03-01

Mitochondria are dynamic structures that frequently divide and fuse with one another to form interconnecting network. This network disintegrates into punctiform organelles during apoptosis. However, it remains unclear whether this event has a significant impact on the rate of cell death or only accompanies apoptosis as an epiphenomenon. In this study, we investigate the role of dynamin-related protein 1 (Drp1), a large GTPase that mediates outer mitochondrial membrane fission, in mitochondrial morphology and apoptosis in response to UV irradiation in human lung adenocarcinoma cells (ASTC-a-1) and HeLa cells. Using time-lapse fluorescent imaging, we find that Drp1 primarily distributes in cytosol under physiological conditions. After UV treatment, Drp1 translocates from cytosol to mitochondria, indicating the enhancement of Drp1 mitochondrial accumulation. Down-regulation of Drp1 by shRNA inhibits UV-induced apoptosis. Our results suggest that Drp1 is involved in the regulation of transition from a reticulo-tubular to a punctiform mitochondrial phenotype and mitochondrial fission plays an important role in UV-induced apoptosis.

miR-27 regulates mitochondrial networks by directly targeting the mitochondrial fission factor.

Science.gov (United States)

Tak, Hyosun; Kim, Jihye; Jayabalan, Aravinth Kumar; Lee, Heejin; Kang, Hoin; Cho, Dong-Hyung; Ohn, Takbum; Nam, Suk Woo; Kim, Wook; Lee, Eun Kyung

2014-11-28

Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.

Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner

DEFF Research Database (Denmark)

Halling, Jens Frey; Jørgensen, Stine Ringholm; Olesen, Jesper

2017-01-01

Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effect...... evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner....

Tributyltin induces mitochondrial fission through Mfn1 degradation in human induced pluripotent stem cells.

Science.gov (United States)

Yamada, Shigeru; Asanagi, Miki; Hirata, Naoya; Itagaki, Hiroshi; Sekino, Yuko; Kanda, Yasunari

2016-08-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT is also known to cause various forms of cytotoxicity, including neurotoxicity and immunotoxicity. However, TBT toxicity has not been identified in normal stem cells. In the present study, we examined the effects of TBT on cell growth in human induced pluripotent stem cells (iPSCs). We found that exposure to nanomolar concentrations of TBT decreased intracellular ATP levels and inhibited cell viability in iPSCs. Because TBT suppressed energy production, which is a critical function of the mitochondria, we further assessed the effects of TBT on mitochondrial dynamics. Staining with MitoTracker revealed that nanomolar concentrations of TBT induced mitochondrial fragmentation. TBT also reduced the expression of mitochondrial fusion protein mitofusin 1 (Mfn1), and this effect was abolished by knockdown of the E3 ubiquitin ligase membrane-associated RING-CH 5 (MARCH5), suggesting that nanomolar concentrations of TBT could induce mitochondrial dysfunction via MARCH5-mediated Mfn1 degradation in iPSCs. Thus, mitochondrial function in normal stem cells could be used to assess cytotoxicity associated with metal exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

Energy Technology Data Exchange (ETDEWEB)

Almeida, Luciana O.; Goto, Renata N. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Neto, Marinaldo P.C. [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Sousa, Lucas O. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

2015-03-06

We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

Inhibition of peroxisome fission, but not mitochondrial fission, increases yeast chronological lifespan

NARCIS (Netherlands)

Lefevre, Sophie D; Kumar, Sanjeev; van der Klei, Ida J

2015-01-01

Mitochondria are key players in ageing and cell death. It has been suggested that mitochondrial fragmentation, mediated by the Dnm1/Fis1 organelle fission machinery, stimulates ageing and cell death. This was based on the observation that Saccharomyces cerevisiae Δdnm1 and Δfis1 mutants show an

Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats

International Nuclear Information System (INIS)

Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing; Cai, Zongwei; Dong, Chuan

2015-01-01

Highlights: • PM 2.5 induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease

Mitochondrial fission proteins regulate programmed cell death in yeast

OpenAIRE

Fannjiang, Yihru; Cheng, Wen-Chih; Lee, Sarah J.; Qi, Bing; Pevsner, Jonathan; McCaffery, J. Michael; Hill, R. Blake; Basañez, Gorka; Hardwick, J. Marie

2004-01-01

The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we fo...

Mitochondrial Dynamics Decrease Prior to Axon Degeneration Induced by Vincristine and are Partially Rescued by Overexpressed cytNmnat1.

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Gregory Berbusse

2016-07-01

Full Text Available Axon degeneration is a prominent feature of various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, and is often characterized by aberrant mitochondrial dynamics. Mitochondrial fission, fusion, and motility have been shown to be particularly important in progressive neurodegeneration. Thus we investigated these imperative dynamics, as well as mitochondrial fragmentation in vincristine induced axon degradation in cultured DRG neurons. CytNmnat1 inhibits axon degeneration in various paradigms including vincristine toxicity. The mechanism of its protection is not yet fully understood; therefore, we also investigated the effect of cytNmnat1 on mitochondrial dynamics in vincristine treated neurons. We observed that vincristine treatment decreases the rate of mitochondrial fission, fusion and motility and induces mitochondrial fragmentation. These mitochondrial events precede visible axon degeneration. Overexpression of cytNmnat1 inhibits axon degeneration and preserves the normal mitochondrial dynamics and motility in vincristine treated neurons. We suggest the alterations in mitochondrial structure and dynamics are early events which lead to axon degeneration and cytNmnat1 blocks axon degeneration by halting the vincristine induced changes to mitochondrial structure and dynamics.

Mitochondrial damage: An important mechanism of ambient PM{sub 2.5} exposure-induced acute heart injury in rats

Energy Technology Data Exchange (ETDEWEB)

Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China); Cai, Zongwei, E-mail: zwcai@hkbu.edu.hk [State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR (China); Dong, Chuan, E-mail: dc@sxu.edu.cn [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China)

2015-04-28

Highlights: • PM{sub 2.5} induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM{sub 2.5}) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM{sub 2.5}-induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM{sub 2.5} with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM{sub 2.5} exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM{sub 2.5} exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na{sup +}K{sup +}-ATPase and Ca{sup 2+}-ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM{sub 2.5}-induced heart injury, and may have relations with cardiovascular disease.

Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

Directory of Open Access Journals (Sweden)

Rosalba ePutti

2016-01-01

Full Text Available It has been suggested that skeletal muscle mitochondria play a key role in high fat diet induced insulin resistance. Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle insulin resistance. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to insulin resistance. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of insulin resistance. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift towards mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and insulin resistance development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle insulin resistance and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle insulin resistance, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance.

Mitochondrial fission promotes cell migration by Ca2+ /CaMKII/ERK/FAK pathway in hepatocellular carcinoma.

Science.gov (United States)

Sun, Xiacheng; Cao, Haiyan; Zhan, Lei; Yin, Chun; Wang, Gang; Liang, Ping; Li, Jibin; Wang, Zhe; Liu, Bingrong; Huang, Qichao; Xing, Jinliang

2018-07-01

Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumour cells remained largely unknown. In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of hepatocellular carcinoma when compared to primary hepatocellular carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of hepatocellular carcinoma patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca 2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signalling in hepatocellular carcinoma cells and had a potential treatment effect for hepatocellular carcinoma metastasis in vivo. Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of hepatocellular carcinoma cell migration, which provides strong evidence for this process as a drug target in hepatocellular carcinoma metastasis treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy.

Science.gov (United States)

Zhao, Qingdong; Ye, Mingxia; Yang, Wen; Wang, Min; Li, Mingxia; Gu, Chenglei; Zhao, Luyang; Zhang, Zhe; Han, Weidong; Fan, Wensheng; Meng, Yuanguang

2018-01-01

Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay. Gain of function assay about Mst1 was conducted via adenovirus over-expression. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment and immunofluorescence of HtrA2/Omi. The mitophagy activity were examined via western blots and immunofluorescence. First, we found that Mst1 was significantly downregulated in the ectopic endometrium of endometriosis compared to the normal endometrium. However, the recovery of Mst1 function was closely associated with the inability of endometrial stromal cells (ESCs) to migrate and survive. A functional study indicated that regaining Mst1 enhanced Drp1 post-transcriptional phosphorylation at Ser616 and repressed Parkin transcription activity via p53, leading to mitochondrial fission activation and mitophagy inhibition. Excessive Drp1-related fission forced the mitochondria to liberate HtrA2/Omi into the cytoplasm. Moreover, Mst1-induced defective mitophagy evoked cellular oxidative stress, energy metabolism and calcium overload. Through excessive mitochondrial fission and aberrant mitophagy, Mst1 launched caspase 9-related mitochondrial apoptosis and abrogated F-actin/lamellipodium-dependent cellular migration. Notably, we also defined NR4A/miR181c as the upstream signal for Mst1 dysfunction in endometriosis. Collectively, our results comprehensively described the important role of the NR4A-miR181c-Mst1 pathway in endometriosis, which handled mitochondrial

Defects in mitochondrial fission protein dynamin-related protein 1 are linked to apoptotic resistance and autophagy in a lung cancer model.

Directory of Open Access Journals (Sweden)

Kelly Jean Thomas

Full Text Available Evasion of apoptosis is implicated in almost all aspects of cancer progression, as well as treatment resistance. In this study, resistance to apoptosis was identified in tumorigenic lung epithelial (A549 cells as a consequence of defects in mitochondrial and autophagic function. Mitochondrial function is determined in part by mitochondrial morphology, a process regulated by mitochondrial dynamics whereby the joining of two mitochondria, fusion, inhibits apoptosis while fission, the division of a mitochondrion, initiates apoptosis. Mitochondrial morphology of A549 cells displayed an elongated phenotype-mimicking cells deficient in mitochondrial fission protein, Dynamin-related protein 1 (Drp1. A549 cells had impaired Drp1 mitochondrial recruitment and decreased Drp1-dependent fission. Cytochrome c release and caspase-3 and PARP cleavage were impaired both basally and with apoptotic stimuli in A549 cells. Increased mitochondrial mass was observed in A549 cells, suggesting defects in mitophagy (mitochondrial selective autophagy. A549 cells had decreased LC3-II lipidation and lysosomal inhibition suggesting defects in autophagy occur upstream of lysosomal degradation. Immunostaining indicated mitochondrial localized LC3 punctae in A549 cells increased after mitochondrial uncoupling or with a combination of mitochondrial depolarization and ectopic Drp1 expression. Increased inhibition of apoptosis in A549 cells is correlated with impeded mitochondrial fission and mitophagy. We suggest mitochondrial fission defects contribute to apoptotic resistance in A549 cells.

Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: kanda@nihs.go.jp [Division of Pharmacology, National Institute of Health Sciences (Japan)

2016-02-05

Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

International Nuclear Information System (INIS)

Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

2016-01-01

Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

Neutron-induced fission cross sections

International Nuclear Information System (INIS)

Weigmann, H.

1991-01-01

In the history of fission research, neutron-induced fission has always played the most important role. The practical importance of neutron-induced fission rests upon the fact that additional neutrons are produced in the fission process, and thus a chain reaction becomes possible. The practical applications of neutron-induced fission will not be discussed in this chapter, but only the physical properties of one of its characteristics, namely (n,f) cross sections. The most important early summaries on the subject are the monograph edited by Michaudon which also deals with the practical applications, the earlier review article on fission by Michaudon, and the review by Bjornholm and Lynn, in which neutron-induced fission receives major attention. This chapter will attempt to go an intermediate way between the very detailed theoretical treatment in the latter review and the cited monograph which emphasizes the applied aspects and the techniques of fission cross-section measurements. The more recent investigations in the field will be included. Section II will survey the properties of cross sections for neutron-induced fission and also address some special aspects of the experimental methods applied in their measurement. Section Ill will deal with the formal theory of neutron-induced nuclear reactions for the resolved resonance region and the region of statistical nuclear reactions. In Section IV, the fission width, or fission transmission coefficient, will be discussed in detail. Section V will deal with the broader structures due to incompletely damped vibrational resonances, and in particular will address the special case of thorium and neighboring isotopes. Finally, Section VI will briefly discuss parity violation effects in neutron-induced fission. 74 refs., 14 figs., 3 tabs

Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

Science.gov (United States)

Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

2017-09-01

Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

Directory of Open Access Journals (Sweden)

Susana Rovira-Llopis

2017-04-01

Full Text Available Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1, mitofusin-2 (MFN2 and optic atrophy (OPA-1, while fission is controlled by mitochondrial fission 1 (FIS1, dynamin-related protein 1 (DRP1 and mitochondrial fission factor (MFF. PARKIN and (PTEN-induced putative kinase 1 (PINK1 participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1, dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.

Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

Energy Technology Data Exchange (ETDEWEB)

Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

2014-07-11

Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

Directory of Open Access Journals (Sweden)

Khushbu Jain

2015-01-01

Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis.

Science.gov (United States)

Zhou, Hao; Zhang, Ying; Hu, Shunying; Shi, Chen; Zhu, Pingjun; Ma, Qiang; Jin, Qinhua; Cao, Feng; Tian, Feng; Chen, Yundai

2017-08-01

The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic, and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow, and lower microcirculation perfusion defects. Histological analysis showed that cardiac microcirculation endothelial cells (CMEC) in melatonin-treated mice had an unbroken endothelial barrier, increased endothelial nitric oxide synthase expression, unobstructed lumen, reduced inflammatory cell infiltration, and less endothelial damage. In contrast, AMP-activated protein kinase α (AMPKα) deficiency abolished the beneficial effects of melatonin on microvasculature. In vitro, IRI activated dynamin-related protein 1 (Drp1)-dependent mitochondrial fission, which subsequently induced voltage-dependent anion channel 1 (VDAC1) oligomerization, hexokinase 2 (HK2) liberation, mitochondrial permeability transition pore (mPTP) opening, PINK1/Parkin upregulation, and ultimately mitophagy-mediated CMEC death. However, melatonin strengthened CMEC survival via activation of AMPKα, followed by p-Drp1 S616 downregulation and p-Drp1 S37 upregulation, which blunted Drp1-dependent mitochondrial fission. Suppression of mitochondrial fission by melatonin recovered VDAC1-HK2 interaction that prevented mPTP opening and PINK1/Parkin activation, eventually blocking mitophagy-mediated cellular death. In summary, this study confirmed that melatonin protects cardiac microvasculature against IRI. The underlying mechanism may be attributed to the inhibitory effects of melatonin on mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis via activation

Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways.

Science.gov (United States)

Rival, Thomas; Macchi, Marc; Arnauné-Pelloquin, Laetitia; Poidevin, Mickael; Maillet, Frédéric; Richard, Fabrice; Fatmi, Ahmed; Belenguer, Pascale; Royet, Julien

2011-03-01

Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent.

Muon-induced fission

International Nuclear Information System (INIS)

Polikanov, S.

1980-01-01

A review of recent experimental results on negative-muon-induced fission, both of 238 U and 232 Th, is given. Some conclusions drawn by the author are concerned with muonic atoms of fission fragments and muonic atoms of the shape isomer of 238 U. (author)

The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process

International Nuclear Information System (INIS)

Park, Jeehye; Lee, Gina; Chung, Jongkyeong

2009-01-01

The two Parkinson's disease (PD) genes, PTEN-induced kinase 1 (PINK1) and parkin, are linked in a common pathway which affects mitochondrial integrity and function. However, it is still not known what this pathway does in the mitochondria. Therefore, we investigated its physiological function in Drosophila. Because Drosophila PINK1 and parkin mutants show changes in mitochondrial morphology in both indirect flight muscles and dopaminergic neurons, we here investigated whether the PINK1-Parkin pathway genetically interacts with the regulators of mitochondrial fusion and fission such as Drp1, which promotes mitochondrial fission, and Opa1 or Marf, which induces mitochondrial fusion. Surprisingly, DrosophilaPINK1 and parkin mutant phenotypes were markedly suppressed by overexpression of Drp1 or downregulation of Opa1 or Marf, indicating that the PINK1-Parkin pathway regulates mitochondrial remodeling process in the direction of promoting mitochondrial fission. Therefore, we strongly suggest that mitochondrial fusion and fission process could be a prominent therapeutic target for the treatment of PD.

Nuclear fission and neutron-induced fission cross-sections

Energy Technology Data Exchange (ETDEWEB)

James, G.D.; Lynn, J.E.; Michaudon, A.; Rowlands, J.; de Saussure, G.

1981-01-01

A general presentation of current knowledge of the fission process is given with emphasis on the low energy fission of actinide nuclei and neutron induced fission. The need for and the required accuracy of fission cross section data in nuclear energy programs are discussed. A summary is given of the steps involved in fission cross section measurement and the range of available techniques. Methods of fission detection are described with emphasis on energy dependent changed and detector efficiency. Examples of cross section measurements are given and data reduction is discussed. The calculation of fission cross sections is discussed and relevant nuclear theory including the formation and decay of compound nuclei and energy level density is introduced. A description of a practical computation of fission cross sections is given.

Tributyltin induces mitochondrial fission through NAD-IDH dependent mitofusin degradation in human embryonic carcinoma cells.

Science.gov (United States)

Yamada, Shigeru; Kotake, Yaichiro; Nakano, Mizuho; Sekino, Yuko; Kanda, Yasunari

2015-08-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT acts at the nanomolar level through genomic pathways via the peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR). We recently reported that TBT inhibits cell growth and the ATP content in the human embryonic carcinoma cell line NT2/D1 via a non-genomic pathway involving NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which metabolizes isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we evaluated the effects of TBT on mitochondrial NAD-IDH and energy production. Staining with MitoTracker revealed that nanomolar TBT levels induced mitochondrial fragmentation. TBT also degraded the mitochondrial fusion proteins, mitofusins 1 and 2. Interestingly, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. Incubation with an α-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Our data suggest that nanomolar TBT levels impair mitochondrial quality control via NAD-IDH in NT2/D1 cells. Thus, mitochondrial function in embryonic cells could be used to assess cytotoxicity associated with metal exposure.

Mitochondrial fission determines cisplatin sensitivity in tongue squamous cell carcinoma through the BRCA1–miR-593-5p–MFF axis

Science.gov (United States)

Chen, Weixiong; Chen, Weiliang; Tang, Qionglan; Wang, Youyuan; Su, Yuxiong; Jin, Shaowen; Zhang, Daming; Zhong, Jianglong; Li, Yilin; Wen, Bin; Zhang, Zhang; Yang, Pu; Zhou, Bin; Liang, Qixiang; Yu, Xing; Zhu, Yinghua; Hu, Pengnan; Chu, Junjun; Huang, Wei; Feng, Yuhuan; Peng, Hongzhuang; Huang, Qihong; Song, Erwei; Li, Jinsong

2015-01-01

Cisplatin has been widely employed as a cornerstone chemotherapy treatment for a wide spectrum of solid neoplasms; increasing tumor responsiveness to cisplatin has been a topic of interest for the past 30 years. Strong evidence has indicated that mitochondrial fission participates in the regulation of apoptosis in many diseases; however, whether mitochondrial fission regulates cisplatin sensitivity remains poorly understood. Here, we show that MFF mediated mitochondrial fission and apoptosis in tongue squamous cell carcinoma (TSCC) cells after cisplatin treatment and that miR-593-5p was downregulated in this process. miR-593-5p attenuated mitochondrial fission and cisplatin sensitivity by targeting the 3′ untranslated region sequence of MFF and inhibiting its translation. In exploring the underlying mechanism of miR-593-5p downregulation, we observed that BRCA1 transactivated miR-593-5p expression and attenuated cisplatin sensitivity in vitro. The BRCA1-miR-593-5p-MFF axis also affected cisplatin sensitivity in vivo. Importantly, in a retrospective analysis of multiple centers, we further found that the BRCA1-miR-593-5p-MFF axis was significantly associated with cisplatin sensitivity and the survival of patients with TSCC. Together, our data reveal a model for mitochondrial fission regulation at the transcriptional and post-transcriptional levels; we also reveal a new pathway for BRCA1 in determining cisplatin sensitivity through the mitochondrial fission program. PMID:25912308

Mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease

OpenAIRE

Ong, Sang-Bing; Kalkhoran, Siavash Beikoghli; Cabrera-Fuentes, Hector A.; Hausenloy, Derek?J.

2015-01-01

The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movement impact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangeme...

Induced-Fission Imaging of Nuclear Material

International Nuclear Information System (INIS)

Hausladen, Paul; Blackston, Matthew A.; Mullens, James Allen; McConchie, Seth M.; Mihalczo, John T.; Bingham, Philip R.; Ericson, Milton Nance; Fabris, Lorenzo

2010-01-01

This paper presents initial results from development of the induced-fission imaging technique, which can be used for the purpose of measuring or verifying the distribution of fissionable material in an unopened container. The technique is based on stimulating fissions in nuclear material with 14 MeV neutrons from an associated-particle deuterium-tritium (D-T) generator and counting the subsequent induced fast fission neutrons with an array of fast organic scintillation detectors. For each source neutron incident on the container, the neutron creation time and initial trajectory are known from detection of the associated alpha particle of the d + t → α + n reaction. Many induced fissions will lie along (or near) the interrogating neutron path, allowing an image of the spatial distribution of prompt induced fissions, and thereby fissionable material, to be constructed. A variety of induced-fission imaging measurements have been performed at Oak Ridge National Laboratory with a portable, low-dose D-T generator, including single-view radiographic measurements and three-dimensional tomographic measurements. Results from these measurements will be presented along with the neutron transmission images that have been performed simultaneously. This new capability may have applications to a number of areas in which there may be a need to confirm the presence or configuration of nuclear materials, such as nuclear material control and accountability, quality assurance, treaty confirmation, or homeland security applications.

Mitochondrial localization of fission yeast manganese superoxide dismutase is required for its lysine acetylation and for cellular stress resistance and respiratory growth

International Nuclear Information System (INIS)

Takahashi, Hidekazu; Suzuki, Takehiro; Shirai, Atsuko; Matsuyama, Akihisa; Dohmae, Naoshi; Yoshida, Minoru

2011-01-01

Research highlights: → Fission yeast manganese superoxide dismutase (MnSOD) is acetylated. → The mitochondrial targeting sequence (MTS) is required for the acetylation of MnSOD. → The MTS is not crucial for MnSOD activity, but is important for respiratory growth. → Posttranslational regulation of MnSOD differs between budding and fission yeast. -- Abstract: Manganese-dependent superoxide dismutase (MnSOD) is localized in the mitochondria and is important for oxidative stress resistance. Although transcriptional regulation of MnSOD has been relatively well studied, much less is known about the protein's posttranslational regulation. In budding yeast, MnSOD is activated after mitochondrial import by manganese ion incorporation. Here we characterize posttranslational modification of MnSOD in the fission yeast Schizosaccharomyces pombe. Fission yeast MnSOD is acetylated at the 25th lysine residue. This acetylation was diminished by deletion of N-terminal mitochondrial targeting sequence, suggesting that MnSOD is acetylated after import into mitochondria. Mitochondrial localization of MnSOD is not essential for the enzyme activity, but is crucial for oxidative stress resistance and growth under respiratory conditions of fission yeast. These results suggest that, unlike the situation in budding yeast, S. pombe MnSOD is already active even before mitochondrial localization; nonetheless, mitochondrial localization is critical to allow the cell to cope with reactive oxygen species generated inside or outside of mitochondria.

Mitochondrial morphology and cardiovascular disease

OpenAIRE

Ong, Sang-Bing; Hausenloy, Derek J.

2010-01-01

Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a...

UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

Science.gov (United States)

Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

2016-02-25

The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

The LRRK2 Variant E193K Prevents Mitochondrial Fission Upon MPP+ Treatment by Altering LRRK2 Binding to DRP1

Directory of Open Access Journals (Sweden)

Maria Perez Carrion

2018-02-01

Full Text Available Mutations in leucine-rich repeat kinase 2 gene (LRRK2 are associated with familial and sporadic Parkinson’s disease (PD. LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed the functional and molecular consequences of a novel variant, E193K, identified in an Italian family. E193K substitution does not influence LRRK2 kinase activity. Instead it affects LRRK2 biochemical properties, such as phosphorylation at Ser935 and affinity for 14-3-3ε. Primary fibroblasts obtained from an E193K carrier demonstrated increased cellular toxicity and abnormal mitochondrial fission upon 1-methyl-4-phenylpyridinium treatment. We found that E193K alters LRRK2 binding to DRP1, a crucial mediator of mitochondrial fission. Our data support a role for LRRK2 as a scaffolding protein influencing mitochondrial fission.

Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission

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Gary B. O'Mealey

2017-04-01

Full Text Available The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN, an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1 cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN mitigates the recruitment and/or retention of the soluble fission factor Drp1 to mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials.

Nuclear fission and neutron-induced fission cross-sections

CERN Document Server

James, G D; Michaudon, A; Michaudon, A; Cierjacks, S W; Chrien, R E

2013-01-01

Nuclear Fission and Neutron-Induced Fission Cross-Sections is the first volume in a series on Neutron Physics and Nuclear Data in Science and Technology. This volume serves the purpose of providing a thorough description of the many facets of neutron physics in different fields of nuclear applications. This book also attempts to bridge the communication gap between experts involved in the experimental and theoretical studies of nuclear properties and those involved in the technological applications of nuclear data. This publication will be invaluable to those interested in studying nuclear fis

(d,p)-transfer induced fission of heavy radioactive beams

CERN Document Server

Veselsky, Martin

2012-01-01

(d,p)-transfer induced fission is proposed as a tool to study low energy fission of exotic heavy nuclei. Primary goal is to directly determine the fission barrier height of proton-rich fissile nuclei, preferably using the radio-active beams of isotopes of odd elements, and thus confirm or exclude the low values of fission barrier heights, typically extracted using statistical calculations in the compound nucleus reactions at higher excitation energies. Calculated fission cross sections in transfer reactions of the radioactive beams show sufficient sensitivity to fission barrier height. In the probable case that fission rates will be high enough, mass asymmetry of fission fragments can be determined. Results will be relevant for nuclear astrophysics and for production of super-heavy nuclei. Transfer induced fission offers a possibility for systematic study the low energy fission of heavy exotic nuclei at the ISOLDE.

Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice.

Science.gov (United States)

Cao, Ke; Xu, Jie; Zou, Xuan; Li, Yuan; Chen, Cong; Zheng, Adi; Li, Hao; Li, Hua; Szeto, Ignatius Man-Yau; Shi, Yujie; Long, Jiangang; Liu, Jiankang; Feng, Zhihui

2014-02-01

A Mediterranean diet rich in olive oil has profound influence on health outcomes including metabolic syndrome. However, the active compound and detailed mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic compound in virgin olive oil, has received increased attention for its antioxidative activity and regulation of mitochondrial function. Here, we investigated whether HT is the active compound in olive oil exerting a protective effect against metabolic syndrome. In this study, we show that HT could prevent high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress by enhancing antioxidant enzyme activities, normalize expression of mitochondrial complex subunits and mitochondrial fission marker Drp1, and eventually inhibit apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial carbonyl protein were decreased and mitochondrial complex activities were significantly improved by HT supplementation. In db/db mice, HT significantly decreased fasting glucose, similar to metformin. Notably, HT decreased serum lipid, at which metformin failed. Also, HT was more effective at decreasing the oxidation levels of lipids and proteins in both liver and muscle tissue. Similar to the results in the HFD model, HT decreased muscle mitochondrial carbonyl protein levels and improved mitochondrial complex activities in db/db mice. Our study links the olive oil component HT to diabetes and metabolic disease through changes that are not limited to decreases in oxidative stress, suggesting a potential pharmaceutical or clinical use of HT in metabolic syndrome treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Resveratrol induces mitochondrial biogenesis in endothelial cells.

Science.gov (United States)

Csiszar, Anna; Labinskyy, Nazar; Pinto, John T; Ballabh, Praveen; Zhang, Hanrui; Losonczy, Gyorgy; Pearson, Kevin; de Cabo, Rafael; Pacher, Pal; Zhang, Cuihua; Ungvari, Zoltan

2009-07-01

Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.

Asymmetry in ternary fission induced by polarized neutrons and fission mechanism

International Nuclear Information System (INIS)

Bunakov, V.E.; Gennenvajn, F.; Dzhessinger, P.; Mutterer, M.; Petrov, G.A.

2003-01-01

The results of measuring the P-odd, P-even (right-left) and T-odd asymmetries of the charged particles emission in the double and ternary fission, induced by the polarized neutrons, are considered. It is shown, what kind of information on the mechanism of the ternary nuclear fission may be obtained from the theoretical analysis of these data [ru

Nuclear dynamics in heavy ion induced fusion-fission reactions

International Nuclear Information System (INIS)

Kapoor, S.S.

1992-01-01

Heavy ion induced fission and fission-like reactions evolve through a complex nuclear dynamics encountered in the medium energy nucleus-nucleus collisions. In the recent years, measurements of the fragment-neutron and fragment-charged particle angular correlations in heavy ion induced fusion-fission reactions, have provided new information on the dynamical times of nuclear deformations of the initial dinuclear complex to the fission saddle point and the scission point. From the studies of fragment angular distributions in heavy ion induced fission it has been possible to infer the relaxation times of the dinuclear complex in the K-degree of freedom and our recent measurements on the entrance channel dependence of fragment anisotropies have provided an experimental signature of the presence of fissions before K-equilibration. This paper reviews recent experimental and theoretical status of the above studies with particular regard to the questions relating to dynamical times, nuclear dissipation and the effect of nuclear dissipation on the K-distributions at the fission saddle in completely equilibrated compound nucleus. (author). 19 refs., 9 figs

Mitochondrial shaping cuts.

Science.gov (United States)

Escobar-Henriques, Mafalda; Langer, Thomas

2006-01-01

A broad range of cellular processes are regulated by proteolytic events. Proteolysis has now also been established to control mitochondrial morphology which results from the balanced action of fusion and fission. Two out of three known core components of the mitochondrial fusion machinery are under proteolytic control. The GTPase Fzo1 in the outer membrane of mitochondria is degraded along two independent proteolytic pathways. One controls mitochondrial fusion in vegetatively growing cells, the other one acts upon mating factor-induced cell cycle arrest. Fusion also depends on proteolytic processing of the GTPase Mgm1 by the rhomboid protease Pcp1 in the inner membrane of mitochondria. Functional links of AAA proteases or other proteolytic components to mitochondrial dynamics are just emerging. This review summarises the current understanding of regulatory roles of proteolytic processes for mitochondrial plasticity.

Actinide neutron-induced fission up to 20 MeV

International Nuclear Information System (INIS)

Maslov, V.M.

2001-01-01

Fission and total level densities modelling along with double-humped fission barrier parameters allow to describe available actinide neutron-induced fission cross section data in the incident neutron energy range of ∼ 10 keV - 20 MeV. Saddle asymmetries relevant to shell correction model calculations influence fission barriers, extracted by cross section data analysis. The inner barrier was assumed axially symmetric in case of U, Np and Pu neutron-deficient nuclei. It is shown that observed irregularities in neutron-induced fission cross section data in the energy range of 0.5-3 MeV could be attributed to the interplay of few-quasiparticle excitations in the level density of fissioning and residual nuclei. Estimates of first-chance fission cross section and secondary neutron spectrum model were validated by 238 U fission, (n,2n) and (n,3n) data description up to 20 MeV. (author)

Actinide neutron-induced fission up to 20 MeV

Energy Technology Data Exchange (ETDEWEB)

Maslov, V M [Radiation Physics and Chemistry Problems Institute, Minsk-Sosny (Belarus)

2001-12-15

Fission and total level densities modelling along with double-humped fission barrier parameters allow to describe available actinide neutron-induced fission cross section data in the incident neutron energy range of {approx} 10 keV - 20 MeV. Saddle asymmetries relevant to shell correction model calculations influence fission barriers, extracted by cross section data analysis. The inner barrier was assumed axially symmetric in case of U, Np and Pu neutron-deficient nuclei. It is shown that observed irregularities in neutron-induced fission cross section data in the energy range of 0.5-3 MeV could be attributed to the interplay of few-quasiparticle excitations in the level density of fissioning and residual nuclei. Estimates of first-chance fission cross section and secondary neutron spectrum model were validated by {sup 238}U fission, (n,2n) and (n,3n) data description up to 20 MeV. (author)

Mechanism of neuroprotective mitochondrial remodeling by PKA/AKAP1.

Directory of Open Access Journals (Sweden)

Ronald A Merrill

2011-04-01

Full Text Available Mitochondrial shape is determined by fission and fusion reactions catalyzed by large GTPases of the dynamin family, mutation of which can cause neurological dysfunction. While fission-inducing protein phosphatases have been identified, the identity of opposing kinase signaling complexes has remained elusive. We report here that in both neurons and non-neuronal cells, cAMP elevation and expression of an outer-mitochondrial membrane (OMM targeted form of the protein kinase A (PKA catalytic subunit reshapes mitochondria into an interconnected network. Conversely, OMM-targeting of the PKA inhibitor PKI promotes mitochondrial fragmentation upstream of neuronal death. RNAi and overexpression approaches identify mitochondria-localized A kinase anchoring protein 1 (AKAP1 as a neuroprotective and mitochondria-stabilizing factor in vitro and in vivo. According to epistasis studies with phosphorylation site-mutant dynamin-related protein 1 (Drp1, inhibition of the mitochondrial fission enzyme through a conserved PKA site is the principal mechanism by which cAMP and PKA/AKAP1 promote both mitochondrial elongation and neuronal survival. Phenocopied by a mutation that slows GTP hydrolysis, Drp1 phosphorylation inhibits the disassembly step of its catalytic cycle, accumulating large, slowly recycling Drp1 oligomers at the OMM. Unopposed fusion then promotes formation of a mitochondrial reticulum, which protects neurons from diverse insults.

Fusion--fission hybrid concepts for laser-induced fusion

International Nuclear Information System (INIS)

Maniscalco, J.

1976-01-01

Fusion-fission hybrid concepts are viewed as subcritical fission reactors driven and controlled by high-energy neutrons from a laser-induced fusion reactor. Blanket designs encompassing a substantial portion of the spectrum of different fission reactor technologies are analyzed and compared by calculating their fissile-breeding and fusion-energy-multiplying characteristics. With a large number of different fission technologies to choose from, it is essential to identify more promising hybrid concepts that can then be subjected to in-depth studies that treat the engineering safety, and economic requirements as well as the neutronic aspects. In the course of neutronically analyzing and comparing several fission blanket concepts, this work has demonstrated that fusion-fission hybrids can be designed to meet a broad spectrum of fissile-breeding and fusion-energy-multiplying requirements. The neutronic results should prove to be extremely useful in formulating the technical scope of future studies concerned with evaluating the technical and economic feasibility of hybrid concepts for laser-induced fusion

The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations.

Science.gov (United States)

Barbosa, Daniel José; Serrat, Romàn; Mirra, Serena; Quevedo, Martí; de Barreda, Elena Goméz; Àvila, Jesús; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Lourdes Bastos, Maria de; Capela, João Paulo; Soriano, Eduardo; Carvalho, Félix

2014-06-01

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca(2+) homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury.

Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

International Nuclear Information System (INIS)

Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

2014-01-01

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS

Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

2014-05-01

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin

Determination of the fission barrier height in fission of heavy radioactive beams induced by the (d,p)-transfer

CERN Multimedia

A theoretical framework is described, allowing to determine the fission barrier height using the observed cross sections of fission induced by the (d,p)-transfer with accuracy, which is not achievable in another type of low-energy fission of neutron-deficient nuclei, the $\\beta$-delayed fission. The primary goal is to directly determine the fission barrier height of proton-rich fissile nuclei, preferably using the radio-active beams of isotopes of odd elements, and thus confirm or exclude the low values of fission barrier heights, typically extracted using statistical calculations in the compound nucleus reactions at higher excitation energies. Calculated fission cross sections in transfer reactions of the radioactive beams show sufficient sensitivity to fission barrier height. In the probable case that fission rates will be high enough, mass asymmetry of fission fragments can be determined. Results will be relevant for nuclear astrophysics and for production of super-heavy nuclei. Transfer induced fission of...

Measurement of prompt fission gamma-ray spectra in fast neutron-induced fission

International Nuclear Information System (INIS)

Laborie, J.M.; Belier, G.; Taieb, J.

2012-01-01

Knowledge of prompt fission gamma-ray emission has been of major interest in reactor physics for a few years. Since very few experimental spectra were ever published until now, new measurements would be also valuable to improve our understanding of the fission process. An experimental method is currently being developed to measure the prompt fission gamma-ray spectrum from some tens keV up to 10 MeV at least. The mean multiplicity and total energy could be deduced. In this method, the gamma-rays are measured with a bismuth germanate (BGO) detector which has the advantage to present a high P/T ratio and a high efficiency compared to other gamma-ray detectors. The prompt fission neutrons are rejected by the time of flight technique between the BGO detector and a fission trigger given by a fission chamber or a scintillating active target. Energy and efficiency calibration of the BGO detector were carried out up to 10.76 MeV by means of the Al-27(p, gamma) reaction. First prompt fission gamma-ray spectrum measurements performed for the spontaneous fission of Cf-252 and for 1.7 and 15.6 MeV neutron-induced fission of U-238 at the CEA, DAM, DIF Van de Graaff accelerator, will be presented. (authors)

Muon induced fission and fission track dating of minerals

International Nuclear Information System (INIS)

Marques, A.

1988-01-01

The effects of muon induced fission on geological dating of samples by the fission track method are evaluated for the case of muscovite minerals. It is found a small but significant effect, greater for the longer ages. Since calculations are developped under the hypothesis of constant atmosphere and primary cosmic ray flux it is suggested that any discrepancy found in ages of very old material that cannot be accounted for by well known environmental influences, be taken as an indication of variation on either the atmospheric stopping power or the intensity of cosmic radiation along the ages. (author) [pt

Ternary fission induced by polarized neutrons

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Gönnenwein Friedrich

2013-12-01

Full Text Available Ternary fission of (e,e U- and Pu- isotopes induced by cold polarized neutrons discloses some new facets of the process. In the so-called ROT effect shifts in the angular distributions of ternary particles relative to the fission fragments show up. In the so-called TRI effect an asymmetry in the emission of ternary particles relative to a plane formed by the fragment momentum and the spin of the neutron appear. The two effects are shown to be linked to the components of angular momentum perpendicular and parallel to the fission axis at the saddle point of fission. Based on theoretical models the spectroscopic properties of the collective transitional states at the saddle point are inferred from experiment.

Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta.

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Marc Liesa

Full Text Available There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression.Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1beta is associated with a selective reduction in Mitofusin 2 (Mfn2 expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1beta increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1beta-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1beta increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor alpha (ERRalpha.Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1beta in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2.

Recent advances in heavy-ion-induced fission

International Nuclear Information System (INIS)

Plasil, F.

1984-01-01

Three topics are discussed. The first deals with results that have been published recently on angular-momentum-dependent fission barriers. They are discussed because of the significance that we attach to them. We feel that, after a decade of study and controversy, we have arrived at a quantitative understanding of the competition between heavy-ion-induced fission and particle emission from compound nuclei at relatively low bombarding energies. The second topic concerns the extension of our heavy-ion-induced fission studies to higher energies. It is clear that in this regime the effects, both of fission following incomplete fusion and of extra-push requirements, need to be considered. Finally, discussed are our recent conclusions concerning the fissionlike decay of products from reactions between two 58 Ni nuclei at an incident energy, E/A, of 15.3 MeV, as well as the impact of our findings on the conclusions drawn from previous, similar measurements. 39 references

DJ-1 KNOCK-DOWN IMPAIRS ASTROCYTE MITOCHONDRIAL FUNCTION

Science.gov (United States)

LARSEN, N. J.; AMBROSI, G.; MULLETT, S. J.; BERMAN, S. B.; HINKLE, D. A.

2012-01-01

Mitochondrial dysfunction has long been implicated in the pathogenesis of Parkinson’s disease (PD). PD brain tissues show evidence for mitochondrial respiratory chain Complex I deficiency. Pharmacological inhibitors of Complex I, such as rotenone, cause experimental parkinsonism. The cytoprotective protein DJ-1, whose deletion is sufficient to cause genetic PD, is also known to have mitochondria-stabilizing properties. We have previously shown that DJ-1 is over-expressed in PD astrocytes, and that DJ-1 deficiency impairs the capacity of astrocytes to protect co-cultured neurons against rotenone. Since DJ-1 modulated, astrocyte-mediated neuroprotection against rotenone may depend upon proper astrocytic mitochondrial functioning, we hypothesized that DJ-1 deficiency would impair astrocyte mitochondrial motility, fission/fusion dynamics, membrane potential maintenance, and respiration, both at baseline and as an enhancement of rotenone-induced mitochondrial dysfunction. In astrocyte-enriched cultures, we observed that DJ-1 knock-down reduced mitochondrial motility primarily in the cellular processes of both untreated and rotenone treated cells. In these same cultures, DJ-1 knock-down did not appreciably affect mitochondrial fission, fusion, or respiration, but did enhance rotenone-induced reductions in the mitochondrial membrane potential. In neuron–astrocyte co-cultures, astrocytic DJ-1 knock-down reduced astrocyte process mitochondrial motility in untreated cells, but this effect was not maintained in the presence of rotenone. In the same co-cultures, astrocytic DJ-1 knock-down significantly reduced mitochondrial fusion in the astrocyte cell bodies, but not the processes, under the same conditions of rotenone treatment in which DJ-1 deficiency is known to impair astrocyte-mediated neuroprotection. Our studies therefore demonstrated the following new findings: (i) DJ-1 deficiency can impair astrocyte mitochondrial physiology at multiple levels, (ii) astrocyte

MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

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Elisa Balboa

2017-08-01

Full Text Available MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

Nuclear fission induced by heavy ions

International Nuclear Information System (INIS)

Newton, J.O.

1988-09-01

Because the accelerators of the 50's and 60's mostly provided beams of light ions, well suited for studying individual quantum states of low angular momentum or reactions involving the transfer of one or two nucleons, the study of fission, being an example of large-scale collective motion, has until recently been outside of the mainstream of nuclear research. This situation has changed in recent years, due to the new generation of accelerators capable of producing beams of heavy ions with energies high enough to overcome the Coulomb barriers of all stable nuclei. These have made possible the study of new examples of large-scale collective motions, involving major rearrangements of nuclear matter, such as deep-inelastic collisions and heavy-ion fusion. Perhaps the most exciting development in the past few years is the discovery that dissipative effects (nuclear viscosity) play an important role in fission induced by heavy ions, contrary to earlier assumptions that the viscosity involved in fission was very weak and played only a minor role. This review will be mainly concerned with developments in heavy-ion induced fission during the last few years and have an emphasis on the very recent results on dissipative effects. Since heavy-ion bombardment usually results in compound systems with high excitation energies and angular momenta, shell effects might be expected to be small, and the subject of low energy fission, where they are important, will not be addressed. 285 refs., 58 figs

Strenuous exercise induces mitochondrial damage in skeletal muscle of old mice

International Nuclear Information System (INIS)

Lee, Sangho; Kim, Minjung; Lim, Wonchung; Kim, Taeyoung; Kang, Chounghun

2015-01-01

Strenuous exercise is known to cause excessive ROS generation and inflammation. However, the mechanisms responsible for the regulation of mitochondrial integrity in the senescent muscle during high-intensity exercise (HE) are not well studied. Here, we show that HE suppresses up-regulation of mitochondrial function despite increase in mitochondrial copy number, following excessive ROS production, proinflammatory cytokines and NFκB activation. Moreover, HE in the old group resulted in the decreasing of both fusion (Mfn2) and fission (Drp1) proteins that may contribute to alteration of mitochondrial morphology. This study suggests that strenuous exercise does not reverse age-related mitochondrial damage and dysfunction by the increased ROS and inflammation. - Highlights: • Effect of exercise on mitochondrial function of aged skeletal muscles was studied. • Strenuous exercise triggered excessive ROS production and inflammatory cytokines. • Strenuous exercise suppressed mitochondrial function in senescent muscle

Strenuous exercise induces mitochondrial damage in skeletal muscle of old mice

Energy Technology Data Exchange (ETDEWEB)

Lee, Sangho; Kim, Minjung [Department of Physical Education, Hankuk Univrsity of Foreign Studies, Seoul 130-791 (Korea, Republic of); Lim, Wonchung [Department of Sports Medicine, College of Health Science, Cheongju University, Cheongju 363-764 (Korea, Republic of); Kim, Taeyoung [Department of Physical Education, Hankuk Univrsity of Foreign Studies, Seoul 130-791 (Korea, Republic of); Kang, Chounghun, E-mail: kangx119@umn.edu [Department of Physical Education, Hankuk Univrsity of Foreign Studies, Seoul 130-791 (Korea, Republic of); Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota at Twin Cities, Minneapolis, MN 55455 (United States)

2015-05-29

Strenuous exercise is known to cause excessive ROS generation and inflammation. However, the mechanisms responsible for the regulation of mitochondrial integrity in the senescent muscle during high-intensity exercise (HE) are not well studied. Here, we show that HE suppresses up-regulation of mitochondrial function despite increase in mitochondrial copy number, following excessive ROS production, proinflammatory cytokines and NFκB activation. Moreover, HE in the old group resulted in the decreasing of both fusion (Mfn2) and fission (Drp1) proteins that may contribute to alteration of mitochondrial morphology. This study suggests that strenuous exercise does not reverse age-related mitochondrial damage and dysfunction by the increased ROS and inflammation. - Highlights: • Effect of exercise on mitochondrial function of aged skeletal muscles was studied. • Strenuous exercise triggered excessive ROS production and inflammatory cytokines. • Strenuous exercise suppressed mitochondrial function in senescent muscle.

A position sensitive parallel plate avalanche fission detector for use in particle induced fission coincidence measurements

NARCIS (Netherlands)

Plicht, J. van der

1980-01-01

A parallel plate avalanche detector developed for the detection of fission fragments in particle induced fission reactions is described. The active area is 6 × 10 cm2; it is position sensitive in one dimension with a resolution of 2.5 mm. The detector can withstand a count rate of 25000 fission

Study of transfer induced fission and fusion-fission reactions for 28 Si + 232 Th system at 340 MeV

International Nuclear Information System (INIS)

Prete, G.; Rizzi, V.; Fioretto, E.; Cinausero, M.; Shetty, D.V.; Pesente, S.; Brondi, A.; La Rana, G.; Moro, R.; Vardaci, E.; Boiano, A.; Ordine, A.; Gelli, N.; Lucarelli, F.; Bortignon, P.F.; Saxena, A.; Nayak, B.K.; Biswas, D.C.; Choudhury, R.K.; Kapoor, R.S.

2001-01-01

Full text: Fission induced by nucleons transfer has been investigated in the reaction 28 Si + 232 Th at 340 MeV. Looking at the projectile-like-fragments (PLF), the fission yield increases as the transfer increases, but a decreases is observed for transfers with DZ . Light charged particles in coincidence with PLF and Fission have been detected with large solid angle and show an increasing multiplicity as the Z of PLF is reduced and a constant value when fission is requested. The present results indicate inhibition of transfer induced fission reaction for higher Z transfer and increasing probability for decay through charged particle evaporation. Fission is the dominant decay process in heavy reactions involving fissile systems but the dynamical evolution of the composite system is largely governed by the formation and decay mechanisms. Important insight into the formation and the survival probability of the heavy composite nuclei formed in heavy ion collisions can be gained by simultaneously investigate the fission process and light particle emission over a continuous range of excitation energy, angular momentum and fissility. This can be achieved by studying fission induced by transfer of nucleons between the interacting projectile and the target nucleus. In the present work, we have carried out measurements on multinucleon transfer induced fission reactions in 28 Si + 232 Th system at Elab = 340 MeV. The experiment has been performed at the Laboratori Nazionale di Legnaro (LNL) using the 8pLP detector in its final configuration with 257 DE-E telescopes. The backward detectors were used to measure both light charged particles and fission fragments. The projectile-like fragments were detected using separate DE-E telescopes around the grazing angle. Two neutron detectors were placed at a distance of 115.5 cm from the target to measure neutrons emitted in coincidence with fission fragments. Here we present the results of the data analysis of transfer induced fission

Altered Mitochondrial Dynamics and TBI Pathophysiology

Directory of Open Access Journals (Sweden)

Tara Diane Fischer

2016-03-01

Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

Influence of the cosmic-ray induced fission tracks on the fission track of extraterrestric minerals via the 238U spontaneous fission

International Nuclear Information System (INIS)

Damm, G.; Thiel, K.

1977-01-01

The age determined by counting fission tracks of lunar and meteorite materials is obviously falsified by additional fission track parts not to be accounted for by the spontaneous fission of uranium 238. For this p and n induced fissions of U, Th and other hreavy elements through the cosmic radiation come into consideration. In order to determine the possible part of such interference factors, a simulation experiment at the proton synchrocycloton (CERN, Geneva) has been carried out and independently of this, the production rates for the p and n induced U, Th, Bi, Pb and Au in the surface-near regolith layers of the moon were calculated. It could be seen that the irradiation age as well as the spacial distribution of the heavy metals in the samples to be dated must be considered. (RB) [de

The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe

Energy Technology Data Exchange (ETDEWEB)

Wang, Yiwei; Gulis, Galina; Buckner, Scott; Johnson, P. Connor; Sullivan, Daniel [Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487 (United States); Busenlehner, Laura [Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487 (United States); Marcus, Stevan, E-mail: smarcus@bama.ua.edu [Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487 (United States)

2010-08-20

Research highlights: {yields} Rotenone induces generation of ROS and mitochondrial fragmentation in fission yeast. {yields} The MAPK Pmk1 and PKA are required for rotenone resistance in fission yeast. {yields} Pmk1 and PKA are required for ROS clearance in rotenone treated fission yeast cells. {yields} PKA plays a role in ROS clearance under normal growth conditions in fission yeast. -- Abstract: Rotenone is a widely used pesticide that induces Parkinson's disease-like symptoms in rats and death of dopaminergic neurons in culture. Although rotenone is a potent inhibitor of complex I of the mitochondrial electron transport chain, it can induce death of dopaminergic neurons independently of complex I inhibition. Here we describe effects of rotenone in the fission yeast, Schizosaccharomyces pombe, which lacks complex I and carries out rotenone-insensitive cellular respiration. We show that rotenone induces generation of reactive oxygen species (ROS) as well as fragmentation of mitochondrial networks in treated S. pombe cells. While rotenone is only modestly inhibitory to growth of wild type S. pombe cells, it is strongly inhibitory to growth of mutants lacking the ERK-type MAP kinase, Pmk1, or protein kinase A (PKA). In contrast, cells lacking the p38 MAP kinase, Spc1, exhibit modest resistance to rotenone. Consistent with these findings, we provide evidence that Pmk1 and PKA, but not Spc1, are required for clearance of ROS in rotenone treated S. pombe cells. Our results demonstrate the usefulness of S. pombe for elucidating complex I-independent molecular targets of rotenone as well as mechanisms conferring resistance to the toxin.

The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe

International Nuclear Information System (INIS)

Wang, Yiwei; Gulis, Galina; Buckner, Scott; Johnson, P. Connor; Sullivan, Daniel; Busenlehner, Laura; Marcus, Stevan

2010-01-01

Research highlights: → Rotenone induces generation of ROS and mitochondrial fragmentation in fission yeast. → The MAPK Pmk1 and PKA are required for rotenone resistance in fission yeast. → Pmk1 and PKA are required for ROS clearance in rotenone treated fission yeast cells. → PKA plays a role in ROS clearance under normal growth conditions in fission yeast. -- Abstract: Rotenone is a widely used pesticide that induces Parkinson's disease-like symptoms in rats and death of dopaminergic neurons in culture. Although rotenone is a potent inhibitor of complex I of the mitochondrial electron transport chain, it can induce death of dopaminergic neurons independently of complex I inhibition. Here we describe effects of rotenone in the fission yeast, Schizosaccharomyces pombe, which lacks complex I and carries out rotenone-insensitive cellular respiration. We show that rotenone induces generation of reactive oxygen species (ROS) as well as fragmentation of mitochondrial networks in treated S. pombe cells. While rotenone is only modestly inhibitory to growth of wild type S. pombe cells, it is strongly inhibitory to growth of mutants lacking the ERK-type MAP kinase, Pmk1, or protein kinase A (PKA). In contrast, cells lacking the p38 MAP kinase, Spc1, exhibit modest resistance to rotenone. Consistent with these findings, we provide evidence that Pmk1 and PKA, but not Spc1, are required for clearance of ROS in rotenone treated S. pombe cells. Our results demonstrate the usefulness of S. pombe for elucidating complex I-independent molecular targets of rotenone as well as mechanisms conferring resistance to the toxin.

238U subthreshold neutron induced fission cross section

International Nuclear Information System (INIS)

Difilippo, F.C.; Perez, R.B.; De Saussure, G.; Olsen, D.K.; Ingle, R.W.

1976-01-01

High resolution measurements of the 238 U neutron induced fission cross section are reported for neutron energies between 600 eV and 2 MeV. The average subthreshold fission cross section between 10 and 100 keV was found to be 44 +- 6 μb

Mass distributions in nucleon-induced fission at intermediate energies

CERN Document Server

Duijvestijn, M C; Hambsch, F J

2001-01-01

Temperature-dependent fission barriers and fission-fragment mass distributions are calculated in the framework of the multimodal random neck-rupture model (MM-RNRM). It is shown how the distinction between the different fission modes disappears at higher excitation energies, due to the melting of shell effects. The fission-fragment mass yield calculations are coupled to the nuclear reaction code ALICE-91, which takes into account the competition between the other reaction channels and fission. With the combination of the temperature-dependent MM-RNRM and ALICE-91 nucleon-induced fission is investigated at energies between 10 and 200 MeV for nuclei varying from Au to Am. (72 refs).

Troxerutin attenuates diet-induced oxidative stress, impairment of mitochondrial biogenesis and respiratory chain complexes in mice heart.

Science.gov (United States)

Rajagopalan, Geetha; Chandrasekaran, Sathiya Priya; Carani Venkatraman, Anuradha

2017-01-01

Mitochondrial abnormality is thought to play a key role in cardiac disease originating from the metabolic syndrome (MS). We evaluated the effect of troxerutin (TX), a semi-synthetic derivative of the natural bioflavanoid rutin, on the respiratory chain complex activity, oxidative stress, mitochondrial biogenesis and dynamics in heart of high fat, high fructose diet (HFFD) -induced mouse model of MS. Adult male Mus musculus mice of body weight 25-30 g were fed either control diet or HFFD for 60 days. Mice from each dietary regimen were divided into two groups on the 16th day and were treated or untreated with TX (150 mg/kg body weight [bw], per oral) for the next 45 days. At the end of experimental period, respiratory chain complex activity, uncoupling proteins (UCP)-2 and -3, mtDNA content, mitochondrial biogenesis and dynamics, oxidative stress markers and reactive oxygen species (ROS) generation were analyzed. Reduced mtDNA abundance with alterations in the expression of genes related to mitochondrial biogenesis and fission and fusion processes were observed in HFFD-fed mice. Disorganized and smaller mitochondria, reduction in complexes I, III and IV activities (by about 55%) and protein levels of UCP-2 (52%) and UCP-3 (46%) were noted in these mice. TX administration suppressed oxidative stress, improved the oxidative capacity and biogenesis and restored fission/fusion imbalance in the cardiac mitochondria of HFFD-fed mice. TX protects the myocardium by modulating the putative molecules of mitochondrial biogenesis and dynamics and by its anti-oxidant function in a mouse model of MS. © 2016 John Wiley & Sons Australia, Ltd.

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN

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Annalisa Canta

2015-06-01

Full Text Available The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN. This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy.

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Science.gov (United States)

Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

2015-01-01

The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658

High-energy Neutron-induced Fission Cross Sections of Natural Lead and Bismuth-209

CERN Document Server

Tarrio, D; Carrapico, C; Eleftheriadis, C; Leeb, H; Calvino, F; Herrera-Martinez, A; Savvidis, I; Vlachoudis, V; Haas, B; Koehler, P; Vannini, G; Oshima, M; Le Naour, C; Gramegna, F; Wiescher, M; Pigni, M T; Audouin, L; Mengoni, A; Quesada, J; Becvar, F; Plag, R; Cennini, P; Mosconi, M; Rauscher, T; Couture, A; Capote, R; Sarchiapone, L; Vlastou, R; Domingo-Pardo, C; Dillmann, I; Pavlopoulos, P; Karamanis, D; Krticka, M; Jericha, E; Ferrari, A; Martinez, T; Trubert, D; Oberhummer, H; Karadimos, D; Plompen, A; Isaev, S; Terlizzi, R; Cortes, G; Cox, J; Cano-Ott, D; Pretel, C; Colonna, N; Berthoumieux, E; Vaz, P; Heil, M; Lopes, I; Lampoudis, C; Walter, S; Calviani, M; Gonzalez-Romero, E; Embid-Segura, M; Stephan, C; Igashira, M; Papachristodoulou, C; Aerts, G; Tavora, L; Berthier, B; Rudolf, G; Andrzejewski, J; Villamarin, D; Ferreira-Marques, R; Tain, J L; O'Brien, S; Reifarth, R; Kadi, Y; Neves, F; Poch, A; Kerveno, M; Rubbia, C; Lazano, M; Dahlfors, M; Wisshak, K; Salgado, J; Dridi, W; Ventura, A; Andriamonje, S; Assimakopoulos, P; Santos, C; Voss, F; Ferrant, L; Patronis, N; Chiaveri, E; Guerrero, C; Perrot, L; Vicente, M C; Lindote, A; Praena, J; Baumann, P; Kappeler, F; Rullhusen, P; Furman, W; David, S; Marrone, S; Tassan-Got, L; Gunsig, F; Alvarez-Velarde, F; Massimi, C; Mastinu, P; Pancin, J; Papadopoulos, C; Tagliente, G; Haight, R; Chepel, V; Kossionides, E; Badurek, G; Marganiec, J; Lukic, S; Pavlik, A; Goncalves, I; Duran, I; Alvarez, H; Abbondanno, U; Fujii, K; Milazzo, P M; Moreau, C

2011-01-01

The CERN Neutron Time-Of-Flight (n\\_TOF) facility is well suited to measure small neutron-induced fission cross sections, as those of subactinides. The cross section ratios of (nat)Pb and (209)Bi relative to (235)U and (238)U were measured using PPAC detectors. The fragment coincidence method allows to unambiguously identify the fission events. The present experiment provides the first results for neutron-induced fission up to 1 GeV for (nat)Pb and (209)Bi. A good agreement with previous experimental data below 200 MeV is shown. The comparison with proton-induced fission indicates that the limiting regime where neutron-induced and proton-induced fission reach equal cross section is close to 1 GeV.

Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts

DEFF Research Database (Denmark)

Guillery, O.; Malka, F.; Frachon, P.

2008-01-01

induced partial but significant mitochondrial fragmentation, whereas dissipation of mitochondrial membrane potential (D Psi m) provoked complete fragmentation, and glycolysis inhibition had no effect. Oxidative phosphorylation defective fibroblasts had essentially normal filamentous mitochondria under...... basal conditions, although when challenged some of them presented with mild alteration of fission or fusion efficacy. Severely defective cells disclosed complete mitochondrial fragmentation under glycolysis inhibition. In conclusion, mitochondrial morphology is modulated by D Psi m but loosely linked...... to mitochondrial oxidative phosphorylation. Its alteration by glycolysis, inhibition points to a severe oxidative phosphorylation defect. (C) 2008 Elsevier B.V. All rights reserved Udgivelsesdato: 2008/4...

Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

International Nuclear Information System (INIS)

Cherubini, Marta; Ginés, Silvia

2017-01-01

Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

Fission induced swelling of U–Mo/Al dispersion fuel

Energy Technology Data Exchange (ETDEWEB)

Kim, Yeon Soo, E-mail: yskim@anl.gov [Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Jeong, G.Y. [Ulsan National Institute of Science and Technology, 50 UNIST-gil, Eonyang-eup, Uljoo-gun, Ulsan 689-798 (Korea, Republic of); Park, J.M. [Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Robinson, A.B. [Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-6188 (United States)

2015-10-15

Fission-induced swelling of U–Mo/Al dispersion fuel meat was measured using microscopy images obtained from post-irradiation examination. The data of reduced-size plate-type test samples and rod-type test samples were employed for this work. A model to predict the meat swelling of U–Mo/Al dispersion fuel was developed. This model is composed of several submodels including a model for interaction layer (IL) growth between U–Mo and Al matrix, a model for IL thickness to IL volume conversion, a correlation for the fission-induced swelling of U–Mo alloy particles, a correlation for the fission-induced swelling of IL, and models of U–Mo and Al consumption by IL growth. The model was validated using full-size plate data that were not included in the model development.

Independent fission yields of Rb and Cs from thermal-neutron-induced fission of 239Pu

International Nuclear Information System (INIS)

Balestrini, S.J.; Forman, L.

1975-01-01

The relative independent fission yields of Rb and Cs from thermal-neutron-induced fission of 239 Pu have been measured on line using a mass spectrograph and thermalized neutrons from a burst reactor. Independent yields were derived by normalizing the measurements to products of chain yields and fractional independent yields, estimating the latter from measured cumulative yields of Kr and Xe. Comparing the independent yields with those from 238 U fission, the 239 Pu results show shifts in isotopic yield distribution toward lower mass for both Rb and Cs and also toward the production of more Cs and less Rb when 239 Pu is fissioned

Systematics of neutron-induced fission yields

International Nuclear Information System (INIS)

Blachot, J.; Brissot, R.

1983-10-01

The main characteristics of the mass and charge distributions for thermal neutron induced fission of actinides are reviewed. We show that these distributions can be reasonably reproduced with only 24 data as input. We use a representation where the element yields together with the most probable mass Ap(Z) play the dominant role. The ability of this model to calculate mass yields for the fission of not yet measured actinides is also shown. The influence of the excitation energy of the fissile system on charge and mass distribution is also discussed

HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation

International Nuclear Information System (INIS)

Kim, Hak-June; Nagano, Yoshito; Choi, Su Jin; Park, Song Yi; Kim, Hongtae; Yao, Tso-Pang; Lee, Joo-Yong

2015-01-01

Mitochondria undergo fusion and fission in response to various metabolic stresses. Growing evidences have suggested that the morphological change of mitochondria by fusion and fission plays a critical role in protecting mitochondria from metabolic stresses. Here, we showed that hypoxia treatment could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6 deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus protecting mitochondrial connectivity from hypoxic stress. - Highlights: • Hypoxic stress induces the interaction between HDAC6 and MFN2. • Hypoxic stress activates MARCH5 in HDAC6 deficient cells to degrade MFN2. • HDAC6 is required to maintain mitochondrial connectivity under hypoxia. • MARCH5 is increased and promotes the degradation of MFN2 in HDAC6 KO ALS mice

HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation

Energy Technology Data Exchange (ETDEWEB)

Kim, Hak-June [Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Nagano, Yoshito [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, 734-8551 (Japan); Choi, Su Jin; Park, Song Yi [Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Kim, Hongtae [Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon, 440-746 (Korea, Republic of); Yao, Tso-Pang, E-mail: tsopang.yao@duke.edu [Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710 (United States); Lee, Joo-Yong, E-mail: leejooyong@cnu.ac.kr [Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of)

2015-09-04

Mitochondria undergo fusion and fission in response to various metabolic stresses. Growing evidences have suggested that the morphological change of mitochondria by fusion and fission plays a critical role in protecting mitochondria from metabolic stresses. Here, we showed that hypoxia treatment could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6 deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus protecting mitochondrial connectivity from hypoxic stress. - Highlights: • Hypoxic stress induces the interaction between HDAC6 and MFN2. • Hypoxic stress activates MARCH5 in HDAC6 deficient cells to degrade MFN2. • HDAC6 is required to maintain mitochondrial connectivity under hypoxia. • MARCH5 is increased and promotes the degradation of MFN2 in HDAC6 KO ALS mice.

Suppression of Cpn10 increases mitochondrial fission and dysfunction in neuroblastoma cells.

Directory of Open Access Journals (Sweden)

So Jung Park

Full Text Available To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10 interacts with heat shock protein 60 (HSP60 and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.

Intact initiation of autophagy and mitochondrial fission by acute exercise in skeletal muscle of patientswith type 2 diabetes

DEFF Research Database (Denmark)

Kruse Sørensen, Rikke; Pedersen, Andreas James Thestrup; Kristensen, Jonas Møller

2017-01-01

AIMS: Type 2 diabetes (T2D) is characterized by insulin resistance, mitochondrial dysregulation, and, in some studies, exercise resistance in skeletal muscle. Regulation of autophagy and mitochondrial dynamics during exercise and recovery is important for skeletal muscle homeostasis......, and these responses may be altered in T2D. MATERIALS AND METHODS: We examined the effect of acute exercise on markers of autophagy and mitochondrial fusion and fission in skeletal muscle biopsies from patients with T2D (n=13) and weight-matched controls (n=14) before, immediately after and 3h after an acute bout...... of exercise. RESULTS: While mRNA levels of most markers of autophagy ( PIK3C, MAP1LC3B, SQSTM1, BNIP3, BNIP3L ) and mitochondrial dynamics ( OPA1, FIS1 ) remained unchanged, some either increased during and after exercise (GABARAPL1 ), decreased in the recovery period ( BECN1, ATG7, DNM1L ), or both ( MFN2...

Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities.

Science.gov (United States)

Di Pietro, Valentina; Lazzarino, Giacomo; Amorini, Angela Maria; Signoretti, Stefano; Hill, Lisa J; Porto, Edoardo; Tavazzi, Barbara; Lazzarino, Giuseppe; Belli, Antonio

2017-08-23

Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.

Photon and proton induced fission on heavy nuclei at intermediate energies

Directory of Open Access Journals (Sweden)

Andrade-II E.

2014-04-01

Full Text Available We present an analysis of fission induced by intermediate energy protons or photons on actinides. The 660 MeV proton induced reactions are on 241Am, 238U, and 237Np targets and the Bremmstrahlung-photons with end-point energies at 50 MeV and 3500 MeV are on 232Th and 238U targets. The study was performed by means of the Monte Carlo simulation code CRISP. A multimodal fission extension was added to the code within an approach which accounts for the contribution of symmetric and asymmetric fission. This procedure allowed the investigation of fission cross sections, fissility, number of evaporated nucleons and fission-fragment charge distributions. The comparison with experimental data show a good agreement between calculations and experiments.

Dynamical chaos and induced nuclear fission

Energy Technology Data Exchange (ETDEWEB)

Bolotin, Yu L; Krivoshej, I V

1985-01-01

It is shown that the exponential instability of trajectories, which arises at negative curvature of the potential energy surface, leads to diffusion of the image point through the barrier and determines real time delays in induced nuclear fission.

Dynamin-Related Protein 1 Inhibitors Protect against Ischemic Toxicity through Attenuating Mitochondrial Ca2+ Uptake from Endoplasmic Reticulum Store in PC12 Cells

Directory of Open Access Journals (Sweden)

Ye Tian

2014-02-01

Full Text Available Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction related diseases. Here, we investigated the effects of mitochondrial division inhibitor A (mdivi A and mdivi B, two small molecule inhibitors of mitochondrial fission protein dunamin-related protein 1 (Drp-1, in neuronal injury induced by oxygen-glucose deprivation (OGD in PC12 cells. We found that mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating apoptotic cell death. These two inhibitors also preserved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS generation and cytochrome c release, as well as prevented loss of mitochondrial membrane potential (MMP. Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca2+ uptake, but had no effect on cytoplasmic Ca2+ after OGD injury. The results of calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors attenuated endoplasmic reticulum (ER Ca2+ release and prevented ER morphological changes induced by OGD. These results demonstrate that Drp-1 inhibitors protect against ischemic neuronal injury through inhibiting mitochondrial Ca2+ uptake from the ER store and attenuating mitochondrial dysfunction.

Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage.

Science.gov (United States)

Bachmann, Rosilla F; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K

2009-07-01

Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially mediated neurotoxicity. We found that long-term treatment with lithium and valproate (VPA) enhanced cell respiration rate. Furthermore, chronic treatment with lithium or VPA enhanced mitochondrial function as determined by mitochondrial membrane potential, and mitochondrial oxidation in SH-SY5Y cells. In-vivo studies showed that long-term treatment with lithium or VPA protected against methamphetamine (Meth)-induced toxicity at the mitochondrial level. Furthermore, these agents prevented the Meth-induced reduction of mitochondrial cytochrome c, the mitochondrial anti-apoptotic Bcl-2/Bax ratio, and mitochondrial cytochrome oxidase (COX) activity. Oligoarray analysis demonstrated that the gene expression of several proteins related to the apoptotic pathway and mitochondrial functions were altered by Meth, and these changes were attenuated by treatment with lithium or VPA. One of the genes, Bcl-2, is a common target for lithium and VPA. Knock-down of Bcl-2 with specific Bcl-2 siRNA reduced the lithium- and VPA-induced increases in mitochondrial oxidation. These findings illustrate that lithium and VPA enhance mitochondrial function and protect against mitochondrially mediated toxicity. These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia.

Mitochondrial Dynamics in Cardiovascular Health and Disease

OpenAIRE

Ong, Sang-Bing; Hall, Andrew R.; Hausenloy, Derek J.

2013-01-01

Significance: Mitochondria are dynamic organelles capable of changing their shape and distribution by undergoing either fission or fusion. Changes in mitochondrial dynamics, which is under the control of specific mitochondrial fission and fusion proteins, have been implicated in cell division, embryonic development, apoptosis, autophagy, and metabolism. Although the machinery for modulating mitochondrial dynamics is present in the cardiovascular system, its function there has only recently be...

ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

International Nuclear Information System (INIS)

Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

2015-01-01

Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy

The Growth of Sea cucumber Stichopus herrmanni After Transverse Induced Fission in Two and Three Fission Plane

Directory of Open Access Journals (Sweden)

Retno Hartati

2016-06-01

Full Text Available Transverse induced fission proven could be done in Teripang Tril, Stichopus herrmanni. This present works aimed to analyze wound recovery, regeneration period and growth of Teripang Trill  after asexual reproduction by fission using two and three fission plane. Observations were made every day until the sea cucumber body separated into two or more (depending on treatment and reared for 16 weeks.  The results showed that there are differences in wound recovery, regeneration period and growth of S. herrmanni depend on their different fission plane. The wound recovery and regeneration period (days of anterior, middle and posterior individu S. herrmanni resulted from two and three fission plane were varied but the two fission plane the anterior individu recover for longer period than posterior part and  the wound recover process in both end for thee fission plane was same. Average growth of anterior and posterior fragment were longer for two fission plane than three fission plane.  The middle fragment (M1 and M2 both fission plane was able to grow but very low.  It showed that three fission plane gave very slow growth in every fragment of the body. Keywords: growth, post-fission, fission plane, Stichopus herrmanni

Photon and proton induced fission on heavy nuclei at intermediate energies

Energy Technology Data Exchange (ETDEWEB)

Andrade-II, E.; Karapetyan, G.S.; Deppman, A.; Guimaraes, V. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica; Balabekyan, A.R. [Yerevan State University, Alex Manoogian 1, Yerevan (Armenia); Demekhina, N.A. [Yerevan Physics Institute, Alikhanyan Brothers 2, Yerevan (Armenia); Joint Institute for Nuclear Research (JINR), Flerov Laboratory of Nuclear Reactions (LNR), Moscow (Russian Federation)

2014-07-01

We present an analysis of fission induced by intermediate energy protons or photons on actinides. The 660 MeV proton induced reactions are on {sup 241}Am, {sup 238}U, and {sup 237}Np targets and the Bremsstrahlung-photons with end-point energies at 50 MeV and 3500 MeV are on {sup 232}Th and {sup 238}U targets. The study was performed by means of the Monte Carlo simulation code CRISP. A multimodal fission extension was added to the code within an approach which accounts for the contribution of symmetric and asymmetric fission. This procedure allowed the investigation of fission cross sections, fissility, number of evaporated nucleons and fission-fragment charge distributions. The comparison with experimental data show a good agreement between calculations and experiments. (author)

Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression.

Science.gov (United States)

Collins, Steven J; Tumpach, Carolin; Groveman, Bradley R; Drew, Simon C; Haigh, Cathryn L

2018-03-24

Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life.

Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

Science.gov (United States)

Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

2018-05-02

Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

Determination of the neutron-induced fission cross section of 242Pu

International Nuclear Information System (INIS)

Koegler, Toni Joerg

2016-01-01

Neutron induced fission cross sections of actinides like the Pu-isotopes are of relevance for the development of nuclear transmutation technologies. For 242 Pu, current uncertainties are of around 21%. Sensitivity studies show that the total uncertainty has to be reduced to below 5% to allow for reliable neutron physics simulations. This challenging task was performed at the neutron time-of-flight facility of the new German National Center for High Power Radiation Sources at HZDR, Dresden. Within the TRAKULA project, thin, large and homogeneous deposits of 235 U and 242 Pu have been produced successfully. Using two consecutively placed fission chambers allowed the determination of the neutron induced fission cross section of 242 Pu relative to 235 U. The areal density of the Plutonium targets was calculated using the measured spontaneous fission rate. Experimental results of the fast neutron induced fission of 242 Pu acquired at nELBE will be presented and compared to recent experiments and evaluated data. Corrections addressing the neutron scattering are discussed by using results of different neutron transport simulations (Geant 4, MCNP 6 and FLUKA).

Dose-effect relationship of apoptosis induced by fission-neutron in murine thymocytes

International Nuclear Information System (INIS)

Yuan Bin; Li Liang; Xue Wencheng; Sun Jianmin; Wang Baoqin

2000-01-01

Objective: To investigate the effectiveness of high LET fission-neutron to induce apoptosis in murine thymocytes and to compare it with that of low LET 60 Co γ-ray. Methods: Apoptosis induction was studied qualitatively by light and transmission electron microscopy and DNA gel electrophoresis,also quantitatively by flow cytometry(FCM) and diphenylamine (DPA)methods. Results: DNA ladders of murine thymocytes were detectable, the typical apoptosis of thymocytes could be observed morphologically by means of light and electron microscopy at 6 h after fission-neutron irradiation with doses ranging from 0.5 to 5.0 Gy, meanwhile the percentages of apoptosis increased with increasing doses. After exposure to γ-rays with doses ranging from 1.0 to 30 Gy, the experimental results were similar to those from neutron radiation. The incidence of apoptosis peaked at about 20 Gy, the percentages did not increase further when doses increased. Conclusion: Apoptosis of murine thymocytes can be induced when mice are exposed to either fission-neutron (0.5-5.0 Gy) or to γ-ray (1-30 Gy). Although the relationship between apoptosis and radiation doses is similar, the percentage of apoptosis induced by neutron irradiation is higher than that induced by γ-irradiation. The RBE values of fission-neutron for inducing apoptosis murine thymocytes are 2.09 (by FCM method) and 2.37 (by DPA method), respectively. These results also suggest that fission-neutron-induced murine immune tissue is more severe than that induced by γ-rays at several hours post-irradiation and this might be the basis for heavy damage to immune tissues induced by fission-neutron-irradiation in later period

Dynamin-related protein inhibitor downregulates reactive oxygen species levels to indirectly suppress high glucose-induced hyperproliferation of vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Maimaitijiang, Alimujiang; Zhuang, Xinyu; Jiang, Xiaofei; Li, Yong, E-mail: 11211220031@fudan.edu.cn

2016-03-18

Hyperproliferation of vascular smooth muscle cells is a pathogenic mechanism common in diabetic vascular complications and is a putatively important therapeutic target. This study investigated multiple levels of biology, including cellular and organellar changes, as well as perturbations in protein synthesis and morphology. Quantitative and qualitative analysis was utilized to assess the effect of mitochondrial dynamic changes and reactive oxygen species(ROS) levels on high-glucose-induced hyperproliferation of vascular smooth muscle cells. The data demonstrated that the mitochondrial fission inhibitor Mdivi-1 and downregulation of ROS levels both effectively inhibited the high-glucose-induced hyperproliferation of vascular smooth muscle cells. Downregulation of ROS levels played a more direct role and ROS levels were also regulated by mitochondrial dynamics. Increased ROS levels induced excessive mitochondrial fission through dynamin-related protein (Drp 1), while Mdivi-1 suppressed the sensitivity of Drp1 to ROS levels, thus inhibiting excessive mitochondrial fission under high-glucose conditions. This study is the first to propose that mitochondrial dynamic changes and ROS levels interact with each other and regulate high-glucose-induced hyperproliferation of vascular smooth muscle cells. This finding provides novel ideas in understanding the pathogenesis of diabetic vascular remodeling and intervention. - Highlights: • Mdivi-1 inhibits VSMC proliferation by lowering ROS level in high-glucose condition. • ROS may be able to induce mitochondrial fission through Drp1 regulation. • Mdivi-1 can suppress the sensitivity of Drp1 to ROS.

MoDnm1 Dynamin Mediating Peroxisomal and Mitochondrial Fission in Complex with MoFis1 and MoMdv1 Is Important for Development of Functional Appressorium in Magnaporthe oryzae.

Directory of Open Access Journals (Sweden)

Kaili Zhong

2016-08-01

Full Text Available Dynamins are large superfamily GTPase proteins that are involved in various cellular processes including budding of transport vesicles, division of organelles, cytokinesis, and pathogen resistance. Here, we characterized several dynamin-related proteins from the rice blast fungus Magnaporthe oryzae and found that MoDnm1 is required for normal functions, including vegetative growth, conidiogenesis, and full pathogenicity. In addition, we found that MoDnm1 co-localizes with peroxisomes and mitochondria, which is consistent with the conserved role of dynamin proteins. Importantly, MoDnm1-dependent peroxisomal and mitochondrial fission involves functions of mitochondrial fission protein MoFis1 and WD-40 repeat protein MoMdv1. These two proteins display similar cellular functions and subcellular localizations as MoDnm1, and are also required for full pathogenicity. Further studies showed that MoDnm1, MoFis1 and MoMdv1 are in complex to regulate not only peroxisomal and mitochondrial fission, pexophagy and mitophagy progression, but also appressorium function and host penetration. In summary, our studies provide new insights into how MoDnm1 interacts with its partner proteins to mediate peroxisomal and mitochondrial functions and how such regulatory events may link to differentiation and pathogenicity in the rice blast fungus.

Above-threshold structure in {sup 244}Cm neutron-induced fission cross section

Energy Technology Data Exchange (ETDEWEB)

Maslov, V.M. [Radiation Physics and Chemistry Problems Inst., Minsk-Sosny (Belarus)

1997-03-01

The quasi-resonance structure appearing above the fission threshold in neutron-induced fission cross section of {sup 244}Cm(n,f) is interpreted. It is shown to be due to excitation of few-quasiparticle states in fissioning {sup 245}Cm and residual {sup 244}Cm nuclides. The estimate of quasiparticle excitation thresholds in fissioning nuclide {sup 245}Cm is consistent with pairing gap and fission barrier parameters. (author)

High-precision spectrometer for studies of ion-induced and spontaneous fission dynamics

International Nuclear Information System (INIS)

Batenkov, O.; Elmgren, K.; Majorov, M.; Blomgren, J.; Conde, H.; Hultqvist, S.; Olsson, N.; Rahm, J.; Ramstroem, E.; Smirnov, S.; Veshikov, A.

1997-01-01

A spectrometer has been designed and built to investigate the dynamics of spontaneous and ion-induced fission processes. It consists of 8 neutron detectors surrounding a low mass scattering chamber containing the fissionable targets and two fission fragment telescopes. The spectrometer measures neutron spectra, and energy and angular correlations of neutrons, as well as kinetic energy, mass, and relative angle of fission fragments. A 252 Cf fission reference source is used for calibration. (orig.)

Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress

Directory of Open Access Journals (Sweden)

Min Guo

2018-03-01

Full Text Available Background: Neuroprotective effects of ketogenic diets (KD have been reported in stroke models, and nucleotide-binding domain (NOD-like receptor protein 3 (NLRP3 inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms.Methods: In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB followed by oxygen–glucose deprivation/reoxygenation (OGD/R. NLRP3 inflammasome activation and related regulatory mechanisms were evaluated.Results: Mice fed with KD had increased tolerance to MCAO/R. KD inhibited endoplasmic reticulum (ER stress and suppressed TXNIP/NLRP3 inflammasome activation in the brain. The in vitro study showed BHB (10 mM prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1 to inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species (ROS generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and suppressed ER stress-induced NLRP3 inflammasome activation.Conclusions: KD may suppress ER stress and protect mitochondrial integrity by suppressing the mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation, thus exerting neuroprotective effects. Our findings provide evidence for the potential application of KD in the prevention of ischemic stroke.

Event-by-Event Simulation of Induced Fission

Energy Technology Data Exchange (ETDEWEB)

Vogt, R; Randrup, J

2007-12-13

We are developing a novel code that treats induced fission by statistical (or Monte-Carlo) simulation of individual decay chains. After its initial excitation, the fissionable compound nucleus may either deexcite by evaporation or undergo binary fission into a large number of fission channels each with different energetics involving both energy dissipation and deformed scission prefragments. After separation and Coulomb acceleration, each fission fragment undergoes a succession of individual (neutron) evaporations, leading to two bound but still excited fission products (that may further decay electromagnetically and, ultimately, weakly), as well as typically several neutrons. (The inclusion of other possible ejectiles is planned.) This kind of approach makes it possible to study more detailed observables than could be addressed with previous treatments which have tended to focus on average quantities. In particular, any type of correlation observable can readily be extracted from a generated set of events. With a view towards making the code practically useful in a variety of applications, emphasis is being put on making it numerically efficient so that large event samples can be generated quickly. In its present form, the code can generate one million full events in about 12 seconds on a MacBook laptop computer. The development of this qualitatively new tool is still at an early stage and quantitative reproduction of existing data should not be expected until a number of detailed refinement have been implemented.

Event-by-Event Simulation of Induced Fission

Science.gov (United States)

Vogt, Ramona; Randrup, Jørgen

2008-04-01

We are developing a novel code that treats induced fission by statistical (or Monte-Carlo) simulation of individual decay chains. After its initial excitation, the fissionable compound nucleus may either de-excite by evaporation or undergo binary fission into a large number of fission channels each with different energetics involving both energy dissipation and deformed scission pre-fragments. After separation and Coulomb acceleration, each fission fragment undergoes a succession of individual (neutron) evaporations, leading to two bound but still excited fission products (that may further decay electromagnetically and, ultimately, weakly), as well as typically several neutrons. (The inclusion of other possible ejectiles is planned.) This kind of approach makes it possible to study more detailed observables than could be addressed with previous treatments which have tended to focus on average quantities. In particular, any type of correlation observable can readily be extracted from a generated set of events. With a view towards making the code practically useful in a variety of applications, emphasis is being put on making it numerically efficient so that large event samples can be generated quickly. In its present form, the code can generate one million full events in about 12 seconds on a MacBook laptop computer. The development of this qualitatively new tool is still at an early stage and quantitative reproduction of existing data should not be expected until a number of detailed refinement have been implemented.

Event-by-Event Simulation of Induced Fission

International Nuclear Information System (INIS)

Vogt, Ramona; Randrup, Joergen

2008-01-01

We are developing a novel code that treats induced fission by statistical (or Monte-Carlo) simulation of individual decay chains. After its initial excitation, the fissionable compound nucleus may either de-excite by evaporation or undergo binary fission into a large number of fission channels each with different energetics involving both energy dissipation and deformed scission pre-fragments. After separation and Coulomb acceleration, each fission fragment undergoes a succession of individual (neutron) evaporations, leading to two bound but still excited fission products (that may further decay electromagnetically and, ultimately, weakly), as well as typically several neutrons. (The inclusion of other possible ejectiles is planned.) This kind of approach makes it possible to study more detailed observables than could be addressed with previous treatments which have tended to focus on average quantities. In particular, any type of correlation observable can readily be extracted from a generated set of events. With a view towards making the code practically useful in a variety of applications, emphasis is being put on making it numerically efficient so that large event samples can be generated quickly. In its present form, the code can generate one million full events in about 12 seconds on a MacBook laptop computer. The development of this qualitatively new tool is still at an early stage and quantitative reproduction of existing data should not be expected until a number of detailed refinement have been implemented

Event-by-Event Simulation of Induced Fission

International Nuclear Information System (INIS)

Vogt, R; Randrup, J

2007-01-01

We are developing a novel code that treats induced fission by statistical (or Monte-Carlo) simulation of individual decay chains. After its initial excitation, the fissionable compound nucleus may either deexcite by evaporation or undergo binary fission into a large number of fission channels each with different energetics involving both energy dissipation and deformed scission prefragments. After separation and Coulomb acceleration, each fission fragment undergoes a succession of individual (neutron) evaporations, leading to two bound but still excited fission products (that may further decay electromagnetically and, ultimately, weakly), as well as typically several neutrons. (The inclusion of other possible ejectiles is planned.) This kind of approach makes it possible to study more detailed observables than could be addressed with previous treatments which have tended to focus on average quantities. In particular, any type of correlation observable can readily be extracted from a generated set of events. With a view towards making the code practically useful in a variety of applications, emphasis is being put on making it numerically efficient so that large event samples can be generated quickly. In its present form, the code can generate one million full events in about 12 seconds on a MacBook laptop computer. The development of this qualitatively new tool is still at an early stage and quantitative reproduction of existing data should not be expected until a number of detailed refinement have been implemented

Fission induced swelling and creep of U–Mo alloy fuel

Energy Technology Data Exchange (ETDEWEB)

Kim, Yeon Soo, E-mail: yskim@anl.gov [Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Hofman, G.L. [Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Cheon, J.S. [Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong, Daejeon 305-353 (Korea, Republic of); Robinson, A.B.; Wachs, D.M. [Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415 (United States)

2013-06-15

Tapering of U–Mo alloy fuel at the end of plates is attributed to lateral mass transfer by fission induced creep, by which fuel mass is relocated away from the fuel end region where fission product induced fuel swelling is in fact the highest. This mechanism permits U–Mo fuel to achieve high burnup by effectively relieving stresses at the fuel end region, where peak stresses are otherwise expected because peak fission product induced fuel swelling occurs there. ABAQUS FEA was employed to examine whether the observed phenomenon can be simulated using physical–mechanical data available in the literature. The simulation results obtained for several plates with different fuel fabrication and loading scheme showed that the measured data were able to be simulated with a reasonable creep rate coefficient. The obtained creep rate constant lies between values for pure uranium and MOX, and is greater than all other ceramic uranium fuels.

Radioactive ion beams produced by neutron-induced fission at ISOLDE

CERN Document Server

Catherall, R; Gilardoni, S S; Köster, U

2003-01-01

The production rates of neutron-rich fission products for the next-generation radioactive beam facility EURISOL are mainly limited by the maximum amount of power deposited by protons in the target. An alternative approach is to use neutron beams to induce fission in actinide targets. This has the advantage of reducing: the energy deposited by the proton beam in the target; contamination from neutron-deficient isobars that would be produced by spallation; and mechanical stress on the target. At ISOLDE CERN, tests have been made on standard ISOLDE actinide targets using fast neutron bunches produced by bombarding thick, high-Z metal converters with 1 and 1.4 GeV proton pulses. This paper reviews the first applications of converters used at ISOLDE. It highlights the different geometries and the techniques used to compare fission yields produced by the proton beam directly on the target with neutron-induced fission. Results from the six targets already tested, namely UC2/graphite and ThO2 targets with tungsten an...

Fission fragment angular distributions in proton-induced fission of 209Bi (p,f) and 197Au (p,f)

International Nuclear Information System (INIS)

Soheily, S.; Noshad, H.; Lamehi-Rashti, M.

2002-01-01

The fission fragment angular distributions have been measured for proton-induced fission of 209 B i and 197 A u nuclei using surface barrier detectors at several energies between 25 MeV and 30 MeV. The experimental anisotropies are found to be in agreement with the predictions of the Standard Saddle-Point Statistical Model. The fission cross sections of 209 B i and 197 A u nuclei were also measured and compared with the previous works

Fission fragment yields and total kinetic energy release in neutron-induced fission of235,238U,and239Pu

Science.gov (United States)

Tovesson, F.; Duke, D.; Geppert-Kleinrath, V.; Manning, B.; Mayorov, D.; Mosby, S.; Schmitt, K.

2018-03-01

Different aspects of the nuclear fission process have been studied at Los Alamos Neutron Science Center (LANSCE) using various instruments and experimental techniques. Properties of the fragments emitted in fission have been investigated using Frisch-grid ionization chambers, a Time Projection Chamber (TPC), and the SPIDER instrument which employs the 2v-2E method. These instruments and experimental techniques have been used to determine fission product mass yields, the energy dependent total kinetic energy (TKE) release, and anisotropy in neutron-induced fission of U-235, U-238 and Pu-239.

Preliminary results of total kinetic energy modelling for neutron-induced fission

International Nuclear Information System (INIS)

Visan, I.; Giubega, G.; Tudora, A.

2015-01-01

The total kinetic energy as a function of fission fragments mass TKE(A) is an important quantity entering in prompt emission calculations. The experimentally distributions of TKE(A) are referring to a limited number of fission systems and incident energies. In the present paper, a preliminary model for TKE calculation in neutron induced fission system is presented. The range of fission fragments is chosen as in the Point by Point treatment. The model needs as input only mass excesses and deformation parameters taken from available nuclear databases being based on the following approximations: total excitation energy of fully accelerated fission fragments TXE is calculated from energy balance of neutron-induced fission systems as sum of the total excitation energy at scission E*sciss and deformation energy Edef. The deformation energy at scission is given by minimizing the potential energy at the scission configuration. At the scission point, the fission system is described by two spheroidal fragments nearly touching by a pre-scission distance or neck caused by the nuclear forces between fragments. Therefore, the Columbian repulsion depending on neck and, consequently, on the fragments deformation at scission, is essentially in TKE determination. An approximation is made based on the fission modes. For the very symmetric fission, the dominant super long channel is characterized by long distance between fragments leading to low TKE values. Due to magic and double-magic shells closure, the dominant S1 fission mode for pairs with heavy fragment mass AH around 130-134 is characterized by spherical heavy fragment shape and easily deformed light fragment. The nearly spherical shape of the complementary fragments are characterized by minimum distance, and consequently to maximum TKE values. The results obtained for TKE(A) are in good agreement with existing experimental data for many neutron induced fission systems, e.g. ''2''3''3&apos

Mitochondrial Metabolism in Aging Heart

Science.gov (United States)

Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

2016-01-01

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

Tools for assessing mitochondrial dynamics in mouse tissues and neurodegenerative models

Science.gov (United States)

Pham, Anh H.

Mitochondria are dynamic organelles that undergo membrane fusion and fission and transport. The dynamic properties of mitochondria are important for regulating mitochondrial function. Defects in mitochondrial dynamics are linked neurodegenerative diseases and affect the development of many tissues. To investigate the role of mitochondrial dynamics in diseases, versatile tools are needed to explore the physiology of these dynamic organelles in multiple tissues. Current tools for monitoring mitochondrial dynamics have been limited to studies in cell culture, which may be inadequate model systems for exploring the network of tissues. Here, we have generated mouse models for monitoring mitochondrial dynamics in a broad spectrum of tissues and cell types. The Photo-Activatable Mitochondrial (PhAM floxed) line enables Cre-inducible expression of a mitochondrial targeted photoconvertible protein, Dendra2 (mito-Dendra2). In the PhAMexcised line, mito-Dendra2 is ubiquitously expressed to facilitate broad analysis of mitochondria at various developmental processes. We have utilized these models to study mitochondrial dynamics in the nigrostriatal circuit of Parkinson's disease (PD) and in the development of skeletal muscles. Increasing evidences implicate aberrant regulation of mitochondrial fusion and fission in models of PD. To assess the function of mitochondrial dynamics in the nigrostriatal circuit, we utilized transgenic techniques to abrogate mitochondrial fusion. We show that deletion of the Mfn2 leads to the degeneration of dopaminergic neurons and Parkinson's-like features in mice. To elucidate the dynamic properties of mitochondria during muscle development, we established a platform for examining mitochondrial compartmentalization in skeletal muscles. This model system may yield clues to the role of mitochondrial dynamics in mitochondrial myopathies.

Studies on the reaction mechanism of the muon induced nuclear fission

International Nuclear Information System (INIS)

Mutius, R. von.

1985-01-01

The mass and energy distribution of the fission fragments after muon induced nuclear fission allows the determination of the mean excitation energy of the fissioning nucleus after muon capture. By the systematic comparison with a mass distribution of a corresponding reaction for the first time for this an accuracy of about 1 MeV could be reached. Theoretical calculations on the excitation probability in the muon capture allow in connection with the fission probability an estimating calculation of this energy. The experimental result represents by this a test criterium for the valuation of the theoretical calculation. The measured probabilities for the occurrence of radiationless transitions in the muonic γ cascade of 237 Np permit an indirect experimental determination of the barrier enhancement which causes the muon present during the fission process. The value found for this extends to 0.75+-0.1 MeV. A change of the mass distribution by the muon cannot be detected in the nuclides 235 U, 237 Np, and 242 Pu studied here. Only the mean total kinetic energy of the fission products is reduced in these three nuclides in the prompt μ - induced fission by 1 to 2 MeV. For this result the incomplete screening of the nuclear charge during the fission process is made responsible. A mass dependence of this reduction has not been stated. Because the muon has appearently no influence on the mass splitting it can be valied as nearly ideal particle in order to study the hitherto little studied dynamics of the fission process. (orig.) [de

Antiproton Induced Fission and Fragmentation of Nuclei

CERN Multimedia

2002-01-01

The annihilation of slow antiprotons with nuclei results in a large highly localized energy deposition primarily on the nuclear surface. \\\\ \\\\ The study of antiproton induced fission and fragmentation processes is expected to yield new information on special nuclear matter states, unexplored fission modes, multifragmentation of nuclei, and intranuclear cascades.\\\\ \\\\ In order to investigate the antiproton-nucleus interaction and the processes following the antiproton annihilation at the nucleus, we propose the following experiments: \\item A)~Measurement of several fragments from fission and from multifragmentation in coincidence with particle spectra, especially neutrons and kaons. \\item B)~Precise spectra of $\\pi$, K, n, p, d and t with time-of-flight techniques. \\item C)~Installation of the Berlin 4$\\pi$ neutron detector with a 4$\\pi$ Si detector placed inside for fragments and charged particles. This yields neutron multiplicity distributions and consequently distributions of thermal excitation energies and...

p- and n-induced U-fission tracks as possible error sources in the fission track dating of extraterrestric samples

International Nuclear Information System (INIS)

Thiel, K.

1975-01-01

Using the fission track dating method by means of uranium fission tracks in meteorites and moon samples (according to the successful Apollo and Luna missions), special problems arise, as the samples frequently have a very great age and were subjected to the inmediate effect of primary cosmic radiation. To determine the share of induced fission tracks, an extended 'cosmic ray' simulation experiment was carried out on the p-synchrocyclotron in CERN, Geneva; the performance and results of the test with the proton flux and U fission track measurements are dealt with in detail. (HK/LH) [de

Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint.

Science.gov (United States)

Yamamori, Tohru; Yasui, Hironobu; Yamazumi, Masayuki; Wada, Yusuke; Nakamura, Yoshinari; Nakamura, Hideo; Inanami, Osamu

2012-07-15

Whereas ionizing radiation (Ir) instantaneously causes the formation of water radiolysis products that contain some reactive oxygen species (ROS), ROS are also suggested to be released from biological sources in irradiated cells. It is now becoming clear that these ROS generated secondarily after Ir have a variety of biological roles. Although mitochondria are assumed to be responsible for this Ir-induced ROS production, it remains to be elucidated how Ir triggers it. Therefore, we conducted this study to decipher the mechanism of Ir-induced mitochondrial ROS production. In human lung carcinoma A549 cells, Ir (10 Gy of X-rays) induced a time-dependent increase in the mitochondrial ROS level. Ir also increased mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production, suggesting upregulation of the mitochondrial electron transport chain (ETC) function after Ir. Although we found that Ir slightly enhanced mitochondrial ETC complex II activity, the complex II inhibitor 3-nitropropionic acid failed to reduce Ir-induced mitochondrial ROS production. Meanwhile, we observed that the mitochondrial mass and mitochondrial DNA level were upregulated after Ir, indicating that Ir increased the mitochondrial content of the cell. Because irradiated cells are known to undergo cell cycle arrest under control of the checkpoint mechanisms, we examined the relationships between cell cycle and mitochondrial content and cellular oxidative stress level. We found that the cells in the G2/M phase had a higher mitochondrial content and cellular oxidative stress level than cells in the G1 or S phase, regardless of whether the cells were irradiated. We also found that Ir-induced accumulation of the cells in the G2/M phase led to an increase in cells with a high mitochondrial content and cellular oxidative stress level. This suggested that Ir upregulated mitochondrial ETC function and mitochondrial content, resulting in mitochondrial ROS production, and that

Measurement of the neutron-induced fission cross-section of 240,242Pu

International Nuclear Information System (INIS)

Salvador-Castineira, P.; Hambsch, F.J.; Brys, T.; Oberstedt, S.; Vidali, M.; Pretel, C.

2014-01-01

Fast spectrum neutron-induced fission cross-section data for transuranic isotopes are in high demand in the nuclear data community. In particular, highly accurate data are needed for the new Generation-IV nuclear applications. The aim is to obtain precise neutron-induced fission cross-sections for 240 Pu and 242 Pu. In this context accurate data on spontaneous fission half-lives have also been measured. To minimise the total uncertainty on the fission cross-sections the detector efficiency has been studied in detail. Both isotopes have been measured using a twin Frisch-grid ionisation chamber (TFGIC) due to its superiority compared to other detector systems in view of radiation hardness, 2 x 2π solid angle coverage and very good energy resolution. (authors)

A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.

Directory of Open Access Journals (Sweden)

Houman Ashrafian

2010-06-01

Full Text Available Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM. However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease.

Amelioration of Mitochondrial Dysfunction-Induced Insulin Resistance in Differentiated 3T3-L1 Adipocytes via Inhibition of NF-κB Pathways

Directory of Open Access Journals (Sweden)

Mohamad Hafizi Abu Bakar

2014-12-01

Full Text Available A growing body of evidence suggests that activation of nuclear factor kappa B (NF-κB signaling pathways is among the inflammatory mechanism involved in the development of insulin resistance and chronic low-grade inflammation in adipose tissues derived from obese animal and human subjects. Nevertheless, little is known about the roles of NF-κB pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-κB inhibitor upon mitochondrial dysfunction-induced insulin resistance in 3T3-L1 adipocytes. Celastrol ameliorates mitochondrial dysfunction by altering mitochondrial fusion and fission in adipocytes. The levels of oxidative DNA damage, protein carbonylation and lipid peroxidation were down-regulated. Further, the morphology and quantification of intracellular lipid droplets revealed the decrease of intracellular lipid accumulation with reduced lipolysis. Moreover, massive production of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β were markedly depleted. Insulin-stimulated glucose uptake activity was restored with the enhancement of insulin signaling pathways. This study signified that the treatments modulated towards knockdown of NF-κB transcription factor may counteract these metabolic insults exacerbated in our model of synergy between mitochondrial dysfunction and inflammation. These results demonstrate for the first time that NF-κB inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes.

Actinide neutron-induced fission cross section measurements at LANSCE

Energy Technology Data Exchange (ETDEWEB)

Tovesson, Fredrik K [Los Alamos National Laboratory; Laptev, Alexander B [Los Alamos National Laboratory; Hill, Tony S [INL

2010-01-01

Fission cross sections of a range of actinides have been measured at the Los Alamos Neutron Science Center (LANSCE) in support of nuclear energy applications in a wide energy range from sub-thermal energies up to 200 MeV. A parallel-plate ionization chamber are used to measure fission cross sections ratios relative to the {sup 235}U standard while incident neutron energies are determined using the time-of-flight method. Recent measurements include the {sup 233,238}U, {sup 239-242}Pu and {sup 243}Am neutron-induced fission cross sections. Obtained data are presented in comparison with ex isting evaluations and previous data.

Pion-induced fission of 209Bi and 119Sn: measurements, calculations, analyses and comparison

International Nuclear Information System (INIS)

Rana, M.A.; Sher, G.; Manzoor, S.; Shehzad, M.I.

2011-01-01

Cross-sections for the π - -induced fission of 209 Bi and 119 Sn have been measured using the most sensitive CR-39 solid-state nuclear track detector. In experiments, target–detector stacks were exposed to negative pions of energy 500, 672, 1068, and 1665 MeV at the Brookhaven National Laboratory, USA. An important aspect of the present paper is the comparison of pion-induced fission fragment spectra of above mentioned nuclei with the spontaneous fission fragment spectra of 252 Cf. This comparison is made in terms of fission fragment track lengths in the CR-39 detectors. Measurement results are compared with calculations of Monte Carlo and statistical weight functions methods using the computer code CEM95. Agreement between measurements and calculations is fairly good for 209 Bi target nuclei whereas it is indigent for the case of 119 Sn. The possibilities of the trustworthy calculations, using the computer code CEM95, comparable with measurements of pion-induced fission in intermediate and heavy nuclei are explored by employing various systematics available in the code. Energy dependence of pion-induced fission in 119 Sn and 209 Bi is analyzed employing a newly defined parameter geometric-size-normalized fission cross-section (χ f g ). It is found that the collective nuclear excitations, which may lead to fission, become more probable for both 209 Bi and 119 Sn nuclei with increasing energy of negative pions from 500 to 1665 MeV. (author)

Active-interrogation measurements of fast neutrons from induced fission in low-enriched uranium

International Nuclear Information System (INIS)

Dolan, J.L.; Marcath, M.J.; Flaska, M.; Pozzi, S.A.; Chichester, D.L.; Tomanin, A.; Peerani, P.

2014-01-01

A detection system was designed with MCNPX-PoliMi to measure induced-fission neutrons from U-235 and U-238 using active interrogation. Measurements were then performed with this system at the Joint Research Centre in Ispra, Italy on low-enriched uranium samples. Liquid scintillators measured induced fission neutrons to characterize the samples in terms of their uranium mass and enrichment. Results are presented to investigate and support the use of organic liquid scintillators with active interrogation techniques to characterize uranium containing materials. -- Highlights: • We studied low-enriched uranium using active-interrogation experiments including a deuterium–tritium neutron generator and an americium–lithium isotopic neutron source. • Liquid scintillators measured induced-fission neutrons from the active-interrogation methods. • Fast-neutron (DT) and thermal-neutron (Am–Li) interrogation resulted in the measurement of trends in uranium mass and 235 U enrichment respectively. • MCNPX-PoliMi, the Monte Carlo transport code, simulated the measured induced-fission neutron trends in the liquid scintillators

Active-interrogation measurements of fast neutrons from induced fission in low-enriched uranium

Energy Technology Data Exchange (ETDEWEB)

Dolan, J.L., E-mail: jldolan@umich.edu [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States); Marcath, M.J.; Flaska, M.; Pozzi, S.A. [Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109 (United States); Chichester, D.L. [Idaho National Laboratory, Idaho Falls, ID 83415 (United States); Tomanin, A.; Peerani, P. [European Commission, Joint Research Centre, Institute for Transuranium Elements, Ispra (Italy)

2014-02-21

A detection system was designed with MCNPX-PoliMi to measure induced-fission neutrons from U-235 and U-238 using active interrogation. Measurements were then performed with this system at the Joint Research Centre in Ispra, Italy on low-enriched uranium samples. Liquid scintillators measured induced fission neutrons to characterize the samples in terms of their uranium mass and enrichment. Results are presented to investigate and support the use of organic liquid scintillators with active interrogation techniques to characterize uranium containing materials. -- Highlights: • We studied low-enriched uranium using active-interrogation experiments including a deuterium–tritium neutron generator and an americium–lithium isotopic neutron source. • Liquid scintillators measured induced-fission neutrons from the active-interrogation methods. • Fast-neutron (DT) and thermal-neutron (Am–Li) interrogation resulted in the measurement of trends in uranium mass and {sup 235}U enrichment respectively. • MCNPX-PoliMi, the Monte Carlo transport code, simulated the measured induced-fission neutron trends in the liquid scintillators.

Measurements of fast neutron-induced fission data of Np-237

Energy Technology Data Exchange (ETDEWEB)

Win, Than; Saito, Keiichiro; Baba, Mamoru; Iwasaki, Tomohiko; Ibaraki, Masanobu; Miura, Takako; Sanami, Toshiya; Nauchi, Yasushi; Hirakawa, Naohiro [Tohoku Univ., Sendai (Japan). Faculty of Engineering

1998-03-01

We have performed the following measurements for {sup 237}Np using the 4.5 MV Dynamitron accelerator of Tohoku University as the pulsed neutron source: (1) Prompt fission neutron spectrum for 0.62 MeV incident neutrons, and (2) Neutron-Induced fission cross-section between 10 and 100 keV. The prompt fission neutron spectrum was measured using TOF method with a heavily shielded NE213 scintillation detector. The Maxwellian temperature T{sub m} derived is 1.28 MeV, which is lower than that of 1.38 MeV in JENDL-3.2. The fission cross sections were measured between 10 - 100 keV. The results are between JENDL-3.2 and ENDF/B-VI. (author)

Mass-yield distributions of fission products from 20, 32, and 45 MeV proton-induced fission of 232Th

Science.gov (United States)

Naik, H.; Goswami, A.; Kim, G. N.; Kim, K.; Suryanarayana, S. V.

2013-10-01

The yields of various fission products in the 19.6, 32.2, and 44.8 MeV proton-induced fission of 232Th have been determined by recoil catcher and an off-line γ-ray spectrometric technique using the BARC-TIFR Pelletron in India and MC-50 cyclotron in Korea. The mass-yield distributions were obtained from the fission product yield using the charge distribution corrections. The peak-to-valley (P/V) ratio of the present work and that of literature data for 232Th(p,f) and 238U(p,f) were obtained from the mass yield distribution. The present and the existing literature data for 232Th(p,f), 232Th(n,f), and 232Th( γ,f) at various energies were compared with those for 238U(p,f), 238U(n,f), and 238U( γ,f) to examine the probable nuclear structure effect. The role of Th-anomaly on the peak-to-valley ratio in proton-, neutron-, and photon-induced fission of 232Th was discussed with the similar data in 238U. On the other hand, the fine structure in the mass yield distributions of the fissioning systems at various excitation energies has been explained from the point of standard I and II asymmetric mode of fission besides the probable role of even-odd effect, A/ Z ratio, and fissility parameter.

A possible mechanism in heavy ion induced reactions: 'fast fission process'

International Nuclear Information System (INIS)

Borderie, B.; Gardes, D.; Berlanger, M.

1980-01-01

The influence of the orbital angular momentum l on the mass distribution of fission fragments is studied, both on previously available data on heavy ion induced fission and in new specifically planned experiments: systems 40 Ar + 165 Ho and 24 Mg + 181 Ta at bombarding energies ranging from 180 up to 391 MeV and leading to the same fissionning nucleus 205 At wigh different l distributions. When l values corresponding to a vanished fission barrier are reached, the mass distribution broadens. This suggest the existence of a specific process, 'fast fission', at l-values leading to compound nucleus formation and deep inelastic collisions, respectively. This process and its conditions of occurrence are discussed; of special interest are the correlated differences between the limitations to the fission cross-section and the fission mass distributions broadenings, respectively, for the Ar + Ho and Mg + Ta systems

A receptor tyrosine kinase inhibitor, Tyrphostin A9 induces cancer cell death through Drp1 dependent mitochondria fragmentation

International Nuclear Information System (INIS)

Park, So Jung; Park, Young Jun; Shin, Ji Hyun; Kim, Eun Sung; Hwang, Jung Jin; Jin, Dong-Hoon; Kim, Jin Cheon; Cho, Dong-Hyung

2011-01-01

Highlights: → We screened and identified Tyrphostin A9, a receptor tyrosine kinase inhibitor as a strong mitochondria fission inducer. → Tyrphostin A9 treatment promotes mitochondria dysfunction and contributes to cytotoxicity in cancer cells. → Tyrphostin A9 induces apoptotic cell death through a Drp1-mediated pathway. → Our studies suggest that Tyrphostin A9 induces mitochondria fragmentation and apoptotic cell death via Drp1 dependently. -- Abstract: Mitochondria dynamics controls not only their morphology but also functions of mitochondria. Therefore, an imbalance of the dynamics eventually leads to mitochondria disruption and cell death. To identify specific regulators of mitochondria dynamics, we screened a bioactive chemical compound library and selected Tyrphostin A9, a tyrosine kinase inhibitor, as a potent inducer of mitochondrial fission. Tyrphostin A9 treatment resulted in the formation of fragmented mitochondria filament. In addition, cellular ATP level was decreased and the mitochondrial membrane potential was collapsed in Tyr A9-treated cells. Suppression of Drp1 activity by siRNA or over-expression of a dominant negative mutant of Drp1 inhibited both mitochondrial fragmentation and cell death induced by Tyrpohotin A9. Moreover, treatment of Tyrphostin A9 also evoked mitochondrial fragmentation in other cells including the neuroblastomas. Taken together, these results suggest that Tyrphostin A9 induces Drp1-mediated mitochondrial fission and apoptotic cell death.

The Effect of Stiffness Parameter on Mass Distribution in Heavy-Ion Induced Fission

Science.gov (United States)

Soheyli, Saeed; Khalil Khalili, Morteza; Ashrafi, Ghazaaleh

2018-06-01

The stiffness parameter of the composite system has been studied for several heavy-ion induced fission reactions without the contribution of non-compound nucleus fission events. In this research, determination of the stiffness parameter is based on the comparison between the experimental data on the mass widths of fission fragments and those predicted by the statistical model treatments at the saddle and scission points. Analysis of the results shows that for the induced fission reactions of different targets by the same projectile, the stiffness parameter of the composite system decreases with increasing the fissility parameter, as well as with increasing the mass number of the compound nucleus. This parameter also exhibits a similar behavior for the reactions of a given target induced by different projectiles. As expected, nearly same stiffness values are obtained for different reactions leading to the same compound nucleus.

Neutron induced fission of 237Np – status, challenges and opportunities

Directory of Open Access Journals (Sweden)

Ruskov Ivan

2018-01-01

Full Text Available Nowadays, there is an increased interest in a complete study of the neutron-induced fission of 237Np. This is due to the need of accurate and reliable nuclear data for nuclear science and technology. 237Np is generated (and accumulated in the nuclear reactor core during reactor operation. As one of the most abundant long-lived isotopes in spent fuel (“waste”, the incineration of 237Np becomes an important issue. One scenario for burning of 237Np and other radio-toxic minor actinides suggests they are to be mixed into the fuel of future fast-neutron reactors, employing the so-called transmutation and partitioning technology. For testing present fission models, which are at the basis of new generation nuclear reactor developments, highly accurate and detailed neutron-induced nuclear reaction data is needed. However, the EXFOR nuclear database for 237Np on neutron-induced capture cross-section, σγ, and fission cross-section, σf, as well as on the characteristics of capture and fission resonance parameters (Γγ, Γf, σoΓf, fragments mass-energy yield distributions, multiplicities of neutrons vn and γ-rays vγ, has not been updated for decades.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

Science.gov (United States)

Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Neutron induced current pulses in fission chambers

International Nuclear Information System (INIS)

Taboas, A.L.; Buck, W.L.

1978-01-01

The mechanism of neutron induced current pulse generation in fission chambers is discussed. By application of the calculated detector transfer function to proposed detector current pulse shapes, and by comparison with actually observed detector output voltage pulses, a credible, semi-empirical, trapezoidal pulse shape of chamber current is obtained

Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

Science.gov (United States)

Long, Aaron; Klimova, Nina; Kristian, Tibor

2017-10-01

NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Published by Elsevier Ltd.

Mitochondrial dysfunction in lyssavirus-induced apoptosis.

Science.gov (United States)

Gholami, Alireza; Kassis, Raïd; Real, Eléonore; Delmas, Olivier; Guadagnini, Stéphanie; Larrous, Florence; Obach, Dorothée; Prevost, Marie-Christine; Jacob, Yves; Bourhy, Hervé

2008-05-01

Lyssaviruses are highly neurotropic viruses associated with neuronal apoptosis. Previous observations have indicated that the matrix proteins (M) of some lyssaviruses induce strong neuronal apoptosis. However, the molecular mechanism(s) involved in this phenomenon is still unknown. We show that for Mokola virus (MOK), a lyssavirus of low pathogenicity, the M (M-MOK) targets mitochondria, disrupts the mitochondrial morphology, and induces apoptosis. Our analysis of truncated M-MOK mutants suggests that the information required for efficient mitochondrial targeting and dysfunction, as well as caspase-9 activation and apoptosis, is held between residues 46 and 110 of M-MOK. We used a yeast two-hybrid approach, a coimmunoprecipitation assay, and confocal microscopy to demonstrate that M-MOK physically associates with the subunit I of the cytochrome c (cyt-c) oxidase (CcO) of the mitochondrial respiratory chain; this is in contrast to the M of the highly pathogenic Thailand lyssavirus (M-THA). M-MOK expression induces a significant decrease in CcO activity, which is not the case with M-THA. M-MOK mutations (K77R and N81E) resulting in a similar sequence to M-THA at positions 77 and 81 annul cyt-c release and apoptosis and restore CcO activity. As expected, the reverse mutations, R77K and E81N, introduced in M-THA induce a phenotype similar to that due to M-MOK. These features indicate a novel mechanism for energy depletion during lyssavirus-induced apoptosis.

Studies of Fission-Induced Surface Damage in Actinides Using Ultracold Neutrons

Energy Technology Data Exchange (ETDEWEB)

Broussard, Leah J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2014-03-05

This report describes the results of the fission-induced actinide studies at LANL. Previously, there was no fission data at these energies though there were initial characterizations of UCN energy dependence and material thickness. The proof of principle was demonstrated and the initial characterizations of sputtered rates, angular and size distribution are underway.

Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

Directory of Open Access Journals (Sweden)

Rui Guo

2010-01-01

Full Text Available Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p. for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways were examined.Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2 (*-. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF.Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

Science.gov (United States)

Guo, Rui; Ren, Jun

2010-01-18

Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

Fission properties of actinide nuclei from proton-induced fission at 26.5 and 62.9 MeV incident proton energies

International Nuclear Information System (INIS)

Demetriou, P.; Keutgen, Th.; Prieels, R.; El Masri, Y.

2010-01-01

Fission properties of proton-induced fission on 232 Th, 237 Np, 238 U, 239 Pu, and 241 Am targets, measured at the Louvain-la-Neuve cyclotron facility at proton energies of 26.5 and 62.9 MeV, are compared with the predictions of the state-of-the-art nuclear reaction code talys. The code couples the multimodal random neck-rupture model with the pre-equilibrium exciton and statistical models to predict fission fragment mass yields, pre- and post-scission neutron multiplicities, and total fission cross sections in a consistent approach. The sensitivity of the calculations to the input parameters of the code and possible improvements are discussed in detail.

Comparison of 252Cf time correlated induced fission with AmLi induced fission on fresh MTR reserach reactor fuel

Energy Technology Data Exchange (ETDEWEB)

Joshi, Jay Prakash [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-05-01

The objectives of this project are to calibrate the Advanced Experimental Fuel Counter (AEFC), benchmark MCNP simulations using experimental results, investigate the effects of change in fuel assembly geometry, and finally to show the boost in doubles count rates with 252Cf active soruces due to the time correlated induced fission (TCIF) effect.

Simultaneous measurement of fission fragments and prompt neutrons for thermal neutron-induced fission of U-235

Energy Technology Data Exchange (ETDEWEB)

Nishio, Katsuhisa; Yamamoto, Hideki; Kimura, Itsuro; Nakagome, Yoshihiro [Kyoto Univ. (Japan)

1997-03-01

Simultaneous measurement of fission fragments and prompt neutrons following the thermal neutron induced fission of U-235 has been performed in order to obtain the neutron multiplicity (v) and its emission energy ({eta}) against the specified mass (m{sup *}) and the total kinetic energy (TKE). The obtained value of -dv/dTKE(m{sup *}) showed a saw-tooth distribution. The average neutron energy <{eta}>(m{sup *}) had a distribution with a reflection symmetry around the half mass division. The measurement also gave the level density parameters of the specified fragment, a(m{sup *}), and this parameters showed a saw-tooth trend too. The analysis by a phenomenological description of this parameters including the shell and collective effects suggested the existence of a collective motion of the fission fragments. (author)

Distribution of mitochondrial nucleoids upon mitochondrial network fragmentation and network reintegration in HEPG2 cells

Czech Academy of Sciences Publication Activity Database

Tauber, Jan; Dlasková, Andrea; Šantorová, Jitka; Smolková, Katarína; Alán, Lukáš; Špaček, Tomáš; Plecitá-Hlavatá, Lydie; Ježek, Petr

2013-01-01

Roč. 45, č. 3 (2013), s. 593-603 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204; GA ČR(CZ) GAP305/12/1247 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : mitochondrial DNA nucleoids * mitochondrial fission * mitochondrial network fragmentation * mitochondrial network reintegration Subject RIV: ED - Physiology Impact factor: 4.240, year: 2013

Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

Science.gov (United States)

da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

2014-02-01

We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

An evaporation-based model of thermal neutron induced ternary fission of plutonium

International Nuclear Information System (INIS)

Lestone, J.P.

2008-01-01

Ternary fission probabilities for thermal neutron induced fission of plutonium are analyzed within the framework of an evaporation-based model where the complexity of time-varying potentials, associated with the neck collapse, are included in a simplistic fashion. If the nuclear temperature at scission and the fission-neck-collapse time are assumed to be ~ 1.2 MeV and ~ 10 -22 s, respectively, then calculated relative probabilities of ternary-fission light-charged-particle emission follow the trends seen in the experimental data. The ability of this model to reproduce ternary fission probabilities spanning seven orders of magnitude for a wide range of light-particle charges and masses implies that ternary fission is caused by the coupling of an evaporation-like process with the rapid re-arrangement of the nuclear fluid following scission. (author)

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Science.gov (United States)

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

Carbon monoxide alleviates lipopolysaccharide-induced oxidative stress injury through suppressing the expression of Fis1 in NR8383 cells

Energy Technology Data Exchange (ETDEWEB)

Shi, Jia [Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100 (China); Yu, Jian-bo, E-mail: yujianbo11@126.com [Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100 (China); Liu, Wei; Wang, Dan; Zhang, Yuan; Gong, Li-rong; Dong, Shu-an [Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100 (China); Liu, Da-quan [Department of Pharmacology, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin 300100 (China)

2016-11-15

Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics. In addition, as one of the products of heme degradation catalyzed by heme oxygenase, carbon monoxide (CO) possesses powerful protective properties in vivo or in vitro models, such as anti-inflammatory, antioxidant and anti-apoptosis function. However, there is little evidence that CO alleviates oxidative stress damage through altering mitochondrial fission in alveolar macrophages. In the present study, our results showed that CO increased cell vitality, improved mitochondrial SOD activity, reduced reactive oxygen species (ROS) production and inhibited cell apoptosis in NR8383 exposed to LPS. Meanwhile, CO decreased the expression of Fis1, increased mitochondrial membrane potential and sustained elongation of mitochondria in LPS-incubated NR8383. Overall, our study underscored a critical role of CO in suppressing the expression of Fis1 and alleviating LPS- induced oxidative stress damage in alveolar macrophages. - Highlights: • LPS exposure triggered cell injury in NR8383. • CO alleviated LPS-induced oxidative stress damage in alveolar macrophages. • CO inhibited Fis1 levels and improved mitochondrial function in LPS-induced NR8383.

Mass-yield distributions of fission products from 20, 32, and 45 MeV proton-induced fission of {sup 232}Th

Energy Technology Data Exchange (ETDEWEB)

Naik, H.; Goswami, A. [Bhabha Atomic Research Centre, Radiochemistry Division, Mumbai (India); Kim, G.N.; Kim, K. [Kyungpook National University, Department of Physics, Daegu (Korea, Republic of); Suryanarayana, S.V. [Bhabha Atomic Research Centre, Nuclear Physics Division, Mumbai (India)

2013-10-15

The yields of various fission products in the 19.6, 32.2, and 44.8 MeV proton-induced fission of {sup 232}Th have been determined by recoil catcher and an off-line {gamma}-ray spectrometric technique using the BARC-TIFR Pelletron in India and MC-50 cyclotron in Korea. The mass-yield distributions were obtained from the fission product yield using the charge distribution corrections. The peak-to-valley (P/V) ratio of the present work and that of literature data for {sup 232}Th(p,f) and {sup 238}U(p,f) were obtained from the mass yield distribution. The present and the existing literature data for {sup 232}Th(p,f), {sup 232}Th(n,f), and {sup 232}Th({gamma},f) at various energies were compared with those for {sup 238}U(p,f), {sup 238}U(n,f), and {sup 238}U({gamma},f) to examine the probable nuclear structure effect. The role of Th-anomaly on the peak-to-valley ratio in proton-, neutron-, and photon-induced fission of {sup 232}Th was discussed with the similar data in {sup 238}U. On the other hand, the fine structure in the mass yield distributions of the fissioning systems at various excitation energies has been explained from the point of standard I and II asymmetric mode of fission besides the probable role of even-odd effect, A/Z ratio, and fissility parameter. (orig.)

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

Directory of Open Access Journals (Sweden)

Carola Stockburger

2016-01-01

Full Text Available The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Radiochemical studies on fission

Energy Technology Data Exchange (ETDEWEB)

None

1973-07-01

Research progress is reported on nuclear chemistry; topics considered include: recoil range and kinetic energy distribution in the thermal neutron ftssion of /sup 245/Cm; mass distribution and recoil range measurements in the reactor neutron-induced fission of /sup 232/U; fission yields in the thermal neutron fission of /sup 241/PU highly asymmetric binary fission of uranium induced by reactor neutrons; and nuclear charge distribution in low energy fission. ( DHM)

Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

International Nuclear Information System (INIS)

Chen, Shang-Der; Lin, Tsu-Kung; Yang, Ding-I.; Lee, Su-Ying; Shaw, Fu-Zen; Liou, Chia-Wei; Chuang, Yao-Chung

2015-01-01

Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield

Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

Energy Technology Data Exchange (ETDEWEB)

Chen, Shang-Der, E-mail: chensd@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Lin, Tsu-Kung [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Yang, Ding-I. [Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan (China); Lee, Su-Ying [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Shaw, Fu-Zen [Department of Psychology, National Cheng Kung University, Tainan, Taiwan (China); Liou, Chia-Wei [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Chuang, Yao-Chung, E-mail: ycchuang@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China)

2015-05-01

Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield.

Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity

International Nuclear Information System (INIS)

Oliveira, Paulo J.; Bjork, James A.; Santos, Maria S.; Leino, Richard L.; Froberg, M. Kent; Moreno, Antonio J.; Wallace, Kendall B.

2004-01-01

The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a β-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its β-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a β-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its β-adrenergic receptor antagonism

Mitochondrial Fusion Proteins and Human Diseases

Directory of Open Access Journals (Sweden)

Michela Ranieri

2013-01-01

Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

Photon-induced Fission Product Yield Measurements on 235U, 238U, and 239Pu

Science.gov (United States)

Krishichayan, Fnu; Bhike, M.; Tonchev, A. P.; Tornow, W.

2015-10-01

During the past three years, a TUNL-LANL-LLNL collaboration has provided data on the fission product yields (FPYs) from quasi-monoenergetic neutron-induced fission of 235U, 238U, and 239Pu at TUNL in the 0.5 to 15 MeV energy range. Recently, we have extended these experiments to photo-fission. We measured the yields of fission fragments ranging from 85Kr to 147Nd from the photo-fission of 235U, 238U, and 239Pu using 13-MeV mono-energetic photon beams at the HIGS facility at TUNL. First of its kind, this measurement will provide a unique platform to explore the effect of the incoming probe on the FPYs, i.e., photons vs. neutrons. A dual-fission ionization chamber was used to determine the number of fissions in the targets and these samples (along with Au monitor foils) were gamma-ray counted in the low-background counting facility at TUNL. Details of the experimental set-up and results will be presented and compared to the FPYs obtained from neutron-induced fission at the same excitation energy of the compound nucleus. Work supported in part by the NNSA-SSAA Grant No. DE-NA0001838.

Recent results in heavy-ion-induced fission

International Nuclear Information System (INIS)

Plasil, F.; Awes, T.C.; Cheynis, B.

1984-01-01

A systematic investigation of angular-momentum-dependent fission barriers has been completed. Fission excitation functions were measured for the compound nuclei 153 Tb, 158 Er, 181 Re, 186 Os, and 204 206 208 210 Po. In the case of 153 Tb and 181 Re, evaporation residue cross sections were also measured. With the exception of some of the Po systems, two to five different reactions were used to produce the same compound nucleus with projectiles ranging from 9 Be to 64 Ni. 12 C reactions with 174 Yb, 198 Pt, and 238 U at energies from 95 to 291 MeV; 16 O reactions with 142 Nd, 170 Er, 192 Os, and 238 U at energies from 140 to 315 Mev; 32 S reactions with 126 Te, 144 Nd, and 238 U at energies from 350 to 700 MeV; and 58 Ni reactions with 96 Zr, 116 Cd, and 238 U at 352 and 875 MeV have also been studied. Also, fission fragment angular distributions were measured for the above 12 C- and 16 O-induced reactions. The results were analyzed in terms of saddle-point moments of inertia obtained from the RFRM

Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction

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Seo, Kyuhwa; Seo, Suho; Han, Jae Yun; Ki, Sung Hwan; Shin, Sang Mi, E-mail: smshin@chosun.ac.kr

2014-10-15

Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. - Highlights: • Resveratrol decreased methylglyoxal-induced apoptosis. • Resveratrol attenuated GSH depletion and ROS production promoted by methylglyoxal. • Resveratrol restored the mitochondrial function by Sestrin2 induction. • Induction of Sestrin2

Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction

International Nuclear Information System (INIS)

Seo, Kyuhwa; Seo, Suho; Han, Jae Yun; Ki, Sung Hwan; Shin, Sang Mi

2014-01-01

Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. - Highlights: • Resveratrol decreased methylglyoxal-induced apoptosis. • Resveratrol attenuated GSH depletion and ROS production promoted by methylglyoxal. • Resveratrol restored the mitochondrial function by Sestrin2 induction. • Induction of Sestrin2

Mitochondrial dynamics in mammalian health and disease.

Science.gov (United States)

Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

2009-07-01

The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

Determination of relative krypton fission product yields from 14 MeV neutron induced fission of 238U at the National Ignition Facility.

Science.gov (United States)

Edwards, E R; Cassata, W S; Velsko, C A; Yeamans, C B; Shaughnessy, D A

2016-11-01

Precisely-known fission yield distributions are needed to determine a fissioning isotope and the incident neutron energy in nuclear security applications. 14 MeV neutrons from DT fusion at the National Ignition Facility induce fission in depleted uranium contained in the target assembly hohlraum. The fission yields of Kr isotopes (85m, 87, 88, and 89) are measured relative to the cumulative yield of 88 Kr and compared to previously tabulated values. The results from this experiment and England and Rider are in agreement, except for the 85m Kr/ 88 Kr ratio, which may be the result of incorrect nuclear data.

Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death.

Science.gov (United States)

Parra, Valentina; Moraga, Francisco; Kuzmicic, Jovan; López-Crisosto, Camila; Troncoso, Rodrigo; Torrealba, Natalia; Criollo, Alfredo; Díaz-Elizondo, Jessica; Rothermel, Beverly A; Quest, Andrew F G; Lavandero, Sergio

2013-08-01

Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulate numerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca(2+) overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca(2+) levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca(2+) influx, mitochondrial network fragmentation and loss of the mitochondrial Ca(2+) buffer capacity. These biochemical events increase cytosolic Ca(2+) levels and trigger cardiomyocyte death via the activation of calpains. Copyright © 2013 Elsevier B.V. All rights reserved.

Delayed neutron yield from fast neutron induced fission of 238U

International Nuclear Information System (INIS)

Piksaikin, V.M.; Kazakov, L.E.; Isaev, S.G.; Roshchenko, V.A.; Goverdovski, A.A.; Tertytchnyi, R.G.

2002-01-01

The measurements of the total delayed neutron yield from fast neutron induced fission of 238 U were made. The experimental method based on the periodic irradiation of the fissionable sample by neutrons from a suitable nuclear reaction had been employed. The preliminary results on the energy dependence of the total delayed neutron yield from fission of 238 U are obtained. According to the comparison of experimental data with our prediction based on correlation properties of delayed neutron characteristics, it is concluded that the value of the total delayed neutron yield near the threshold of (n,f) reaction is not a constant. (author)

Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver.

Science.gov (United States)

Theurey, Pierre; Tubbs, Emily; Vial, Guillaume; Jacquemetton, Julien; Bendridi, Nadia; Chauvin, Marie-Agnès; Alam, Muhammad Rizwan; Le Romancer, Muriel; Vidal, Hubert; Rieusset, Jennifer

2016-04-01

Mitochondria-associated endoplasmic reticulum membranes (MAM) play a key role in mitochondrial dynamics and function and in hepatic insulin action. Whereas mitochondria are important regulators of energy metabolism, the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown. In this study, we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse liver. Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A (PP-PP2A) pathway, induced mitochondria fission, and impaired respiration. Blocking MAM reduction counteracted glucose-induced mitochondrial alterations. Furthermore, disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function. This glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice, both characterized by chronic disruption of MAM integrity, mitochondrial fission, and altered mitochondrial respiration. These data indicate that MAM contribute to the hepatic glucose-sensing system, allowing regulation of mitochondria dynamics and function during nutritional transition. Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

Directory of Open Access Journals (Sweden)

Sun Woo Sophie Kang

Full Text Available Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK. When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

Science.gov (United States)

Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

2016-01-01

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload-Induced Mitochondrial Dysfunction and Heart Failure.

Science.gov (United States)

Shirakabe, Akihiro; Zhai, Peiyong; Ikeda, Yoshiyuki; Saito, Toshiro; Maejima, Yasuhiro; Hsu, Chiao-Po; Nomura, Masatoshi; Egashira, Kensuke; Levine, Beth; Sadoshima, Junichi

2016-03-29

Mitochondrial autophagy is an important mediator of mitochondrial quality control in cardiomyocytes. The occurrence of mitochondrial autophagy and its significance during cardiac hypertrophy are not well understood. Mice were subjected to transverse aortic constriction (TAC) and observed at multiple time points up to 30 days. Cardiac hypertrophy developed after 5 days, the ejection fraction was reduced after 14 days, and heart failure was observed 30 days after TAC. General autophagy was upregulated between 1 and 12 hours after TAC but was downregulated below physiological levels 5 days after TAC. Mitochondrial autophagy, evaluated by electron microscopy, mitochondrial content, and Keima with mitochondrial localization signal, was transiently activated at ≈3 to 7 days post-TAC, coinciding with mitochondrial translocation of Drp1. However, it was downregulated thereafter, followed by mitochondrial dysfunction. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of both mitochondrial dysfunction and heart failure after TAC. Injection of Tat-Beclin 1, a potent inducer of autophagy, but not control peptide, on day 7 after TAC, partially rescued mitochondrial autophagy and attenuated mitochondrial dysfunction and heart failure induced by overload. Haploinsufficiency of either drp1 or beclin 1 prevented the rescue by Tat-Beclin 1, suggesting that its effect is mediated in part through autophagy, including mitochondrial autophagy. Mitochondrial autophagy is transiently activated and then downregulated in the mouse heart in response to pressure overload. Downregulation of mitochondrial autophagy plays an important role in mediating the development of mitochondrial dysfunction and heart failure, whereas restoration of mitochondrial autophagy attenuates dysfunction in the heart during pressure overload. © 2016 American Heart Association, Inc.

Training Enhances Immune Cells Mitochondrial Biosynthesis, Fission, Fusion, and Their Antioxidant Capabilities Synergistically with Dietary Docosahexaenoic Supplementation

Directory of Open Access Journals (Sweden)

Carla Busquets-Cortés

2016-01-01

Full Text Available Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA supplementation (1.14 g/day on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs from sportsmen. Subjects were assigned to an intervention (N=9 or placebo groups (N=7 in a randomized double-blind trial. Nutritional intervention significantly increased the DHA content in erythrocyte membranes from the experimental group. No significant differences were reported in terms of circulating PBMCs, Mn-superoxide dismutase protein levels, and their capability to produce reactive oxygen species. The proteins related to mitochondrial dynamics were, in general, increased after an 8-week training and this increase was enhanced by DHA supplementation. The content in mitofusins Mtf-1 and Mtf-2, optic atrophy protein-1 (Opa-1, and mitochondrial transcription factor A (Tfam were significantly higher in the DHA-supplemented group after intervention. Cytochrome c oxidase (COX-IV activity and uncoupling proteins UCP-2 and UCP-3 protein levels were increased after training, with higher UCP-3 levels in the supplemented group. In conclusion, training induced mitochondrial adaptations which may contribute to improved mitochondrial function. This mitochondrial response was modulated by DHA supplementation.

Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

International Nuclear Information System (INIS)

Liu, Cong; Sekine, Shuichi; Ito, Kousei

2016-01-01

Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Liu, Cong; Sekine, Shuichi, E-mail: ssekine@faculty.chiba-u.jp; Ito, Kousei

2016-07-01

Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

Fission product yields from 6 to 9 MeV neutron induced fission of 235U and 238U

International Nuclear Information System (INIS)

Chapman, T.C.

1978-01-01

The yields of 28 mass chains have been measured for fission of 235 U and 238 U induced by neutrons at four different energies from 6.0 to 9.1 MeV. This is the first experimental measurement where sufficient energy resolution was obtained to observe the effect of the onset of second-chance fission in the case of symmetric fission. The 111 Ag results are compared with measurements at other neutron energies and with previous theoretical predictions. Several of the nuclide results are presented in graphical form, and all nuclide results are presented in tabular form, as a function of neutron energy. The mass chains measured range from 84 to 156, and their half-lives range from 18 minutes to 30 years

Mitochondrial Dysfunction in Lyssavirus-Induced Apoptosis▿ †

Science.gov (United States)

Gholami, Alireza; Kassis, Raïd; Real, Eléonore; Delmas, Olivier; Guadagnini, Stéphanie; Larrous, Florence; Obach, Dorothée; Prevost, Marie-Christine; Jacob, Yves; Bourhy, Hervé

2008-01-01

Lyssaviruses are highly neurotropic viruses associated with neuronal apoptosis. Previous observations have indicated that the matrix proteins (M) of some lyssaviruses induce strong neuronal apoptosis. However, the molecular mechanism(s) involved in this phenomenon is still unknown. We show that for Mokola virus (MOK), a lyssavirus of low pathogenicity, the M (M-MOK) targets mitochondria, disrupts the mitochondrial morphology, and induces apoptosis. Our analysis of truncated M-MOK mutants suggests that the information required for efficient mitochondrial targeting and dysfunction, as well as caspase-9 activation and apoptosis, is held between residues 46 and 110 of M-MOK. We used a yeast two-hybrid approach, a coimmunoprecipitation assay, and confocal microscopy to demonstrate that M-MOK physically associates with the subunit I of the cytochrome c (cyt-c) oxidase (CcO) of the mitochondrial respiratory chain; this is in contrast to the M of the highly pathogenic Thailand lyssavirus (M-THA). M-MOK expression induces a significant decrease in CcO activity, which is not the case with M-THA. M-MOK mutations (K77R and N81E) resulting in a similar sequence to M-THA at positions 77 and 81 annul cyt-c release and apoptosis and restore CcO activity. As expected, the reverse mutations, R77K and E81N, introduced in M-THA induce a phenotype similar to that due to M-MOK. These features indicate a novel mechanism for energy depletion during lyssavirus-induced apoptosis. PMID:18321977

Technique of neutron-induced (fission-track) autoradiography with histological detail

International Nuclear Information System (INIS)

Smith, J.M.; Taylor, G.N.; Jee, W.S.S.

1980-01-01

The primary advantage of neutron-induced or fission-track autoradiography compared with conventional autoradiography is that for low concentrations of fissile nuclides prohibitively long exposure times may be avoided. However, it is difficult to produce imaging of biological structures on the neutron-induced autoradiograph which would allow localization of the nuclide histologically. The technique presented circumvents this difficulty using a thin polycarbonate film applied to the histologically stained tissue section mounted on a quartz substrate. After irradiation of the tissue section with an appropriate thermal neutron flux, the fission fragment tracks are revealed by etching the film with KOH. The tracks, superimposed on the stained tissue, may be observed under the light microscope in the same manner as for conventional nuclear emulsion autoradiography

Symmetry of neutron-induced 235U fission at individual resonances. III

Energy Technology Data Exchange (ETDEWEB)

Cowan, G A; Bayhurst, B P; Prestwood, R J; Gilmore, J S; Knobeloch, G W [Los Alamos Scientific Laboratory, University of California, Los Alamos, NM (United States)

1970-05-15

A number of experiments have been described in recent years which document variations in the yields of symmetric or near-symmetric fission products at resonances in 235-U and 239-Pu neutron-induced fission. In the case of 239-Pu fission it has been demonstrated in a statistically significant sample of s-wave neutron resonances (J{sup {pi}} = 0{sup +} or 1{sup +}) that the 0{sup +} levels have a characteristic 115Cd yield which is a factor of four higher than the yield at 1{sup +} levels. The fission widths of the J = 0 levels are larger than the J = 1 levels by a factor of ten. The populations of the two groups are in reasonable agreement with the expected (2J + 1) distributions. Previous efforts to obtain equally detailed data in 235-U fission and 233-U fission by the 'wheel' technique have not been entirely successful due in large part to the high level densities in the epithermal excitation functions of these nuclides and the consequent difficulty in characterizing fission yields in a sufficiently large and well-resolved sample of levels. In a recent 'wheel' experiment (late summer, 1969) vith a 235-U target the energy resolution was sufficiently improved in the region 20 eV-60 eV to allow characterization of a sample of 38 reasonably well-resolved levels by their relative symmetry of fission. (author)

Cerebral energy metabolism during induced mitochondrial dysfunction

DEFF Research Database (Denmark)

Nielsen, T H; Bindslev, TT; Pedersen, S M

2013-01-01

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

Simultaneous measurement of neutron-induced fission and capture cross sections for {sup 241}Am at neutron energies below fission threshold

Energy Technology Data Exchange (ETDEWEB)

Hirose, K., E-mail: hirose.kentaro@jaea.go.jp [Advanced Science Research Center, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki 319-1195 (Japan); Nishio, K.; Makii, H.; Nishinaka, I.; Ota, S. [Advanced Science Research Center, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki 319-1195 (Japan); Nagayama, T. [Advanced Science Research Center, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki 319-1195 (Japan); Graduate School of Science and Engineering, Ibaraki University, Mito 310-0056 (Japan); Tamura, N. [Advanced Science Research Center, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki 319-1195 (Japan); Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan); Goto, S. [Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan); Andreyev, A.N. [Advanced Science Research Center, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki 319-1195 (Japan); Department of Physics, University of York, Heslington, York YO10 5DD (United Kingdom); Vermeulen, M.J. [Advanced Science Research Center, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki 319-1195 (Japan); Gillespie, S.; Barton, C. [Department of Physics, University of York, Heslington, York YO10 5DD (United Kingdom); Kimura, A.; Harada, H. [Nuclear Science and Engineering Center, JAEA, Tokai, Ibaraki 319-1195 (Japan); Meigo, S. [J-PARC Center, JAEA, Tokai, Ibaraki 319-1195 (Japan); Chiba, S. [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Tokyo 152-8550 (Japan); Ohtsuki, T. [Research Reactor Institute, Kyoto University, Kumatori-cho S' ennangun,Osaka 590-0494 (Japan)

2017-06-01

Fission and capture reactions were simultaneously measured in the neutron-induced reactions of {sup 241}Am at the spallation neutron facility of the Japan Proton Accelerator Research Complex (J-PARC). Data for the neutron energy range of E{sub n}=0.1–20 eV were taken with the TOF method. The fission events were observed by detecting prompt neutrons accompanied by fission using liquid organic scintillators. The capture reaction was measured by detecting γ rays emitted in the deexcitation of the compound nuclei using the same detectors, where the prompt fission neutrons and capture γ rays were separated by a pulse shape analysis. The cross sections were obtained by normalizing the relative yields at the first resonance to evaluations or other experimental data. The ratio of the fission to capture cross sections at each resonance is compared with those from an evaluated nuclear data library and other experimental data. Some differences were found between the present values and the library/literature values at several resonances.

Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells

International Nuclear Information System (INIS)

Park, Junghyung; Lee, Dong Gil; Kim, Bokyung; Park, Sun-Ji; Kim, Jung-Hak; Lee, Sang-Rae; Chang, Kyu-Tae; Lee, Hyun-Shik; Lee, Dong-Seok

2015-01-01

Highlights: • FAC-induced iron overload promotes neuronal apoptosis. • Iron overload causes mitochondrial fragmentation in a Drp1-dependent manner. • Iron-induced Drp1 activation depends on dephosphorylation of Drp1(Ser637). • Calcineurin is a key regulator of Drp1-dependent mitochondrial fission by iron. - Abstract: The accumulation of iron in neurons has been proposed to contribute to the pathology of numerous neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. However, insufficient research has been conducted on the precise mechanism underlying iron toxicity in neurons. In this study, we investigated mitochondrial dynamics in hippocampal HT-22 neurons exposed to ferric ammonium citrate (FAC) as a model of iron overload and neurodegeneration. Incubation with 150 μM FAC for 48 h resulted in decreased cell viability and apoptotic death in HT-22 cells. The FAC-induced iron overload triggered mitochondrial fragmentation, which was accompanied by Drp1(Ser637) dephosphorylation. Iron chelation with deferoxamine prevented the FAC-induced mitochondrial fragmentation and apoptotic cell death by inhibiting Drp1(Ser637) dephosphorylation. In addition, a S637D mutation of Drp1, which resulted in a phosphorylation-mimetic form of Drp1 at Ser637, protected against the FAC-induced mitochondrial fragmentation and neuronal apoptosis. FK506 and cyclosporine A, inhibitors of calcineurin activation, determined that calcineurin was associated with the iron-induced changes in mitochondrial morphology and the phosphorylation levels of Drp1. These results indicate that the FAC-induced dephosphorylation of Drp1-dependent mitochondrial fragmentation was rescued by the inhibition of calcineurin activation. Therefore, these findings suggest that calcineurin-mediated phosphorylation of Drp1(Ser637) acts as a key regulator of neuronal cell loss by modulating mitochondrial dynamics in iron-induced toxicity. These results may contribute to the

Deregulation of Mitochondria-Shaping Proteins Opa-1 and Drp-1 in Manganese-Induced Apoptosis

Science.gov (United States)

Alaimo, Agustina; Gorojod, Roxana M.; Beauquis, Juan; Muñoz, Manuel J.; Saravia, Flavia; Kotler, Mónica L.

2014-01-01

Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may

Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.

Directory of Open Access Journals (Sweden)

Agustina Alaimo

Full Text Available Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis

Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.

Science.gov (United States)

Alaimo, Agustina; Gorojod, Roxana M; Beauquis, Juan; Muñoz, Manuel J; Saravia, Flavia; Kotler, Mónica L

2014-01-01

Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may

Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

Science.gov (United States)

Tan, Dun-Xian; Manchester, Lucien C.; Qin, Lilan; Reiter, Russel J.

2016-01-01

Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria. PMID:27999288

Mitochondrial-Shaping Proteins in Cardiac Health and Disease ? the Long and the Short of It!

OpenAIRE

Ong, Sang-Bing; Kalkhoran, Siavash Beikoghli; Hern?ndez-Res?ndiz, Sauri; Samangouei, Parisa; Ong, Sang-Ging; Hausenloy, Derek John

2017-01-01

Mitochondrial health is critically dependent on the ability of mitochondria to undergo changes in mitochondrial morphology, a process which is regulated by mitochondrial shaping proteins. Mitochondria undergo fission to generate fragmented discrete organelles, a process which is mediated by the mitochondrial fission proteins (Drp1, hFIS1, Mff and MiD49/51), and is required for cell division, and to remove damaged mitochondria by mitophagy. Mitochondria undergo fusion to form elongated interco...

Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

Directory of Open Access Journals (Sweden)

Antonio eZorzano

2015-06-01

Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

Measurement of fast neutron induced fission cross section of minor-actinide

International Nuclear Information System (INIS)

Hirakawa, Naohiro

2000-06-01

In fuel cycles with recycled actinide, core characteristics are largely influenced by minor actinide (MA: Np, Am, Cm). Accurate nuclear data of MA such as fission cross section are required to estimate the effect of MA with high accuracy. In this study, fast neutron induced fission cross section of MA is measured using Dynamitron accelerator in Tohoku University. The followings were performed in this fiscal year; (1) Research of nuclear data of MA, (2) Sample preparation and sample mass assay, (3) Investigation of neutron sources with the energy of several 10 keV, (4) Preliminary measurement of fission cross section using Dynamitron accelerator. As the result, four 237 Np samples were prepared and the sample mass were measured using alpha-spectrometry with the accuracy of 1.2%. Then, it was confirmed that a neutron source via 7 Li(p,n) 7 Be reaction using a Li-thick target is suitable for measuring fission cross section of MA in the energy region of several 10 keV. Furthermore, it was verified by the preliminary measurement that the measurement of fission cross section of MA is available using a fission chamber and electronics developed in this study. (author)

Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

International Nuclear Information System (INIS)

Choi, Hong-Seok; Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min; Park, Jeong-Ho; Kim, Jae-Il; Carp, Richard I.; Choi, Eun-Kyoung; Kim, Yong-Sun

2014-01-01

Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

Energy Technology Data Exchange (ETDEWEB)

Choi, Hong-Seok [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Park, Jeong-Ho [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Jae-Il [Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737 (Korea, Republic of); Carp, Richard I. [New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 (United States); Choi, Eun-Kyoung, E-mail: ekchoi@hallym.ac.kr [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Yong-Sun, E-mail: yskim@hallym.ac.kr [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of)

2014-05-30

Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

Prompt muon-induced fission: A probe for nuclear friction in large-amplitude collective motion

International Nuclear Information System (INIS)

Oberacker, V.E.; Umar, A.S.; Wells, J.C.; Strayer, M.R.; Maruhn, J.A.; Reinhard, P.G.

1998-01-01

Excited muonic atoms in the actinide region may induce prompt fission by inverse internal conversion, i.e. the excitation energy of the muonic atom is transferred to the nucleus. The authors solve the time dependent Dirac equation for the muonic spinor wave function in the Coulomb field of the fissioning nucleus on a 3-dimensional lattice and demonstrate that the muon attachment probability to the light fission fragment is a measure of the nuclear energy dissipation between the outer fission barrier and the scission point

Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

Science.gov (United States)

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

2009-02-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer

Study of fission cross sections induced by nucleons and pions using the cascade-exciton model CEM95

International Nuclear Information System (INIS)

Yasin, Z.; Shahzad, M. I.

2007-01-01

Nucleon and pion-induced fission cross sections at intermediate and at higher energies are important in current nuclear applications, such as accelerator driven-systems (ADS), in medicine, for effects on electronics etc. In the present work, microscopic fission cross sections induced by nucleons and pions are calculated using the cascade-exciton model code CEM95 for different projectile-target combinations; at various energies and the computed cross sections are compared with the experimental data found in literature. A new approach is used to compute the fission cross sections in which a change of the ratio of the level density parameter in fission to neutron emission channels was taken into account with the change in the incident energy of the projectile. We are unable to describe well the fission cross sections without using this new approach. Proton induced fission cross sections are calculated for targets 1 97Au, 2 08Pb, 2 09Bi, 2 38U and 2 39Pu in the energy range from 20 MeV to 2000 MeV. Neutron induced fission cross sections are computed for 2 38U and 2 39Pu in the energy range from 20 MeV to 200 MeV. Negative pion induced cross sections for fission are calculated for targets 1 97Au and 2 08Pb from 50 MeV to 2500 MeV energy range. The calculated cross sections are essential to build a data library file for accelerator driven systems just like was built for conventional nuclear reactors. The computed values exhibited reasonable agreement with the experimental values found in the literature across a wide range of beam energies

The Study of Prompt and Delayed Muon Induced Fission. I.Total kinetic energies and mass distributions

NARCIS (Netherlands)

David, P; Hartfiel, J.; Janszen, H.; Petitjean, C.; Reist, H.W.; Polikanov, S.M.; Konijn, J.; Laat, de C.T.A.M.; Taal, A.; Krogulski, T.; Johansson, T.; Tibell, G.; Achard van Enschut, d' J.F.M.

1987-01-01

Mass yield and total kinetic energy release (TKE) distributions of fragments from prompt and delayed muon induced fission, separately, have been measured for the isotopes235U,238U,237Np and242Pu. The distributions from prompt muon induced fission are compared with the corresponding distributions

Heavy ion induced fission between 10 and 100 MeV/u

International Nuclear Information System (INIS)

Steckmeyer, J.C.; Tamain, B.

1986-05-01

Heavy ion induced fission between 10 and 100 MeV/u is discussed. It is shown that one can obtain information on fusion limits and on typical times characterizing nuclear matter. Intermediate energy heavy ions can be used to build very excited fusion nuclei. Section I shows that fission can then be used as a tool to test the fusion mechanism and to discover what are the extreme limits concerning fusion and hot nuclei formation. In section II, it is shown that when very hot nuclei are built, fission evaporation competition cannot any longer be fully described in the usual way by the statistical model. New features as dynamical aspects or cluster evaporation modify dramatically the landscape. Concerning the detailed fission properties of very hot nuclei (for instance fragments properties), no strong deviations from the already know systematics has been obtained. However, very few detailed studies are yet available and a clear experimental program has to be developed in order to progress. From a theoretical point of view, it is rather necessary to described fission and evaporation is an unified way

Manifestation of transient effects in fission induced by relativistic heavy-ion collisions

Energy Technology Data Exchange (ETDEWEB)

Jurado, B.; Schmitt, C.; Schmidt, K.H.; Benlliure, J. [Universidad de Santiago de Compostela (Spain); Junghans, A.R. [Forschungszentrum Rossendorf e.V. (FZR), Dresden (Germany)

2004-03-01

We examine the manifestation of transient effects in fission by analysing experimental data where fission is induced by peripheral heavy-ion collisions at relativistic energies. Available total nuclear fission cross sections of {sup 238}U at1.A GeV on gold and uranium targets are compared with a nuclear-reaction code, where transient effects in fission are modelled using different approximations to the numerical time-dependent fission-decay width: a new analytical description based on the solution of the Fokker-Planck equation and two widely used but less realistic descriptions, a step function and an exponential-like function. The experimental data are only reproduced when transient effects are considered. The deduced value of the dissipation strength {beta} depends strongly on the approximation applied for the time-dependent fission-decay width and is estimated to be of the order of 2 x 10{sup 21} s{sup -1}. A careful analysis sheds severe doubts on the use of the exponential-like in-growth function largely used in the past. Finally, we discuss which should be the characteristics of experimental observables to be most sensitive to transient effects in fission. (orig.)

Monte Carlo simulation of fission yields, kinetic energy, fission neutron spectrum and decay γ-ray spectrum for 232Th(n,f) reaction induced by 3H(d,n) 4He neutron source

International Nuclear Information System (INIS)

Zheng Wei; Zeen Yao; Changlin Lan; Yan Yan; Yunjian Shi; Siqi Yan; Jie Wang; Junrun Wang; Jingen Chen; Chinese Academy of Sciences, Shanghai

2015-01-01

Monte Carlo transport code Geant4 has been successfully utilised to study of neutron-induced fission reaction for 232 Th in the transport neutrons generated from 3 H(d,n) 4 He neutron source. The purpose of this work is to examine the applicability of Monte Carlo simulations for the computation of fission reaction process. For this, Monte Carlo simulates and calculates the characteristics of fission reaction process of 232 Th(n,f), such as the fission yields distribution, kinetic energy distribution, fission neutron spectrum and decay γ-ray spectrum. This is the first time to simulate the process of neutron-induced fission reaction using Geant4 code. Typical computational results of neutron-induced fission reaction of 232 Th(n,f) reaction are presented. The computational results are compared with the previous experimental data and evaluated nuclear data to confirm the certain physical process model in Geant4 of scientific rationality. (author)

Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis.

Science.gov (United States)

Renault, Thibaud T; Floros, Konstantinos V; Elkholi, Rana; Corrigan, Kelly-Ann; Kushnareva, Yulia; Wieder, Shira Y; Lindtner, Claudia; Serasinghe, Madhavika N; Asciolla, James J; Buettner, Christoph; Newmeyer, Donald D; Chipuk, Jerry E

2015-01-08

Proapoptotic BCL-2 proteins converge upon the outer mitochondrial membrane (OMM) to promote mitochondrial outer membrane permeabilization (MOMP) and apoptosis. Here we investigated the mechanistic relationship between mitochondrial shape and MOMP and provide evidence that BAX requires a distinct mitochondrial size to induce MOMP. We utilized the terminal unfolded protein response pathway to systematically define proapoptotic BCL-2 protein composition after stress and then directly interrogated their requirement for a productive mitochondrial size. Complementary biochemical, cellular, in vivo, and ex vivo studies reveal that Mfn1, a GTPase involved in mitochondrial fusion, establishes a mitochondrial size that is permissive for proapoptotic BCL-2 family function. Cells with hyperfragmented mitochondria, along with size-restricted OMM model systems, fail to support BAX-dependent membrane association and permeabilization due to an inability to stabilize BAXα9·membrane interactions. This work identifies a mechanistic contribution of mitochondrial size in dictating BAX activation, MOMP, and apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.

The study of prompt neutron spectra of 238U fission induced by fast neutron

International Nuclear Information System (INIS)

Li Anli; Bai Xixiang; Wang Yufeng; Wang Xiaozhong; Men Jiangchen; Huang Shengnian

1990-01-01

The measurements of prompt neutron time-of-flight spectra of U fission induced by 11 MeV neutrons were carried out at HI-13 Tandem Van de Graaff Accelerator Laboratory in 1989. The block diagram of the electronics is shown. A fission neutron TOF spectrum for the sixth section of the fission plates and the left detector at low bias is given. The data accumulation time is 60 h

Mitochondrial rejuvenation after induced pluripotency.

Directory of Open Access Journals (Sweden)

Steven T Suhr

2010-11-01

Full Text Available As stem cells of the early embryo mature and differentiate into all tissues, the mitochondrial complement undergoes dramatic functional improvement. Mitochondrial activity is low to minimize generation of DNA-damaging reactive oxygen species during pre-implantation development and increases following implantation and differentiation to meet higher metabolic demands. It has recently been reported that when the stem cell type known as induced pluripotent stem cells (IPSCs are re-differentiated for several weeks in vitro, the mitochondrial complement progressively re-acquires properties approximating input fibroblasts, suggesting that despite the observation that IPSC conversion "resets" some parameters of cellular aging such as telomere length, it may have little impact on other age-affected cellular systems such as mitochondria in IPSC-derived cells.We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1 that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2 the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal.These results - coupled with earlier data from our laboratory - suggest that IPSC conversion not only resets the "biological clock", but can also rejuvenate the energetic capacity of derived cells.

Proton induced fission of {sup 232}Th at intermediate energies

Energy Technology Data Exchange (ETDEWEB)

Gikal, K. B., E-mail: kgikal@mail.ru; Kozulin, E. M.; Bogachev, A. A. [JINR, Flerov Laboratory of Nuclear Reactions (Russian Federation); Burtebaev, N. T.; Edomskiy, A. V. [Institute of Nuclear Physics of Ministry of Energy of the Republic of Kazakhstan (Kazakhstan); Itkis, I. M.; Itkis, M. G.; Knyazhev, G. N. [JINR, Flerov Laboratory of Nuclear Reactions (Russian Federation); Kovalchuk, K. V.; Kvochkina, T. N. [Institute of Nuclear Physics of Ministry of Energy of the Republic of Kazakhstan (Kazakhstan); Piasecki, E. [Heavy Ion Laboratory of Warsaw University (Poland); Rubchenya, V. A. [University of Jyväskylä, Department of Physics (Finland); Sahiev, S. K. [Institute of Nuclear Physics of Ministry of Energy of the Republic of Kazakhstan (Kazakhstan); Trzaska, W. H. [University of Jyväskylä, Department of Physics (Finland); Vardaci, E. [INFN Napoli, Dipartimento di Scienze Fisiche dell’Università di Napoli (Italy)

2016-12-15

The mass-energy distributions and cross sections of proton-induced fission of {sup 232}Th have been measured at the proton energies of 7, 10, 13, 20, 40, and 55 MeV. Experiments were carried out at the proton beam of the K-130 cyclotron of the JYFL Accelerator Laboratory of the University of Jyväskylä and U-150m cyclotron of the Institute of Nuclear Physics, Ministry of Energy of the Republic of Kazakhstan. The yields of fission fragments in the mass range A = 60–170 a.m.u. have been measured up to the level of 10−4%. The three humped shape of the mass distribution up has been observed at higher proton energies. The contribution of the symmetric component grows up with increasing proton incident energy; although even at 55 MeV of proton energy the shoulders in the mass energy distribution clearly indicate the asymmetric fission peaks. Evolution of shell structure was observed in the fission fragment mass distributions even at high excitation energy.

Unified description of neutron-, proton- and photon-induced fission cross sections in intermediate energy region

International Nuclear Information System (INIS)

Fukahori, Tokio; Iwamoto, Osamu; Chiba, Satoshi

2003-01-01

For an accelerator-driven nuclear waste transmutation system, it is very important to estimate sub-criticality of core system for feasibility and design study of the system. The fission cross section in the intermediate energy range has an important role. A program FISCAL has been developed to calculate neutron-, proton- and photon-induced fission cross sections in the energy region from several tens of MeV to 3 GeV. FISCAL adopts the systematics considering experimental data for Ag- 243 Am. It is found that unified description of neutron-, proton- and photon-induced fission cross sections is available. (author)

Salvianolic Acid-A Induces Apoptosis, Mitochondrial Membrane ...

African Journals Online (AJOL)

using Hoechst 33258 staining. The effect of the compound on mitochondrial membrane potential loss ... Fluorescence microscopy demonstrated that salvianolic acid-A induced dose- dependent ..... aggregation and anticancer properties. It has.

Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

Energy Technology Data Exchange (ETDEWEB)

Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček, Tomáš; Pajuelo Reguera, David; Jabůrek, Martin; Ježek, Petr

2016-07-01

Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM

Measurement of fast neutron induced fission cross section of minor-actinide

International Nuclear Information System (INIS)

Hirakawa, Naohiro

1997-03-01

In fuel cycles with recycled actinide, core characteristics are largely influenced by minor actinide (MA: Np, Am, Cm). Accurate nuclear data of MA such as fission cross section are required to estimate the effect of MA with high accuracy. In this study, fast neutron induced fission cross section of MA is measured using Dynamitron Accelerator in Tohoku University. The experimental method and the samples, which were developed or introduced during the last year, were improved in this fiscal year: (1) Development of a sealed fission chamber, (2) Intensification of Li neutron target, (3) Improvement of time-resolution of Time-of-Flight (TOF) electronic circuit, (4) Introduction of Np237 samples with large sample mass and (5) Introduction of a U235 sample with high purity. Using these improved tools and samples, the fission cross section ratio of Np237 relative to U235 was measured between 5 to 100 keV, and the fission cross section of Np237 was deduced. On the other hand, samples of Am241 and Am243 were obtained from Japan Atomic Energy Research Institute (JAERI) after investigating fission cross section of two americium isotopes (Am241 and Am 243) which are important for core physics calculation of fast reactors. (author)

MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress

Directory of Open Access Journals (Sweden)

Neeharika Nemani

2018-04-01

Full Text Available Summary: Mitochondria shape cytosolic calcium ([Ca2+]c transients and utilize the mitochondrial Ca2+ ([Ca2+]m in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+-induced shape change that is distinct from mitochondrial fission and swelling. [Ca2+]c elevation, but not MCU-mediated Ca2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST. MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca2+-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca2+ sensor that decodes metazoan Ca2+ signals as MiST. : Metazoan Ca2+ signal determines mitochondrial shape transition (MiST and cellular quality control. Nemani et al. find that mitochondria undergo shape changes upon Ca2+ stress. MiST is distinct from matrix Ca2+-induced swelling and mitochondrial dynamics. The conserved Ca2+ sensor Miro1 enables MiST and promotes autophagy/mitophagy. Keywords: mitochondrial shape, MiST, calcium, Miro, EF hand, PTP, MCU, mitophagy, autophagy, mitochondrial dynamics

Charged particle-induced nuclear fission reactions

Indian Academy of Sciences (India)

The nuclear fission phenomenon continues to be an enigma, even after nearly 75 years of its discovery. Considerable progress has been made towards understanding the fission process. Both light projectiles and heavy ions have been employed to investigate nuclear fission. An extensive database of the properties of ...

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

Directory of Open Access Journals (Sweden)

Jung Hyun Park

2017-01-01

Full Text Available Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2 regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA- transfected Lewis lung carcinoma (LLC cells and idh2-deficient (idh2−/− mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2−/− mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration.

Science.gov (United States)

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP + -dependent isocitrate dehydrogenase ( idh2 ) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2 -deficient ( idh2 -/- ) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2 -/- mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

Development of prototype induced-fission-based Pu accountancy instrument for safeguards applications.

Science.gov (United States)

Seo, Hee; Lee, Seung Kyu; An, Su Jung; Park, Se-Hwan; Ku, Jeong-Hoe; Menlove, Howard O; Rael, Carlos D; LaFleur, Adrienne M; Browne, Michael C

2016-09-01

Prototype safeguards instrument for nuclear material accountancy (NMA) of uranium/transuranic (U/TRU) products that could be produced in a future advanced PWR fuel processing facility has been developed and characterized. This is a new, hybrid neutron measurement system based on fast neutron energy multiplication (FNEM) and passive neutron albedo reactivity (PNAR) methods. The FNEM method is sensitive to the induced fission rate by fast neutrons, while the PNAR method is sensitive to the induced fission rate by thermal neutrons in the sample to be measured. The induced fission rate is proportional to the total amount of fissile material, especially plutonium (Pu), in the U/TRU product; hence, the Pu amount can be calibrated as a function of the induced fission rate, which can be measured using either the FNEM or PNAR method. In the present study, the prototype system was built using six (3)He tubes, and its performance was evaluated for various detector parameters including high-voltage (HV) plateau, efficiency profiles, dead time, and stability. The system's capability to measure the difference in the average neutron energy for the FNEM signature also was evaluated, using AmLi, PuBe, (252)Cf, as well as four Pu-oxide sources each with a different impurity (Al, F, Mg, and B) and producing (α,n) neutrons with different average energies. Future work will measure the hybrid signature (i.e., FNEM×PNAR) for a Pu source with an external interrogating neutron source after enlarging the cavity size of the prototype system to accommodate a large-size Pu source (~600g Pu). Copyright © 2016 Elsevier Ltd. All rights reserved.

Fast-neutron-induced fission of 242Pu at nELBE

Directory of Open Access Journals (Sweden)

Kögler Toni

2017-01-01

Full Text Available The fast neutron-induced fission cross section of 242Pu was determined in the range of 0.5 MeV to 10 MeV relative to 235U(n,f at the neutron time-of-flight facility nELBE. The number of target nuclei was calculated by means of measuring the spontaneous fission rate of 242Pu. Neutron transport simulations with Geant4 and MCNP6 are used to correct the relative cross section for neutron scattering. The determined results are in good agreement with current experimental and evaluated data sets.

Fission neutron multiplicity calculations

International Nuclear Information System (INIS)

Maerten, H.; Ruben, A.; Seeliger, D.

1991-01-01

A model for calculating neutron multiplicities in nuclear fission is presented. It is based on the solution of the energy partition problem as function of mass asymmetry within a phenomenological approach including temperature-dependent microscopic energies. Nuclear structure effects on fragment de-excitation, which influence neutron multiplicities, are discussed. Temperature effects on microscopic energy play an important role in induced fission reactions. Calculated results are presented for various fission reactions induced by neutrons. Data cover the incident energy range 0-20 MeV, i.e. multiple chance fission is considered. (author). 28 refs, 13 figs

Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons.

Science.gov (United States)

Qu, Mingyue; Jiang, Zheng; Liao, Yuanxiang; Song, Zhenyao; Nan, Xinzhong

2016-06-01

Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

Induced fission of nuclei: dynamical chaos and lifetime of compound nucleus

Energy Technology Data Exchange (ETDEWEB)

Krivoshej, I V

1987-01-01

A semi-phenomenological theory is proposed to describe the induced fission of heavy nuclei at low and intermediate excitation energies. The theory is based on the concept of the dynamical chaos, arising because of a negative curvature of the n-dimensional potential energy surface (PES). The nuclear fission is treated as a diffusion of the representing point across a vicinity of the saddle point in PES. The diffusion coefficient is calculated for various metrics in PES as an explicit function of the two-dimensional curvatures at the saddle point of PES. The present theory suggests an estimate for the fission time, tau/sub f/approx.10/sup -14/ s. Coefficients of nuclear friction and viscosity are also calculated in general, and the resulting numerical estimates are in agreement with the experimental data.

Neutron kinetics in moderators and SNM detection through epithermal-neutron-induced fissions

Energy Technology Data Exchange (ETDEWEB)

Gozani, Tsahi, E-mail: tgmaven@gmail.com [1050 Harriet St., Palo Alto, CA 94301 (United States); King, Michael J. [Rapiscan Laboratories Inc., 520 Almanor Ave., Sunnyvale, CA 94085 (United States)

2016-01-01

Extension of the well-established Differential Die Away Analysis (DDAA) into a faster time domain, where more penetrating epithermal neutrons induce fissions, is proposed and demonstrated via simulations and experiments. In the proposed method the fissions stimulated by thermal, epithermal and even higher-energy neutrons are measured after injection of a narrow pulse of high-energy 14 MeV (d,T) or 2.5 MeV (d,D) source neutrons, appropriately moderated. The ability to measure these fissions stems from the inherent correlation of neutron energy and time (“E–T” correlation) during the process of slowing down of high-energy source neutrons in common moderating materials such as hydrogenous compounds (e.g., polyethylene), heavy water, beryllium and graphite. The kinetic behavior following injection of a delta-function-shaped pulse (in time) of 14 MeV neutrons into such moderators is studied employing MCNPX simulations and, when applicable, some simple “one-group” models. These calculations served as a guide for the design of a source moderator which was used in experiments. Qualitative relationships between slowing-down time after the pulse and the prevailing neutron energy are discussed. A laboratory system consisting of a 14 MeV neutron generator, a polyethylene-reflected Be moderator, a liquid scintillator with pulse-shape discrimination (PSD) and a two-parameter E–T data acquisition system was set up to measure prompt neutron and delayed gamma-ray fission signatures in a 19.5% enriched LEU sample. The measured time behavior of thermal and epithermal neutron fission signals agreed well with the detailed simulations. The laboratory system can readily be redesigned and deployed as a mobile inspection system for SNM in, e.g., cars and vans. A strong pulsed neutron generator with narrow pulse (<75 ns) at a reasonably high pulse frequency could make the high-energy neutron induced fission modality a realizable SNM detection technique.

Nuclear fission and reactions

International Nuclear Information System (INIS)

Anon.

1975-01-01

The nuclear fission research programs are designed to elucidate basic features of the fission process. Specifically, (1) factors determining how nucleons of a fissioning nucleus are distributed between two fission fragments, (2) factors determining kinetic energy and excitation energies of fragments, and (3) factors controlling fission lifetimes. To these ends, fission studies are reported for several heavy elements and include investigations of spontaneous and neutron-induced fission, heavy ion reactions, and high energy proton reactions. The status of theoretical research is also discussed. (U.S.)

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.

Science.gov (United States)

Taghizadeh, Ghorban; Pourahmad, Jalal; Mehdizadeh, Hajar; Foroumadi, Alireza; Torkaman-Boutorabi, Anahita; Hassani, Shokoufeh; Naserzadeh, Parvaneh; Shariatmadari, Reyhaneh; Gholami, Mahdi; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2016-10-01

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function. Copyright © 2016 Elsevier Inc. All rights reserved.

The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

Energy Technology Data Exchange (ETDEWEB)

Liu, Tong; Yu, Rong [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Jin, Shao-Bo [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Han, Liwei [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Lendahl, Urban [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Zhao, Jian, E-mail: Jian.Zhao@ki.se [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Nistér, Monica [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden)

2013-11-01

Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

International Nuclear Information System (INIS)

Liu, Tong; Yu, Rong; Jin, Shao-Bo; Han, Liwei; Lendahl, Urban; Zhao, Jian; Nistér, Monica

2013-01-01

Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

Analytic computation of average energy of neutrons inducing fission

International Nuclear Information System (INIS)

Clark, Alexander Rich

2016-01-01

The objective of this report is to describe how I analytically computed the average energy of neutrons that induce fission in the bare BeRP ball. The motivation of this report is to resolve a discrepancy between the average energy computed via the FMULT and F4/FM cards in MCNP6 by comparison to the analytic results.

The importance of the giant resonances in hadron and muon induced fission

International Nuclear Information System (INIS)

Hartfiel, J.

1985-01-01

In the first part of the thesis the fission probability of 238 U by means of the reaction 238 U(α,α'f) is studied at an incident energy of 480 MeV and a scattering angle of 3.4 0 . In the measured spectrum of the inelastically scattered α particles a strong resonance is found in the excitation energy range from 8 to 13 MeV. The center of mass of the resonance lies at 11 MeV. Its width extends to 4.5 MeV. In the second part of the thesis the muon induced fission of 235 U, 238 U, 237 Np, 242 Pu, and 244 Pu is studied. Thereby both fission fragments are detected in coincidence by two surface barrier detectors. By this it is possible for the first time to measure the mass and kinetic energy distribution of the fission fragments. (orig./HSI) [de

Fission studies of gold induced by (1665 MeV) π- using a CR-39 detector

International Nuclear Information System (INIS)

Muhammad Ikram Shahzad; Yasin, Zafar; Sher, Gul

2012-01-01

The fission cross section and fission probability of 197 Au, induced by (1665 MeV) π'-, have been studied using CR-39 track detectors. A 4π-geometry was used to count track statistics. A beam of negative pions of 1665 MeV was produced at AGS of Brookhaven National Laboratory, USA, and allowed to fall normally on the stack. Two detectors from the stack were scanned for fission fragment tracks after etching in 6N NaOH at 70 ℃. The statistics of fission fragment tracks in both detectors were obtained. It was found that there was a marked asymmetry of registered tracks with respect to the forward and backward hemispheres. This asymmetry could be partly accounted for on the basis of momentum transfer to the struck nucleus. On the basis of counting statistics fission cross section was measured, and fission probability was determined by dividing the fission cross section with the reaction cross section. The fission cross-section and fission probability were compared with the computed values using the cascade-exciton model code CEM95. (authors)

Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions

Science.gov (United States)

Marullo, Rossella; Werner, Erica; Degtyareva, Natalya; Moore, Bryn; Altavilla, Giuseppe; Ramalingam, Suresh S.; Doetsch, Paul W.

2013-01-01

Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy. PMID:24260552

Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Kanae Iijima-Ando

2009-12-01

Full Text Available The amyloid-beta 42 (Abeta42 is thought to play a central role in the pathogenesis of Alzheimer's disease (AD. However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Abeta42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Abeta42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Abeta42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Abeta42 in vivo.

An IPTG-inducible derivative of the fission yeast nmt promoter

DEFF Research Database (Denmark)

Kjærulff, Søren; Nielsen, Olaf

2015-01-01

We here describe an IPTG-inducible system that reveals that the lac repressor alone can function as a potent transmodulator to regulate gene expression in the fission yeast, Schizosaccharomyces pombe. This expression system is a derivative of the Sz. pombe nmt promoter, which normally is strongly...

Effects of fissioning nuclei distributions on fragment mass distributions for high energy fission

Directory of Open Access Journals (Sweden)

Rossi P C R

2012-02-01

Full Text Available We study the effects of fissioning nuclei mass- and energy-distributions on the formation of fragments for fission induced by high energy probes. A Monte Carlo code called CRISP was used for obtaining mass distributions and spectra of the fissioning nuclei for reactions induced by 660 MeV protons on 241Am and on 239Np, by 500 MeV protons on 208Pb, and by Bremsstrahlung photons with end-point energies at 50 MeV and 3500 MeV on 238U. The results show that even at high excitation energies, asymmetric fission may still contribute significantly to the fission cross section of actinide nuclei, while it is the dominante mode in the case of lead. However, more precise data for high energy fission on actinide are necessary in order to allow definite conclusions.

New signatures on dissipation from fission induced by relativistic heavy-ion collisions

Energy Technology Data Exchange (ETDEWEB)

Jurado, B.; Schmitt, C.; Schmidt, K.H.; Enqvist, T.; Kelic, A.; Rejmund, F.; Benlliure, J. [Universidad de Santiago de Compostela (Spain); Junghans, A.R. [Forschungszentrum Rossendorf e.V. (FZR), Dresden (Germany)

2004-03-01

Fissile nuclei with small shape distortion relative to the ground-state deformation and with low angular momentum were produced in peripheral heavy-ion collisions. Under the conditions of small shape distortions and low angular momentum, the theoretical description of the fission process can be considerably simplified, and the relevant information on dissipation can be better extracted than in conventional experiments based on fusion-fission reactions. In addition, this experimental approach induces very high excitation energies, a condition necessary to observe transient effects. The experimental data were taken at GSI using a set-up especially conceived for fission studies in inverse kinematics. This set-up allowed determining three observables whose sensitivity to dissipation was investigated for the first time: the total fission cross sections of {sup 238}U at 1 A GeV as a function of the target mass, and, for the reaction of {sup 238}U at 1 A GeV on a (CH{sub 2}){sub n} target, the partial fission cross sections and the partial charge distributions of the fission fragments. The comparison of the new experimental data with a reaction code adapted to the conditions of the reactions investigated leads to clear conclusions on the strength of dissipation at small deformation where the existing results are rather contradictory. (orig.)

New signatures on dissipation from fission induced by relativistic heavy-ion collisions

International Nuclear Information System (INIS)

Jurado, B.; Schmitt, C.; Schmidt, K.H.; Enqvist, T.; Kelic, A.; Rejmund, F.; Benlliure, J.; Junghans, A.R.

2004-03-01

Fissile nuclei with small shape distortion relative to the ground-state deformation and with low angular momentum were produced in peripheral heavy-ion collisions. Under the conditions of small shape distortions and low angular momentum, the theoretical description of the fission process can be considerably simplified, and the relevant information on dissipation can be better extracted than in conventional experiments based on fusion-fission reactions. In addition, this experimental approach induces very high excitation energies, a condition necessary to observe transient effects. The experimental data were taken at GSI using a set-up especially conceived for fission studies in inverse kinematics. This set-up allowed determining three observables whose sensitivity to dissipation was investigated for the first time: the total fission cross sections of 238 U at 1 A GeV as a function of the target mass, and, for the reaction of 238 U at 1 A GeV on a (CH 2 ) n target, the partial fission cross sections and the partial charge distributions of the fission fragments. The comparison of the new experimental data with a reaction code adapted to the conditions of the reactions investigated leads to clear conclusions on the strength of dissipation at small deformation where the existing results are rather contradictory. (orig.)

Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

International Nuclear Information System (INIS)

Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

2010-01-01

The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt max of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

Coulomb fission and transfer fission at heavy ion collisions

International Nuclear Information System (INIS)

Himmele, G.

1981-01-01

In the present thesis the first direct evidence of nuclear fission after inelastic scattering of heavy ions (sup(183,184)W, 152 Sm → 238 U; 184 W → 232 Th; 184 W, 232 Th → 248 Cm) is reported. Experiments which were performed at the UNILAC of the Gesellschaft fuer Schwerionenforschung in Darmstadt show the observed heavy ion induced fission possesses significant properties of the Coulomb fission. The observed dependence of the fission probability for inelastic scattering on the projectile charge proves that the nuclear fission is mediated by the electromagnetic interaction between heavy ions. This result suggests moreover a multiple Coulomb-excitation preceding the fission. Model calculations give a first indication, that the Coulomb fission proceeds mainly from the higher β phonons. In the irradiation with 184 W the fission probability of 232 Th is for all incident energies about 40% smaller that at 238 U. The target dependence of the Coulomb fission however doesn't allow, to give quantitative statements about the position and B(E2)-values of higher lying β phonons. (orig./HSI) [de

Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

Science.gov (United States)

Diao, Lei; Mei, Qiao; Xu, Jian-Ming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Mo-Li

2012-03-14

To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

Binary and ternary fission yields induced by 12C and 20Ne ions on 238U targets

International Nuclear Information System (INIS)

Otto, R.J.

1974-01-01

Evidence for ternary fission of 250 Cf* and 258 No* compound nuclei has been found. Relative cross section data for nuclides with masses between 24 Na and 161 Tb have been determined for 12 C bombardments of natural uranium at laboratory energies of 122 MeV, 113 MeV and 105 MeV. Relative cross section data for 8 nuclides between 24 Na and 66 Ni were sought for 20 Ne bombardments of natural uranium at 150 MeV laboratory energies. The binary fission fragment mass distribution for 238 U( 12 C,f) was determined by analysis of fission fragment recoil collection foils using radiochemical techniques and high resolution gamma ray spectroscopy. The results indicated the existence of a ternary fission branch similar to mass distributions obtained for He induced fission of Th, U, and Pu nuclei at intermediate energies. Comparison of the data with He induced ternary fission data obtained previously in this laboratory indicated an increase in the ternary fission probability with increasing Z 2 /A of the compound nucleus and with excitation energy. A shift of the binary-ternary fission product intersection point to lower mass numbers with increasing Z 2 /A and excitation energy of the compound nucleus was also observed. (Diss. Abstr. Int., B)

Relativistic Coulomb Fission

Science.gov (United States)

Norbury, John W.

1992-01-01

Nuclear fission reactions induced by the electromagnetic field of relativistic nuclei are studied for energies relevant to present and future relativistic heavy ion accelerators. Cross sections are calculated for U-238 and Pu-239 fission induced by C-12, Si-28, Au-197, and U-238 projectiles. It is found that some of the cross sections can exceed 10 b.

Measurements of isomeric yield ratios of fission products from proton-induced fission on natU and 232Th via direct ion counting

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Rakopoulos Vasileios

2017-01-01

Full Text Available Independent isomeric yield ratios (IYR of 81Ge, 96Y, 97Y, 97Nb, 128Sn and 130Sn have been determined in the 25 MeV proton-induced fission of natU and 232Th. The measurements were performed at the Ion Guide Isotope Separator On-Line (IGISOL facility at the University of Jyväskylä. A direct ion counting measurement of the isomeric fission yield ratios was accomplished for the first time, registering the fission products in less than a second after their production. In addition, the IYRs of natU were measured by means of γ-spectroscopy in order to verify the consistency of the recently upgraded experimental setup. From the obtained results, indications of a dependence of the production rate on the fissioning system can be noticed. These data were compared with data available in the literature, whenever possible. Using the TALYS code and the experimentally obtained IYRs, we also deduced the average angular momentum of the fission fragments after scission.

Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

International Nuclear Information System (INIS)

Perez-de-Arce, Karen; Foncea, Rocio; Leighton, Federico

2005-01-01

It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-κB activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy

PREVENTION OF PHOSPHATE - INDUCED MITOCHONDRIAL SWELLING

Science.gov (United States)

Kroll, Arnold J.; Kuwabara, Toichiro

1962-01-01

The prevention of phosphate-induced mitochondrial swelling in the whole retina of the rabbit was studied with the electron microscope. It was found that a mixture of ATP, Mg++, and bovine serum albumin protected the mitochondria in vitro. This finding confirmed the results obtained spectrophotometrically with isolated rat liver mitochondria by Lehninger. PMID:13927020

Angular distribution of fragments from neutron-induced fission of 238U in the intermediate energy region

International Nuclear Information System (INIS)

Carlsson, Magnus

2004-06-01

Areas ranging from nuclear structure models to accelerator-driven systems benefit from improved neutron-induced fission data in the intermediate energy region. In this Master's degree thesis, the fragment angular distribution from fission of 238 U, induced by 21-MeV neutrons, has been analysed from an experiment performed with the Medley/DIFFICILE setup at the The Svedberg Laboratory in Uppsala. The data have been corrected for low energy neutrons in the beam. The results agree with other experiments, as well as with model calculations. The data should be a starting point for further analysis with a goal to deduce the fission cross-section of 238 U

Mass dependence of positive pion-induced fission

International Nuclear Information System (INIS)

Khan, H.A.; Khan, N.A.; Peterson, R.J.

1991-01-01

Fission cross sections for a range of targets have been measured by solid-state track detectors following 80 and 100 MeV π + bombardment. Fission probabilities have been inferred by comparison to computed reaction cross sections. Fission probabilities for heavy targets agree with those for other probes of comparable energy and with statistical calculations. Probabilities for lighter targets are much above those previously observed or computed. Ternary fission cross sections and multiplicities of light fragments have also been determined

Mitochondrial cristae remodelling is associated with disrupted OPA1 oligomerisation in the Huntington's disease R6/2 fragment model.

Science.gov (United States)

Hering, Tanja; Kojer, Kerstin; Birth, Nathalie; Hallitsch, Jaqueline; Taanman, Jan-Willem; Orth, Michael

2017-02-01

There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals. Mitochondrial morphology was determined using electron microscopy, and transcript and protein levels of factors that play a key role in fission and fusion, including DRP1, mitofusin 1 and 2, mitofilin and OPA1, and cytochrome c and caspase 3 were assessed by RT-qPCR and immunoblotting. OPA1 oligomerisation was evaluated using blue native gels. In striatum and cortex of R6/2 mice, mitochondrial cristae morphology was abnormal. Mitofilin and the overall levels of the fission and fusion factors were unaffected; however, OPA1 oligomerisation was abnormal in striatum and cortex of R6/2 mice. Mitochondrial and cytoplasmic cytochrome c levels were similar in R6/2 and wild-type mice with no significant increase of activated caspase 3. Our results indicate that the integrity of the mitochondrial cristae is compromised in striatum and cortex of the R6/2 mice and that this is most likely caused by impaired OPA1 oligomerisation. Copyright © 2016 Elsevier Inc. All rights reserved.

Neutron emission as a probe of fusion-fission and quasi-fission dynamics

International Nuclear Information System (INIS)

Hinde, D.J.

1991-01-01

Pre- and post scission neutron yeilds have been measured as a function of projectile mass, compound nucleus fissility, and fission mass-split and total kinetic energy (TKE) for 27 fusion-fission and quasi-fission reactions induced by beams of 16,18 O, 40 Ar and 64 Ni. A new method of interpretation of experimental pre-scission neutron multiplicities ν-pre and mean kinetic energies ε ν allows the extraction of fission time scales with much less uncertainty than previously, all fusion-fission results being consistent with a dynamical time scale of (35±15) x 10 -21 s for symmetric fission. All reactions show that ν-pre falls quite rapidly with increasing mass-asymmetry; evidence is presented that for fusion-fission reactions this is partly due to a reduction of the dynamical fission time scale with mass-asymmetry. For quasi-fission, the data indicate that the pre-scission multiplicity and mean neutron kinetic energy are very sensitive to the final mass-asymmetry, but that the time scale is virtually independent of mass-asymmetry. It is concluded that for fusion-fission there is no dependence of ν-pre on TKE, whilst for 64 Ni-induced quasi-fission reactions, a strong increase of ν-pre with decreasing TKE is observed, probably largely caused by neutron emission during the acceleration time of the fission fragments in these fast reactions. Interpretation of post-scission multiplicities in terms of fragment excitation energies leads to deduced time scales consistent with those determined from the pre-scission data. 54 refs., 17 tabs., 25 figs

Investigation of the heavy nuclei fission with anomalously high values of the fission fragments total kinetic energy

Science.gov (United States)

Khryachkov, Vitaly; Goverdovskii, Andrei; Ketlerov, Vladimir; Mitrofanov, Vecheslav; Sergachev, Alexei

2018-03-01

Binary fission of 232Th and 238U induced by fast neutrons were under intent investigation in the IPPE during recent years. These measurements were performed with a twin ionization chamber with Frisch grids. Signals from the detector were digitized for further processing with a specially developed software. It results in information of kinetic energies, masses, directions and Bragg curves of registered fission fragments. Total statistics of a few million fission events were collected during each experiment. It was discovered that for several combinations of fission fragment masses their total kinetic energy was very close to total free energy of the fissioning system. The probability of such fission events for the fast neutron induced fission was found to be much higher than for spontaneous fission of 252Cf and thermal neutron induced fission of 235U. For experiments with 238U target the energy of incident neutrons were 5 MeV and 6.5 MeV. Close analysis of dependence of fission fragment distribution on compound nucleus excitation energy gave us some explanation of the phenomenon. It could be a process in highly excited compound nucleus which leads the fissioning system from the scission point into the fusion valley with high probability.

Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium.

Science.gov (United States)

Kamdar, O; Le, Wei; Zhang, J; Ghio, A J; Rosen, G D; Upadhyay, D

2008-10-29

We studied the effects of airborne particulate matters (PM) on cystic fibrosis (CF) epithelium. We noted that PM enhanced human CF bronchial epithelial apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane potential. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic acid, rotenone and thenoyltrifluoroacetone) blocked PM-induced generation of reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53 and p21; and enhanced mitochondrial localization of Bax. The anti-apoptotic Bcl-2, Bcl-xl, Mcl-1 and Xiap remained unchanged; however, overexpression of Bcl-xl blocked PM-induced apoptosis. Accordingly, we provide the evidence that PM enhances oxidative stress and mitochondrial signaling mediated apoptosis via the modulation of Bcl family proteins in CF.

The dual role of cyclin C connects stress regulated gene expression to mitochondrial dynamics

Directory of Open Access Journals (Sweden)

Randy Strich

2014-09-01

Full Text Available Following exposure to cytotoxic agents, cellular damage is first recognized by a variety of sensor mechanisms. Thenceforth, the damage signal is transduced to the nucleus to install the correct gene expression program including the induction of genes whose products either detoxify destructive compounds or repair the damage they cause. Next, the stress signal is disseminated throughout the cell to effect the appropriate changes at organelles including the mitochondria. The mitochondria represent an important signaling platform for the stress response. An initial stress response of the mitochondria is extensive fragmentation. If the damage is prodigious, the mitochondria fragment (fission and lose their outer membrane integrity leading to the release of pro-apoptotic factors necessary for programmed cell death (PCD execution. As this complex biological process contains many moving parts, it must be exquisitely coordinated as the ultimate decision is life or death. The conserved C-type cyclin plays an important role in executing this molecular Rubicon by coupling changes in gene expression to mitochondrial fission and PCD. Cyclin C, along with its cyclin dependent kinase partner Cdk8, associates with the RNA polymerase holoenzyme to regulate transcription. In particular, cyclin C-Cdk8 repress many stress responsive genes. To relieve this repression, cyclin C is destroyed in cells exposed to pro-oxidants and other stressors. However, prior to its destruction, cyclin C, but not Cdk8, is released from its nuclear anchor (Med13, translocates from the nucleus to the cytoplasm where it interacts with the fission machinery and is both necessary and sufficient to induce extensive mitochondria fragmentation. Furthermore, cytoplasmic cyclin C promotes PCD indicating that it mediates both mitochondrial fission and cell death pathways. This review will summarize the role cyclin C plays in regulating stress-responsive transcription. In addition, we will detail

WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for Mitochondrial Fusion

Directory of Open Access Journals (Sweden)

Guorui Huang

2017-07-01

Full Text Available Regulated inter-mitochondrial fusion/fission is essential for maintaining optimal mitochondrial respiration and control of apoptosis and autophagy. In mammals, mitochondrial fusion is controlled by outer membrane GTPases MFN1 and MFN2 and by inner membrane (IM GTPase OPA1. Disordered mitochondrial fusion/fission contributes to various pathologies, and MFN2 or OPA1 mutations underlie neurodegenerative diseases. Here, we show that the WBSCR16 protein is primarily associated with the outer face of the inner mitochondrial membrane and is important for mitochondrial fusion. We provide evidence of a WBSCR16/OPA1 physical interaction in the intact cell and of a WBSCR16 function as an OPA1-specific guanine nucleotide exchange factor (GEF. Homozygosity for a Wbscr16 mutation causes early embryonic lethality, whereas neurons of mice heterozygous for the mutation have mitochondria with reduced membrane potential and increased susceptibility to fragmentation upon exposure to stress, suggesting roles for WBSCR16 deficits in neuronal pathologies.

Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model.

Science.gov (United States)

Komulainen, Tuomas; Lodge, Tiffany; Hinttala, Reetta; Bolszak, Maija; Pietilä, Mika; Koivunen, Peppi; Hakkola, Jukka; Poulton, Joanna; Morten, Karl J; Uusimaa, Johanna

2015-05-04

Sodium valproate (VPA) is a potentially hepatotoxic antiepileptic drug. Risk of VPA-induced hepatotoxicity is increased in patients with mitochondrial diseases and especially in patients with POLG1 gene mutations. We used a HepG2 cell in vitro model to investigate the effect of VPA on mitochondrial activity. Cells were incubated in glucose medium and mitochondrial respiration-inducing medium supplemented with galactose and pyruvate. VPA treatments were carried out at concentrations of 0-2.0mM for 24-72 h. In both media, VPA caused decrease in oxygen consumption rates and mitochondrial membrane potential. VPA exposure led to depleted ATP levels in HepG2 cells incubated in galactose medium suggesting dysfunction in mitochondrial ATP production. In addition, VPA exposure for 72 h increased levels of mitochondrial reactive oxygen species (ROS), but adversely decreased protein levels of mitochondrial superoxide dismutase SOD2, suggesting oxidative stress caused by impaired elimination of mitochondrial ROS and a novel pathomechanism related to VPA toxicity. Increased cell death and decrease in cell number was detected under both metabolic conditions. However, immunoblotting did not show any changes in the protein levels of the catalytic subunit A of mitochondrial DNA polymerase γ, the mitochondrial respiratory chain complexes I, II and IV, ATP synthase, E3 subunit dihydrolipoyl dehydrogenase of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase and glutathione peroxidase. Our results show that VPA inhibits mitochondrial respiration and leads to mitochondrial dysfunction, oxidative stress and increased cell death, thus suggesting an essential role of mitochondria in VPA-induced hepatotoxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Transfer-induced fission in inverse kinematics: Impact on experimental and evaluated nuclear data bases

Energy Technology Data Exchange (ETDEWEB)

Farget, F.; Schmidt, K.H.; Clement, E.; Delaune, O.; Derkx, X.; Dijon, A.; Golabek, C.; Lemasson, A.; Roger, T.; Schmitt, C. [CEA/DSM-CNRS/IN2P3, GANIL, Caen (France); Caamano, M.; Ramos, D.; Benlliure, J.; Cortina, D.; Fernandez-Dominguez, B.; Paradela, C. [Universidade de Santiago de Compostela, Santiago de Compostela (Spain); Rodriguez-Tajes, C. [CEA/DSM-CNRS/IN2P3, GANIL, Caen (France); Universidade de Santiago de Compostela, Santiago de Compostela (Spain); Audouin, L. [Universite Paris-Sud 11, CNRS/IN2P3, Institut de Physique Nucleaire, Orsay (France); Casarejos, E. [Universidade de Vigo, Vigo (Spain); Dore, D.; Salsac, M.D. [Centre de Saclay, CEA, Irfu, Gif-sur-Yvette (France); Gaudefroy, L. [CEA DAM Ile-de-France, BP 12, Bruyeres-le-Chatel (France); Heinz, A. [Chalmers Tekniska Hoegskola, Fundamental Fysik, Goeteborg (Sweden); Jurado, B. [Universite Bordeaux, CENBG, UMR 5797 CNRS/IN2P3, Gradignan (France)

2015-12-15

Inverse kinematics is a new tool to study nuclear fission. Its main advantage is the possibility to measure with an unmatched resolution the atomic number of fission fragments, leading to new observables in the properties of fission-fragment distributions. In addition to the resolution improvement, the study of fission based on nuclear collisions in inverse kinematics beneficiates from a larger view with respect to the neutron-induced fission, as in a single experiment the number of fissioning systems and the excitation energy range are widden. With the use of spectrometers, mass and kinetic-energy distributions may now be investigated as a function of the proton and neutron number sharing. The production of fissioning nuclei in transfer reactions allows studying the isotopic yields of fission fragments as a function of the excitation energy. The higher excitation energy resulting in the fusion reaction leading to the compound nucleus {sup 250}Cf at an excitation energy of 45MeV is also presented. With the use of inverse kinematics, the charge polarisation of fragments at scission is now revealed with high precision, and it is shown that it cannot be neglected, even at higher excitation energies. In addition, the kinematical properties of the fragments inform on the deformation configuration at scission. (orig.)

Ebselen induces mitochondrial permeability transition because of its interaction with adenine nucleotide translocase.

Science.gov (United States)

Pavón, Natalia; Correa, Francisco; Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Chávez, Edmundo

2015-10-15

Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening. Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A. At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase. Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier. Copyright © 2015 Elsevier Inc. All rights reserved.

Prompt fissionγ-ray characteristics from neutron-induced fission on 239Pu and the time-dependence of prompt-γray emission

Science.gov (United States)

Gatera, Angélique; Göök, Alf; Hambsch, Franz-Josef; Moens, André; Oberstedt, Andreas; Oberstedt, Stephan; Sibbens, Goedele; Vanleeuw, David; Vidali, Marzio

2018-03-01

Recent years have seen an increased interest in prompt fission γ-ray (PFG) measurements motivated by a high priority request of the OECD/NEA for high precision data, mainly for the nuclear fuel isotopes 235U and 239Pu. Our group has conducted a PFG measurement campaign using state-of-the-art lanthanum halide detectors for all the main actinides to a precision better than 3%. The experiments were performed in a coincidence setup between a fission trigger and γ-ray detectors. The time-of-flight technique was used to discriminate photons, traveling at the speed of light, and prompt fission neutrons. For a full rejection of all neutrons below 20 MeV, the PFG time window should not be wider than a few nanoseconds. This window includes most PFG, provided that no isomeric states were populated during the de-excitation process. When isomeric states are populated, PFGs can still be emitted up to 1 yus after the instant of fission or later. To study these γ-rays, the detector response to neutrons had to be determined and a correction had to be applied to the γ-ray spectra. The latest results for PFG characteristics from the reaction 239Pu(nth,f) will be presented, together with an analysis of PFGs emitted up to 200 ns after fission in the spontaneous fission of 252Cf as well as for thermal-neutron induced fission on 235U and 239Pu. The results are compared with calculations in the framework of the Hauser-Feshbach Monte Carlo code CGMF and FIFRELIN.

Simulated production rates of exotic nuclei from the ion guide for neutron-induced fission at IGISOL

Energy Technology Data Exchange (ETDEWEB)

Jansson, Kaj; Al-Adili, Ali; Nilsson, Nicklas; Norlin, Martin; Solders, Andreas [Uppsala University, Department of Physics and Astronomy, Uppsala (Sweden)

2017-12-15

An investigation of the stopping efficiency of fission products, in the new ion guide designed for ion production through neutron-induced fission at IGISOL in Jyvaeskylae, Finland, has been conducted. Our simulations take into account the new neutron converter, enabling measurements of neutron-induced fission yields, and thereby provide estimates of the obtained yields as a function of primary proton beam current. Different geometries, targets, and pressures, as well as models for the effective charge of the stopped ions were tested, and optimisations to the setup for higher yields are suggested. The predicted number of ions stopped in the gas lets us estimate the survival probability of the ions reaching the downstream measurements stations. (orig.)

Importance of mitochondrial calcium uniporter in high glucose-induced endothelial cell dysfunction.

Science.gov (United States)

Chen, Wei; Yang, Jie; Chen, Shuhua; Xiang, Hong; Liu, Hengdao; Lin, Dan; Zhao, Shaoli; Peng, Hui; Chen, Pan; Chen, Alex F; Lu, Hongwei

2017-11-01

Mitochondrial Ca 2+ overload is implicated in hyperglycaemia-induced endothelial cell dysfunction, but the key molecular events responsible remain unclear. We examined the involvement of mitochondrial calcium uniporter, which mediates mitochondrial Ca 2+ uptake, in endothelial cell dysfunction resulting from high-glucose treatment. Human umbilical vein endothelial cells were exposed to various glucose concentrations and to high glucose (30 mM) following mitochondrial calcium uniporter inhibition or activation with ruthenium red and spermine, respectively. Subsequently, mitochondrial calcium uniporter and mitochondrial calcium uniporter regulator 1 messenger RNA and protein expression was measured by real-time polymerase chain reaction and western blotting. Ca 2+ concentrations were analysed by laser confocal microscopy, and cytoplasmic and mitochondrial oxidative stress was detected using 2',7'-dichlorofluorescein diacetate and MitoSOX Red, respectively. Apoptosis was assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and a wound-healing assay was performed using an in vitro model. High glucose markedly upregulated mitochondrial calcium uniporter and mitochondrial calcium uniporter regulator 1 messenger RNA expression, as well as protein production, in a dose- and time-dependent manner with a maximum effect demonstrated at 72 h and 30 mM glucose concentration. Moreover, high-glucose treatment significantly raised both mitochondrial and cytoplasmic Ca 2+ and reactive oxygen species levels, increased apoptosis and compromised wound healing (all p calcium uniporter, respectively. Mitochondrial calcium uniporter plays an important role in hyperglycaemia-induced endothelial cell dysfunction and may constitute a therapeutic target to reduce vascular complications in diabetes.

Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

KAUST Repository

Papsdorf, Katharina

2015-09-03

Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntington’s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

Fission product induced swelling of U–Mo alloy fuel

International Nuclear Information System (INIS)

Kim, Yeon Soo; Hofman, G.L.

2011-01-01

Highlights: ► We measured fuel swelling of U–Mo alloy by fission products at temperatures below 250 °C. ► We quantified the swelling portion of U–Mo by fission gas bubbles. ► We developed an empirical model as a function of fission density. - Abstract: Fuel swelling of U–Mo alloy was modeled using the measured data from samples irradiated up to a fission density of ∼7 × 10 27 fissions/m 3 at temperatures below ∼250 °C. The overall fuel swelling was measured from U–Mo foils with as-fabricated thickness of 250 μm. Volume fractions occupied by fission gas bubbles were measured and fuel swelling caused by the fission gas bubbles was quantified. The portion of fuel swelling by solid fission products including solid and liquid fission products as well as fission gas atoms not enclosed in the fission gas bubbles is estimated by subtracting the portion of fuel swelling by gas bubbles from the overall fuel swelling. Empirical correlations for overall fuel swelling, swelling by gas bubbles, and swelling by solid fission products were obtained in terms of fission density.

Measurements of fission product yield in the neutron-induced fission of 238U with average energies of 9.35 MeV and 12.52 MeV

Science.gov (United States)

Mukerji, Sadhana; Krishnani, Pritam Das; Shivashankar, Byrapura Siddaramaiah; Mulik, Vikas Kaluram; Suryanarayana, Saraswatula Venkat; Naik, Haladhara; Goswami, Ashok

2014-07-01

The yields of various fission products in the neutron-induced fission of 238U with the flux-weightedaveraged neutron energies of 9.35 MeV and 12.52 MeV were determined by using an off-line gammaray spectroscopic technique. The neutrons were generated using the 7Li(p, n) reaction at Bhabha Atomic Research Centre-Tata Institute of Fundamental Research Pelletron facility, Mumbai. The gamma- ray activities of the fission products were counted in a highly-shielded HPGe detector over a period of several weeks to identify the decaying fission products. At both the neutron energies, the fission-yield values are reported for twelve fission product. The results obtained from the present work have been compared with the similar data for mono-energetic neutrons of comparable energy from the literature and are found to be in good agreement. The peak-to-valley (P/V) ratios were calculated from the fission-yield data and were found to decreases for neutron energy from 9.35 to 12.52 MeV, which indicates the role of excitation energy. The effect of the nuclear structure on the fission product-yield is discussed.

Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease.

Science.gov (United States)

Sverdlov, Aaron L; Elezaby, Aly; Qin, Fuzhong; Behring, Jessica B; Luptak, Ivan; Calamaras, Timothy D; Siwik, Deborah A; Miller, Edward J; Liesa, Marc; Shirihai, Orian S; Pimentel, David R; Cohen, Richard A; Bachschmid, Markus M; Colucci, Wilson S

2016-01-11

Mitochondrial reactive oxygen species (ROS) are associated with metabolic heart disease (MHD). However, the mechanism by which ROS cause MHD is unknown. We tested the hypothesis that mitochondrial ROS are a key mediator of MHD. Mice fed a high-fat high-sucrose (HFHS) diet develop MHD with cardiac diastolic and mitochondrial dysfunction that is associated with oxidative posttranslational modifications of cardiac mitochondrial proteins. Transgenic mice that express catalase in mitochondria and wild-type mice were fed an HFHS or control diet for 4 months. Cardiac mitochondria from HFHS-fed wild-type mice had a 3-fold greater rate of H2O2 production (P=0.001 versus control diet fed), a 30% decrease in complex II substrate-driven oxygen consumption (P=0.006), 21% to 23% decreases in complex I and II substrate-driven ATP synthesis (P=0.01), and a 62% decrease in complex II activity (P=0.002). In transgenic mice that express catalase in mitochondria, all HFHS diet-induced mitochondrial abnormalities were ameliorated, as were left ventricular hypertrophy and diastolic dysfunction. In HFHS-fed wild-type mice complex II substrate-driven ATP synthesis and activity were restored ex vivo by dithiothreitol (5 mmol/L), suggesting a role for reversible cysteine oxidative posttranslational modifications. In vitro site-directed mutation of complex II subunit B Cys100 or Cys103 to redox-insensitive serines prevented complex II dysfunction induced by ROS or high glucose/high palmitate in the medium. Mitochondrial ROS are pathogenic in MHD and contribute to mitochondrial dysfunction, at least in part, by causing oxidative posttranslational modifications of complex I and II proteins including reversible oxidative posttranslational modifications of complex II subunit B Cys100 and Cys103. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Ursolic Acid-enriched herba cynomorii extract induces mitochondrial uncoupling and glutathione redox cycling through mitochondrial reactive oxygen species generation: protection against menadione cytotoxicity in h9c2 cells.

Science.gov (United States)

Chen, Jihang; Wong, Hoi Shan; Ko, Kam Ming

2014-01-27

Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

Angular distribution of fragments from neutron-induced fission of {sup 238}U in the intermediate energy region

Energy Technology Data Exchange (ETDEWEB)

Carlsson, Magnus

2004-06-01

Areas ranging from nuclear structure models to accelerator-driven systems benefit from improved neutron-induced fission data in the intermediate energy region. In this Master's degree thesis, the fragment angular distribution from fission of {sup 238}U, induced by 21-MeV neutrons, has been analysed from an experiment performed with the Medley/DIFFICILE setup at the The Svedberg Laboratory in Uppsala. The data have been corrected for low energy neutrons in the beam. The results agree with other experiments, as well as with model calculations. The data should be a starting point for further analysis with a goal to deduce the fission cross-section of {sup 238}U.

Fission energy of uranium isotopes and transuranium elements

International Nuclear Information System (INIS)

Nemirovskij, P.Eh.; Manevich, L.G.

1981-01-01

A comparison is made between the prompt fission energy, Esub(pr), calculated from the mass and binding energy spectrum and the Esub(pr) value obtained from the experimental data on the kinetic energy of fragments, the energy of prompt neutrons and prompt γ-quanta. Basing on the data on β-decay chains of fission fragments, the energies of neutrinos, γ-quanta and β-electrons are obtained, which permits to calculate the actual energy released during fission. The calculations are performed for thermal neutron-induced fission, fast-neutron induced fission and for fission after bombardment with 14 MeV neutrons. The available experimental data on the fission fragment kinetic energy, prompt γ-quanta energy and fission neutron energy are presented. The comparison of the Esub(pr) values obtained experimentally for the thermal-neutron-induced fission with the calculated Esub(pr) value shows that for 233 U, 239 Pu, 241 Pu the agreement is rather favourable. For 235 U the agreement is within the error limits. As to the Esub(pr) values for the fast-neutron-induced fission, the agreement between the calculated and experimental data for all nuclides is quite good

Characterization of canine mitochondrial protein expression in natural and induced forms of idiopathic dilated cardiomyopathy.

Science.gov (United States)

Lopes, Rosana; Solter, Philip F; Sisson, D David; Oyama, Mark A; Prosek, Robert

2006-06-01

To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and induced dilated cardiomyopathy (DCM). Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with induced DCM. Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by >or= 2-fold between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. Within narrow pH gradients of control canine heart mitochondrial samples, a total of 1,528 protein spots were revealed. Forty subunits of heart mitochondrial proteins that differ significantly from control tissues were altered in tissue specimens from dogs with naturally occurring and induced forms of DCM. The most affected heart mitochondrial proteins in both groups were those of oxidative phosphorylation (55%). Upregulation of manganese superoxide dismutase was suggestive of heart oxidative injury in tissue specimens from dogs with both forms of DCM. Evidence of apoptosis was associated with overexpression of the heart mitochondrial voltage-dependent anion channel-2 protein and endonuclease G in tissue specimens from dogs with induced DCM. Alterations of heart mitochondrial proteins related to oxidative phosphorylation dysfunction were more prevalent in tissue specimens from dogs with induced or naturally occurring DCM, compared with those of control dogs.

Lowered iPLA2γ activity causes increased mitochondrial lipid peroxidation and mitochondrial dysfunction in a rotenone-induced model of Parkinson's disease.

Science.gov (United States)

Chao, Honglu; Liu, Yinlong; Fu, Xian; Xu, Xiupeng; Bao, Zhongyuan; Lin, Chao; Li, Zheng; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

2018-02-01

iPLA 2 γ, calcium-independent phospholipase A 2 γ, discerningly hydrolyses glycerophospholipids to liberate free fatty acids. iPLA 2 γ-deficiency has been associated with abnormal mitochondrial function. More importantly, the iPLA 2 family is causative proteins in mitochondrial neurodegenerative disorders such as parkinsonian disorders. However, the mechanisms by which iPLA 2 γ affects Parkinson's disease (PD) remain unknown. Mitochondrion stress has a key part in rotenone-induced dopaminergic neuronal degeneration. The present evaluation revealed that lowered iPLA 2 γ function provokes the parkinsonian phenotype and leads to the reduction of dopamine and its metabolites, lowered survival, locomotor deficiencies, and organismal hypersensitivity to rotenone-induced oxidative stress. In addition, lowered iPLA 2 γ function escalated the amount of mitochondrial irregularities, including mitochondrial reactive oxygen species (ROS) regeneration, reduced ATP synthesis, reduced glutathione levels, and abnormal mitochondrial morphology. Further, lowered iPLA 2 γ function was tightly linked with strengthened lipid peroxidation and mitochondrial membrane flaws following rotenone treatment, which can cause cytochrome c release and eventually apoptosis. These results confirmed the important role of iPLA 2 γ, whereby decreasing iPLA 2 γ activity aggravates mitochondrial degeneration to induce neurodegenerative disorders in a rotenone rat model of Parkinson's disease. These findings may be useful in the design of rational approaches for the prevention and treatment of PD-associated symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

STING-IRF3 Triggers Endothelial Inflammation in Response to Free Fatty Acid-Induced Mitochondrial Damage in Diet-Induced Obesity

Science.gov (United States)

Mao, Yun; Luo, Wei; Zhang, Lin; Wu, Weiwei; Yuan, Liangshuai; Xu, Hao; Song, Juhee; Fujiwara, Keigi; Abe, Jun-ichi; LeMaire, Scott A.; Wang, Xing Li; Shen, Ying. H.

2017-01-01

Objective Metabolic stress in obesity induces endothelial inflammation and activation, which initiates adipose tissue inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms underlying endothelial inflammation induction are not completely understood. Stimulator of interferon genes (STING) is an important molecule in immunity and inflammation. In the present study, we sought to determine the role of STING in palmitic acid (PA)-induced endothelial activation/inflammation. Approach and Results In cultured endothelial cells, PA treatment activated STING, as indicated by its perinuclear translocation and binding to interferon regulatory factor 3 (IRF3), leading to IRF3 phosphorylation and nuclear translocation. The activated IRF3 bound to the promoter of intercellular adhesion molecule 1 (ICAM-1) and induced ICAM-1 expression and monocyte–endothelial cell adhesion. When analyzing the upstream signaling, we found that PA activated STING by inducing mitochondrial damage. PA treatment caused mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol. Through the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), the mitochondrial damage and leaked cytosolic mtDNA activated the STING-IRF3 pathway and increased ICAM-1 expression. In mice with diet-induced obesity, the STING-IRF3 pathway was activated in adipose tissue. However, STING deficiency (Stinggt/gt) partially prevented diet-induced adipose tissue inflammation, obesity, insulin resistance, and glucose intolerance. Conclusions The mitochondrial damage-cGAS-STING-IRF3 pathway is critically involved in metabolic stress-induced endothelial inflammation. STING may be a potential therapeutic target for preventing cardiovascular diseases and insulin resistance in obese individuals. PMID:28302626

Fast-twitch glycolytic skeletal muscle is predisposed to age-induced impairments in mitochondrial function

DEFF Research Database (Denmark)

Jacobs, Robert A; Díaz, Víctor; Soldini, Lavinia

2013-01-01

The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high-resolution respirom......The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high......-resolution respirometry and mitochondrial protein expression in soleus, quadricep, and lateral gastrocnemius skeletal muscles, which represent type 1 slow-twitch oxidative muscle (soleus) and type 2 fast-twitch glycolytic muscle (quadricep and gastrocnemius), respectively, in young (10-12 weeks) and mature (74-76 weeks......) mice. Electron transport through mitochondrial complexes I and III increases with age in quadricep and gastrocnemius, which is not observed in soleus. Mitochondrial coupling efficiency during respiration through complex I also deteriorates with age in gastrocnemius and shows a tendency (p = .085...

Development of a “Fission-proxy” Method for the Measurement of 14-MeV Neutron Fission Yields at CAMS

Energy Technology Data Exchange (ETDEWEB)

Gharibyan, Narek [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-10-25

Relative fission yield measurements were made for 50 fission products from 25.6±0.5 MeV alpha-induced fission of Th-232. Quantitative comparison of these experimentally measured fission yields with the evaluated fission yields from 14-MeV neutron-induced fission of U-235 demonstrates the feasibility of the proposed fission-proxy method. This new technique, based on the Bohr-independence hypothesis, permits the measurement of fission yields from an alternate reaction pathway (Th-232 + 25.6 MeV α → U-236* vs. U-235 + 14-MeV n → U-236*) given that the fission process associated with the same compound nucleus is independent of its formation. Other suitable systems that can potentially be investigated in this manner include (but are not limited to) Pu-239 and U-237.

Post-scission fission theory: Neutron emission in fission

International Nuclear Information System (INIS)

Madland, D.G.

1997-01-01

A survey of theoretical representations of two of the observables in neutron emission in fission is given, namely, the prompt fission neutron spectrum N (E) and the average prompt neutron multiplicity bar ν p . Early representations of the two observables are presented and their deficiencies are discussed. This is followed by summaries and examples of recent theoretical models for the calculation of these quantities. Emphasis is placed upon the predictability and accuracy of the recent models. In particular, the dependencies of N (E) and bar ν p upon the fissioning nucleus and its excitation energy are treated. Recent work in the calculation of the prompt fission neutron spectrum matrix N (E, E n ), where E n is the energy of the neutron inducing fission, is then discussed. Concluding remarks address the current status of our ability to calculate these observables with confidence, the direction of future theoretical efforts, and limitations to current (and future) approaches

Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

LENUS (Irish Health Repository)

Gorman, Sheeona

2012-02-01

The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

Use of a Novel Two Color PALM Method to Examine Structural Properties of Drp1 Helical Rings during Mammalian Mitochondrial Fission In Situ

Science.gov (United States)

Rosenbloom, Alyssa Blair

In this thesis, we accomplish two goals: 1) we develop a novel two color photoactivatable light microscopy (PALM) method for imaging in mammalian cells and 2) we explore our original biological question and discern the structural properties of the Drp1 helical ring during fission. We established that mitochondrial membranes can be distinguished with the available photoactivatable fluorescent protein mEos2. However, we were not able to use any of the published photoactivatable and photoswitchable green fluorescent proteins, predominantly because of an inability to identify individual fluorescent events due to rapidity of the photoswitiching. Based on published crystal structures, we created novel Dronpa variants with increasing steric hindrance around the chromophore, likely partially inhibiting the isomerization. We replaced Val157 with isoleucine, leucine, or phenyalanine. DronpaV157F showed no fluorescence and was discarded. DronpaV157I and DronpaV157L showed photoswitchable green fluorescence, with individual fluorescent events that were more easily discerned. DronpaV157L in particular had bright fluorescent events that were well separated when imaged in mammalian cells at 20 Hz. We named this new variant rsKame. Using PALM we successfully imaged rsKame expressed and localized to the mammalian mitochondrial inner membrane. With the novel photoswitchable fluorescent protein, rsKame, available, we returned to the development of a novel two color PALM method. We chose PAmCherry1 as the partner for rsKame since PAmCherry1 has distinct and well separated excitation/emission spectra from rsKame and is not activated by low 405 nm laser power density. We first imaged rsKame with 405 nm activation at (0.61 mW/mm2) and 488 nm activation/excitation (5.87 W/mm 2) to completion. We then imaged PAmCherry1 with increasing 405 nm activation (0.6-6.0 W/mm2) and 561 nm excitation (22 W/mm 2). With the novel PALM imaging method, we labeled the inner and outer mitochondrial

Induced fission track distribution from highly radioactive particles in fallout materials

International Nuclear Information System (INIS)

Hashimoto, Tetsuo; Okada, Tatemichi

1987-01-01

Some highly radioactive fallout particles (GPs) from the 19th Chinese nuclear detonation were followed to the neutron irradiation in a reactor after sandwiched with mica detectors. The interesting star-like fission track patterns were revealed on the etched surface of the mica detectors. The simple chemical separation procedure for the GPs was applied for the separation of U and Pu as fissile elements and the both resultant fractions were examined with the similar high sensitive fission tracking detection. Subsequently, a representative track pattern from a black spherical particle was subjected to the determination of fissile nuclide content; comparing the total fission events evaluated on the basis of the numerical calculation of track densities with the total thermal neutron fluence. The results implied that the uranium is responsible for the main fissile nuclide remaining within a particle as unfissioned fractions and should be certainly enriched with respect to U-235 within such small fallout particles. This sophisticated method was also applied to determine the dead GPs, which have been highly radioactive particles just after the detonations, in the rain and snow-residual materials. Many induced star-like fission tracks verified certainly that there remains a lot of dead particles in the atmosheric environment till nowadays. (author)

ALDH2 restores exhaustive exercise-induced mitochondrial dysfunction in skeletal muscle

International Nuclear Information System (INIS)

Zhang, Qiuping; Zheng, Jianheng; Qiu, Jun; Wu, Xiahong; Xu, Yangshuo; Shen, Weili; Sun, Mengwei

2017-01-01

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is highly expressed in heart and skeletal muscles, and is the major enzyme that metabolizes acetaldehyde and toxic aldehydes. The cardioprotective effects of ALDH2 during cardiac ischemia/reperfusion injury have been recognized. However, less is known about the function of ALDH2 in skeletal muscle. This study was designed to evaluate the effect of ALDH2 on exhaustive exercise-induced skeletal muscle injury. Methods: We created transgenic mice expressing ALDH2 in skeletal muscles. Male wild-type C57/BL6 (WT) and ALDH2 transgenic mice (ALDH2-Tg), 8-weeks old, were challenged with exhaustive exercise for 1 week to induce skeletal muscle injury. Animals were sacrificed 24 h post-exercise and muscle tissue was excised. Results: ALDH2-Tg mice displayed significantly increased treadmill exercise capacity compared to WT mice. Exhaustive exercise caused an increase in mRNA levels of the muscle atrophy markers, Atrogin-1 and MuRF1, and reduced mitochondrial biogenesis and fusion in WT skeletal muscles; these effects were attenuated in ALDH2-Tg mice. Exhaustive exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of Beclin1 and Bnip3; the effects of which were mitigated by ALDH2 overexpression. In addition, ALDH2-Tg reversed the increase of an oxidative stress biomarker (4-hydroxynonenal) and decreased levels of mitochondrial antioxidant proteins, including manganese superoxide dismutase and NAD(P)H:quinone oxidoreductase 1, in skeletal muscle induced by exhaustive exercise. Conclusion: ALDH2 may reverse skeletal muscle mitochondrial dysfunction due to exhaustive exercise by regulating mitochondria dynamic remodeling and enhancing the quality of mitochondria. - Highlights: • Skeletal muscle ALDH2 expression and activity declines during exhaustive exercise. • ALDH2 overexpression enhances physical performance and restores muscle

Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.

Science.gov (United States)

Santini, Alessandro; Ronchi, Dario; Garbellini, Manuela; Piga, Daniela; Protti, Alessandro

2017-07-01

Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia. In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level. During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.

Measurements of fission product yield in the neutron-induced fission of {sup 238}U with average energies of 9.35 MeV and 12.52 MeV

Energy Technology Data Exchange (ETDEWEB)

Mukerji, Sadhana; Krishnani, Pritam Das; Suryanarayana, Saraswatula Venkat; Naik, Haladhara; Goswami, Ashok [Bhabha Atomic Research Centre, Mumbai (India); Shivashankar, Byrapura Siddaramaiah [Manipal University, Manipal (India); Mulik, Vikas Kaluram [University of Pune, Pune (India)

2014-07-15

The yields of various fission products in the neutron-induced fission of {sup 238}U with the flux-weighted averaged neutron energies of 9.35 MeV and 12.52 MeV were determined by using an off-line gamma ray spectroscopic technique. The neutrons were generated using the {sup 7}Li(p, n) reaction at Bhabha Atomic Research Centre-Tata Institute of Fundamental Research Pelletron facility, Mumbai. The gamma- ray activities of the fission products were counted in a highly-shielded HPGe detector over a period of several weeks to identify the decaying fission products. At both the neutron energies, the fission-yield values are reported for twelve fission product. The results obtained from the present work have been compared with the similar data for mono-energetic neutrons of comparable energy from the literature and are found to be in good agreement. The peak-to-valley (P/V) ratios were calculated from the fission-yield data and were found to decreases for neutron energy from 9.35 to 12.52 MeV, which indicates the role of excitation energy. The effect of the nuclear structure on the fission product-yield is discussed.

Proton-induced fission cross sections on "2"0"8Pb at high kinetic energies

International Nuclear Information System (INIS)

Rodriguez-Sanchez, J.L.; Benlliure, J.; Paradela, C.; Ayyad, Y.; Alvarez-Pol, H.; Cortina-Gil, D.; Pietras, B.; Ramos, D.; Vargas, J.; Taieb, J.; Chatillon, A.; Belier, G.; Boutoux, G.; Gorbinet, T.; Laurent, B.; Martin, J.F.; Pellereau, E.; Casarejos, E.; Rodriguez-Tajes, C.

2014-01-01

Total fission cross sections of "2"0"8Pb induced by protons have been determined at 370 A, 500 A, and 650 A MeV. The experiment was performed at GSI Darmstadt where the combined use of the inverse kinematics technique with an efficient detection setup allowed us to determine these cross sections with an uncertainty below 6%. This result was achieved by an accurate beam selection and registration of both fission fragments in coincidence which were also clearly distinguished from other reaction channels. These data solve existing discrepancies between previous measurements, providing new values for the Prokofiev systematics. The data also allow us to investigate the fission process at high excitation energies and small deformations. In particular, some fundamental questions about fission dynamics have been addressed, which are related to dissipative and transient time effects. (authors)

The total kinetic energy release in the fast neutron-induced fission of {sup 232}Th

Energy Technology Data Exchange (ETDEWEB)

King, Jonathan; Yanez, Ricardo; Loveland, Walter; Barrett, J. Spencer; Oscar, Breland [Oregon State University, Dept. of Chemistry, Corvallis, OR (United States); Fotiades, Nikolaos; Tovesson, Fredrik; Young Lee, Hye [Los Alamos National Laboratory, Physics Division, Los Alamos, NM (United States)

2017-12-15

The post-emission total kinetic energy release (TKE) in the neutron-induced fission of {sup 232}Th was measured (using white spectrum neutrons from LANSCE) for neutron energies from E{sub n} = 3 to 91 MeV. In this energy range the average post-neutron total kinetic energy release decreases from 162.3 ± 0.3 at E{sub n} = 3 MeV to 154.9 ± 0.3 MeV at E{sub n} = 91 MeV. Analysis of the fission mass distributions indicates that the decrease in TKE with increasing neutron energy is a combination of increasing yields of symmetric fission (which has a lower associated TKE) and a decrease in the TKE release in asymmetric fission. (orig.)

FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis.

Science.gov (United States)

Chattaragada, M S; Riganti, C; Sassoe, M; Principe, M; Santamorena, M M; Roux, C; Curcio, C; Evangelista, A; Allavena, P; Salvia, R; Rusev, B; Scarpa, A; Cappello, P; Novelli, F

2018-02-08

Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified 'family with sequence similarity 49 member B' (FAM49B) as a mitochondria-localized protein that regulates mitochondrial fission and cancer progression. Silencing FAM49B in PDAC cells resulted in increased fission and mitochondrial ROS generation, which enhanced PDAC cell proliferation and invasion. Notably, FAM49B expression levels in PDAC cells were downregulated by the tumor microenvironment. Overall, the results of this study show that FAM49B acts as a suppressor of cancer cell proliferation and invasion in PDAC by regulating tumor mitochondrial redox reactions and metabolism.

14.2 MeV neutron induced U-235 fission cross section measurement

International Nuclear Information System (INIS)

Li Jingwen; Shen Guanren; Ye Zongyuan; Li Anli; Zhou Shuhua; Sun Zhongfan; Wu Jingxia; Huang Tanzi

1986-01-01

The cross section of U-235 fission induced by 14.2 MeV neutrons was measured by the time correlated associated particle method. The result obtained is (2.078+-0.040) barn. Comparison with other author's is also given. (author)

Intermediate energy nuclear fission

International Nuclear Information System (INIS)

Hylten, G.

1982-01-01

Nuclear fission has been investigated with the double-kinetic-energy method using silicon surface barrier detectors. Fragment energy correlation measurements have been made for U, Th and Bi with bremsstrahlung of 600 MeV maximum energy. Distributions of kinetic energy as a function of fragment mass are presented. The results are compared with earlier photofission data and in the case of bismuth, with calculations based on the liquid drop model. The binary fission process in U, Yb, Tb, Ce, La, Sb, Ag and Y induced by 600 MeV protons has been investigated yielding fission cross sections, fragment kinetic energies, angular correlations and mass distributions. Fission-spallation competition calculations are used to deduce values of macroscopic fission barrier heights and nuclear level density parameter values at deformations corresponding to the saddle point shapes. We find macroscopic fission barriers lower than those predicted by macroscopic theories. No indication is found of the Businaro Gallone limit expected to occur somewhere in the mass range A = 100 to A = 140. For Ce and La asymmetric mass distributions similar to those in the actinide region are found. A method is described for the analysis of angular correlations between complementary fission products. The description is mainly concerned with fission induced by medium-energy protons but is applicable also to other projectiles and energies. It is shown that the momentum and excitation energy distributions of cascade residuals leading to fission can be extracted. (Author)

Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.

Science.gov (United States)

Sedlic, Filip; Muravyeva, Maria Y; Sepac, Ana; Sedlic, Marija; Williams, Anna Marie; Yang, Meiying; Bai, Xiaowen; Bosnjak, Zeljko J

2017-01-01

Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption, and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP, and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes. J. Cell. Physiol. 232: 216-224, 2017

Fission cross section measurements at intermediate energies

International Nuclear Information System (INIS)

Laptev, Alexander

2005-01-01

The activity in intermediate energy particle induced fission cross-section measurements of Pu, U isotopes, minor actinides and sub-actinides in PNPI of Russia is reviewed. The neutron-induced fission cross-section measurements are under way in the wide energy range of incident neutrons from 0.5 MeV to 200 MeV at the GNEIS facility. In number of experiments at the GNEIS facility, the neutron-induced fission cross sections were obtained for many nuclei. In another group of experiments the proton-induced fission cross-section have been measured for proton energies ranging from 200 to 1000 MeV at 100 MeV intervals using the proton beam of PNPI synchrocyclotron. (author)

Fission yield measurements at IGISOL

Science.gov (United States)

Lantz, M.; Al-Adili, A.; Gorelov, D.; Jokinen, A.; Kolhinen, V. S.; Mattera, A.; Moore, I.; Penttilä, H.; Pomp, S.; Prokofiev, A. V.; Rakopoulos, V.; Rinta-Antila, S.; Simutkin, V.; Solders, A.

2016-06-01

The fission product yields are an important characteristic of the fission process. In fundamental physics, knowledge of the yield distributions is needed to better understand the fission process. For nuclear energy applications good knowledge of neutroninduced fission-product yields is important for the safe and efficient operation of nuclear power plants. With the Ion Guide Isotope Separator On-Line (IGISOL) technique, products of nuclear reactions are stopped in a buffer gas and then extracted and separated by mass. Thanks to the high resolving power of the JYFLTRAP Penning trap, at University of Jyväskylä, fission products can be isobarically separated, making it possible to measure relative independent fission yields. In some cases it is even possible to resolve isomeric states from the ground state, permitting measurements of isomeric yield ratios. So far the reactions U(p,f) and Th(p,f) have been studied using the IGISOL-JYFLTRAP facility. Recently, a neutron converter target has been developed utilizing the Be(p,xn) reaction. We here present the IGISOL-technique for fission yield measurements and some of the results from the measurements on proton induced fission. We also present the development of the neutron converter target, the characterization of the neutron field and the first tests with neutron-induced fission.

Fission yield measurements at IGISOL

Directory of Open Access Journals (Sweden)

Lantz M.

2016-01-01

Full Text Available The fission product yields are an important characteristic of the fission process. In fundamental physics, knowledge of the yield distributions is needed to better understand the fission process. For nuclear energy applications good knowledge of neutroninduced fission-product yields is important for the safe and efficient operation of nuclear power plants. With the Ion Guide Isotope Separator On-Line (IGISOL technique, products of nuclear reactions are stopped in a buffer gas and then extracted and separated by mass. Thanks to the high resolving power of the JYFLTRAP Penning trap, at University of Jyväskylä, fission products can be isobarically separated, making it possible to measure relative independent fission yields. In some cases it is even possible to resolve isomeric states from the ground state, permitting measurements of isomeric yield ratios. So far the reactions U(p,f and Th(p,f have been studied using the IGISOL-JYFLTRAP facility. Recently, a neutron converter target has been developed utilizing the Be(p,xn reaction. We here present the IGISOL-technique for fission yield measurements and some of the results from the measurements on proton induced fission. We also present the development of the neutron converter target, the characterization of the neutron field and the first tests with neutron-induced fission.

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

Science.gov (United States)

Liu, Y; Cheng, H; Zhou, Y; Zhu, Y; Bian, R; Chen, Y; Li, C; Ma, Q; Zheng, Q; Zhang, Y; Jin, H; Wang, X; Chen, Q; Zhu, D

2013-01-01

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells. PMID:23412387

Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.

Directory of Open Access Journals (Sweden)

Suzana Gispert

Full Text Available BACKGROUND: Parkinson's disease (PD is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1 cause the recessive PARK6 variant of PD. METHODOLOGY/PRINCIPAL FINDINGS: Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. CONCLUSION: Thus, aging Pink1(-/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.

Determination of the fast-neutron-induced fission cross-section of 242Pu at nELBE

Science.gov (United States)

Kögler, Toni; Beyer, Roland; Junghans, Arnd R.; Schwengner, Ronald; Wagner, Andreas

2018-03-01

The fast-neutron-induced fission cross section of 242Pu was determined in the energy range of 0.5 MeV to 10MeV at the neutron time-of-flight facility nELBE. Using a parallel-plate fission ionization chamber this quantity was measured relative to 235U(n,f). The number of target nuclei was thereby calculated by means of measuring the spontaneous fission rate of 242Pu. An MCNP 6 neutron transport simulation was used to correct the relative cross section for neutron scattering. The determined results are in good agreement with current experimental and evaluated data sets.

Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons

Science.gov (United States)

Ito, Hiroyuki; Uchida, Tokujiro; Makita, Koshi

2015-01-01

Purpose Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated. Methods Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy. Results Twenty-four-hour exposure of iPSC-derived neurons to 500 μM ketamine resulted in a 40% increase in caspase 3/7 activity (P ketamine (100 μM) decreased the ATP level (22%, P ketamine concentration, which suggests that mitochondrial dysfunction preceded ROS generation and caspase activation. Conclusions We established an in vitro model for assessing the neurotoxicity of ketamine in iPSC-derived neurons. The present data indicate that the initial mitochondrial dysfunction and autophagy may be related to its inhibitory effect on the mitochondrial electron transport system, which underlies ketamine-induced neural toxicity. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons. PMID:26020236

Progress in fission product nuclear data

International Nuclear Information System (INIS)

Lammer, M.

1984-09-01

This is the tenth issue of a report series on Fission Product Data, which informs us about all the activities in this field, which are planned, ongoing, or have recently been completed. The types of activities included are measurements, compilations and evaluations of: fission product yields (neutron induced and spontaneous fission), neutron reaction cross sections of fission products, data related to the radioactive decay of fission products, delayed neutron data of fission products, lumped fission product data (decay heat, absorption, etc.). There is also a section with recent references relative to fission product nuclear data

Neutron-induced fission fragment angular distribution at CERN n TOF: The Th-232 case

CERN Document Server

Tarrio, Diego; Paradela, Carlos

This thesis work was done in the frame of the study of the neutron-induced fission of actinides and subactinides at the CERN n TOF facility using a fast Parallel Plate Avalanche Counters (PPACs) setup. This experimental setup provide us with an intense neutron beam with a white spectrum from thermal to 1 GeV and with an outstanding high resolution provided by its flight path of 185 m. In our experiment, fission events were identified by detection of both fission fragments in time coincidence in the two PPAC detectors flanking the corresponding target. This technique allowed us to discriminate the fission events from the background produced by α disintegration of radioactive samples and by particles produced in spallation reactions. Because PPAC detectors are insensitive to the γ flash, it is possible to reach energies as high as 1 GeV. The stripped cathodes provide the spatial position of the hits in the detectors, so that the emission angle of the fission fragments can be measured. Inside the reaction cham...

Fission fragment angular distributions and fission cross section validation

International Nuclear Information System (INIS)

Leong, Lou Sai

2013-01-01

The present knowledge of angular distributions of neutron-induced fission is limited to a maximal energy of 15 MeV, with large discrepancies around 14 MeV. Only 238 U and 232 Th have been investigated up to 100 MeV in a single experiment. The n-TOF Collaboration performed the fission cross section measurement of several actinides ( 232 Th, 235 U, 238 U, 234 U, 237 Np) at the n-TOF facility using an experimental set-up made of Parallel Plate Avalanche Counters (PPAC), extending the energy domain of the incident neutron above hundreds of MeV. The method based on the detection of the 2 fragments in coincidence allowed to clearly disentangle the fission reactions among other types of reactions occurring in the spallation domain. I will show the methods we used to reconstruct the full angular resolution by the tracking of fission fragments. Below 10 MeV our results are consistent with existing data. For example in the case of 232 Th, below 10 MeV the results show clearly the variation occurring at the first (1 MeV) and second (7 MeV) chance fission, corresponding to transition states of given J and K (total spin and its projection on the fission axis), and a much more accurate energy dependence at the 3. chance threshold (14 MeV) has been obtained. In the spallation domain, above 30 MeV we confirm the high anisotropy revealed in 232 Th by the single existing data set. I'll discuss the implications of this finding, related to the low anisotropy exhibited in proton-induced fission. I also explore the critical experiments which is valuable checks of nuclear data. The 237 Np neutron-induced fission cross section has recently been measured in a large energy range (from eV to GeV) at the n-TOF facility at CERN. When compared to previous measurements, the n-TOF fission cross section appears to be higher by 5-7 % beyond the fission threshold. To check the relevance of n-TOF data, we simulate a criticality experiment performed at Los Alamos with a 6 kg sphere of 237 Np. This

Estrogen-related receptor α is essential for maintaining mitochondrial integrity in cisplatin-induced acute kidney injury.

Science.gov (United States)

Tsushida, Keigo; Tanabe, Katsuyuki; Masuda, Kana; Tanimura, Satoshi; Miyake, Hiromasa; Arata, Yuka; Sugiyama, Hitoshi; Wada, Jun

2018-04-15

Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin. Male C57BL/6 J wild-type and ERRα -/- mice received a single intraperitoneal injection of 20 mg/kg cisplatin. Seventy-two hours after the injection, kidney function and morphology were evaluated. ERRα expression was observed in renal tubules, and cisplatin inhibited its translocation into nuclei. ERRα deficiency exacerbated cisplatin-induced renal dysfunction and tubular injury, as well as oxidative stress and apoptosis. ERRα -/- mice kidneys revealed lower mitochondrial DNA content and swollen mitochondria with reduced cristae. In addition, these mice had lower expression of the mitochondrial fusion protein mitofusin-2. The cisplatin-induced decrease in mitochondrial DNA and altered mitochondrial structure were more severe in ERRα -/- mice. In cultured mouse proximal tubular epithelial cells, the ERRα inverse agonist XCT-790 significantly inhibited mitofusin-2 expression and induced mitochondrial fragmentation. Taken together, our findings suggest the involvement of ERRα in the progression of cisplatin-induced AKI probably through impaired mitochondrial dynamics. Copyright © 2018 Elsevier Inc. All rights reserved.

Trap-induced photoconductivity in singlet fission pentacene diodes

Energy Technology Data Exchange (ETDEWEB)

Qiao, Xianfeng, E-mail: qiaoxianfeng@hotmail.com; Zhao, Chen; Chen, Bingbing; Luan, Lin [WuHan National Laboratory for Optoelectronics and School of Optical and Electronic Information, Huazhong University of Science and Technology, Wu Han 430074 (China)

2014-07-21

This paper reports a trap-induced photoconductivity in ITO/pentacene/Al diodes by using current-voltage and magneto-conductance measurements. The comparison of photoconductivity between pentacene diodes with and without trap clearly shows that the traps play a critical role in generating photoconductivity. It shows that no observable photoconductivity is detected for trap-free pentacene diodes, while significant photoconductivity is observed in diodes with trap. This is because the initial photogenerated singlet excitons in pentacene can rapidly split into triplet excitons with higher binding energy prior to dissociating into free charge carriers. The generated triplet excitons react with trapped charges to release charge-carriers from traps, leading to a trap-induced photoconductivity in the single-layer pentacene diodes. Our studies elucidated the formation mechanisms of photoconductivity in pentacene diodes with extremely fast singlet fission rate.

Energy dependence of the neutron multiplicity P/sub nu/ in fast neutron induced fission of /sup 235,238/U and 239Pu

International Nuclear Information System (INIS)

Zucker, M.S.; Holden, N.E.

1986-01-01

Certain applications require knowledge of the higher moments of the neutron multiplicity probability. It can be shown that the second factorial moment is proportional to the fission rate in the sample, and that the third factorial moment can be of use in disentangling spontaneous fission from induced fission. Using a source of unpublished work in which neutron multiplicities were derived for the fast neutron induced fission of U-235, U-238, and Pu-239, the multiplicity probability has been calculated as a function of neutron energy for the energy range 0 to 10 MeV

Basic physics of the fission process. Chapter 2

International Nuclear Information System (INIS)

Michaudon, A.

1981-01-01

A general description of the fission process is given with special emphasis on those aspects which are necessary for the understanding of the measurements and calculations of neutron-induced fission cross-sections. Having considered the various phases of the process, some typical properties of the low-energy fission of actinide nuclei are presented and the more specific features of neutron induced fission are examined. (U.K.)

Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles

Science.gov (United States)

Wilson, Christina L.; Natarajan, Vaishaali; Hayward, Stephen L.; Khalimonchuk, Oleh; Kidambi, Srivatsan

2015-11-01

Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 +/- 10.56 ppm, 136.0 +/- 31.73 ppm and 62.37 +/- 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction.Titanium dioxide (Ti

HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

International Nuclear Information System (INIS)

Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

2007-01-01

Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF 2α ) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF 2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production

Co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins in the lactation-induced mitochondrial hypotrophy of rat brown fat.

Science.gov (United States)

Martin, I; Giralt, M; Viñas, O; Iglesias, R; Mampel, T; Villarroya, F

1995-01-01

The relative abundance of the mitochondrial-encoded mRNAs for cytochrome c oxidase subunit II and NADH dehydrogenase subunit I was lower in brown adipose tissue (BAT) from lactating rats than in virgin controls. This decrease was in parallel with a significant decrease in mitochondrial 16 S rRNA levels and in the relative content of mitochondrial DNA in the tissue. BAT from lactating rats showed lowered mRNA expression of the nuclear-encoded genes for the mitochondrial uncoupling protein, subunit IV of cytochrome c oxidase and the adenine nucleotide translocase isoforms ANT1 and ANT2, whereas mRNA levels for the ATP synthase beta-subunit were unchanged. However, the relative content of this last protein was lower in BAT mitochondria from lactating rats than in virgin controls. It is concluded that lactation-induced mitochondrial hypotrophy in BAT is associated with a co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins. This decrease is caused by regulatory events acting at different levels, including pre- and post-transcriptional regulation. BAT appears to be a useful model with which to investigate the molecular mechanisms involved in the co-ordination of the expression of the mitochondrial and nuclear genomes during mitochondrial biogenesis. Images Figure 1 Figure 2 PMID:8948428

Neutron-induced Fission Cross Sections of Am and Cm isotopes (Final Report of Research Contract 14485). Resonance and Fast Neutron Induced Fission Cross Sections of Americium and Curium Nuclides (Third-year Progress Report of Research Contract 14485)

International Nuclear Information System (INIS)

Alekseev, A.A.; Bergman, A.A.; Berlev, A.I.; Koptelov, E.A.; Egorov, A.S.; Samylin, B.F.; Trufanov, A.M.; Fursov, B.I.; Shorin, V.S.

2012-01-01

The neutron induced fission cross sections of Am and Cm isotopes were measured relative to 239 Pu in the neutron energy range from 1 eV to 20 keV at the INR RAS lead slowing down spectrometer LSDS-100. The fission resonance integrals were also estimated using the measured cross section data. The results have been compared with the available experimental and evaluated data. This analysis has shown the present status of the measured fission cross sections and the necessity to revise the evaluated cross sections libraries for the minor actinides. (author)

Oleuropein isolated from Fraxinus rhynchophylla inhibits glutamate-induced neuronal cell death by attenuating mitochondrial dysfunction.

Science.gov (United States)

Kim, Mi Hye; Min, Ju-Sik; Lee, Joon Yeop; Chae, Unbin; Yang, Eun-Ju; Song, Kyung-Sik; Lee, Hyun-Shik; Lee, Hong Jun; Lee, Sang-Rae; Lee, Dong-Seok

2017-04-27

Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases.

Prompt fission neutron spectra from fission induced by 1 to 8 MeV neutrons on 235U and 239Pu using the double time-of-flight technique

International Nuclear Information System (INIS)

Noda, S.; Haight, R. C.; Nelson, R. O.; Devlin, M.; O'Donnell, J. M.; Chatillon, A.; Granier, T.; Belier, G.; Taieb, J.; Kawano, T.; Talou, P.

2011-01-01

Prompt fission neutron spectra from 235 U and 239 Pu were measured for incident neutron energies from 1 to 200 MeV at the Weapons Neutron Research facility (WNR) of the Los Alamos Neutron Science Center, and the experimental data were analyzed with the Los Alamos model for the incident neutron energies of 1-8 MeV. A CEA multiple-foil fission chamber containing deposits of 100 mg 235 U and 90 mg 239 Pu detected fission events. Outgoing neutrons were detected by the Fast Neutron-Induced γ-Ray Observer array of 20 liquid organic scintillators. A double time-of-flight technique was used to deduce the neutron incident energies from the spallation target and the outgoing energies from the fission chamber. These data were used for testing the Los Alamos model, and the total kinetic energy parameters were optimized to obtain a best fit to the data. The prompt fission neutron spectra were also compared with the Evaluated Nuclear Data File (ENDF/B-VII.0). We calculate average energies from both experimental and calculated fission neutron spectra.

New fission-neutron-spectrum representation for ENDF

International Nuclear Information System (INIS)

Madland, D.G.

1982-04-01

A new representation of the prompt fission neutron spectrum is proposed for use in the Evaluated Nuclear Data File (ENDF). The proposal is made because a new theory exists by which the spectrum can be accurately predicted as a function of the fissioning nucleus and its excitation energy. Thus, prompt fission neutron spectra can be calculated for cases where no measurements exist or where measurements are not possible. The mathematical formalism necessary for application of the new theory within ENDF is presented and discussed for neutron-induced fission and spontaneous fission. In the case of neutron-induced fission, expressions are given for the first-chance, second-chance, third-chance, and fourth-chance fission components of the spectrum together with that for the total spectrum. An ENDF format is proposed for the new fission spectrum representation, and an example of the use of the format is given

Determination of the fast-neutron-induced fission cross-section of 242Pu at nELBE

Directory of Open Access Journals (Sweden)

Kögler Toni

2018-01-01

Full Text Available The fast-neutron-induced fission cross section of 242Pu was determined in the energy range of 0.5 MeV to 10MeV at the neutron time-of-flight facility nELBE. Using a parallel-plate fission ionization chamber this quantity was measured relative to 235U(n,f. The number of target nuclei was thereby calculated by means of measuring the spontaneous fission rate of 242Pu. An MCNP 6 neutron transport simulation was used to correct the relative cross section for neutron scattering. The determined results are in good agreement with current experimental and evaluated data sets.

Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

OpenAIRE

Park, Jung Hyun; Ku, Hyeong Jun; Lee, Jin Hyup; Park, Jeen-Woo

2017-01-01

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the ro...

Fission dynamics in the proton induced fission of heavy nuclei

Energy Technology Data Exchange (ETDEWEB)

Rubchenya, V.A. E-mail: rubchen@phys.jyu.fi; Trzaska, W.H.; Itkis, I.M.; Itkis, M.G.; Kliman, J.; Kniajeva, G.N.; Kondratiev, N.A.; Kozulin, E.M.; Krupa, L.; Pokrovski, I.V.; Voskressenski, V.M.; Hanappe, F.; Materna, T.; Dorvaux, O.; Stuttge, L.; Chubarian, G.; Khlebnikov, S.V.; Vakhtin, D.N.; Lyapin, V.G

2004-04-05

Multi-parameter correlation study of the reaction {sup 242}Pu(p, f) at E{sub p} 13, 20 and 55 MeV has been carried out. Fission fragment mass and kinetic energy distributions and the double differential neutron spectra have been measured. It was observed that the two-humped shape of mass distributions prevailed up to highest proton energy. Manifestation of the nuclear shell Z 28 near fragment mass A{sub fr} = 70 has been detected. The experimental results were analyzed in the framework of a time-dependent statistical model with inclusion of nuclear friction effects in the fission process. The multi-parameter correlation study of the reaction.

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

Science.gov (United States)

Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

2015-01-01

HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

Modulation of cadmium-induced mitochondrial dysfunction and volume changes by temperature in rainbow trout (Oncorhynchus mykiss)

International Nuclear Information System (INIS)

Onukwufor, John O.; Kibenge, Fred; Stevens, Don; Kamunde, Collins

2015-01-01

Highlights: • Interactions of Cd and temperature exacerbate mitochondrial dysfunction and enhance Cd accumulation. • Cd uptake by mitochondria occurs through the Ca uniporter. • Temperature exacerbates Cd-induced mitochondrial volume changes. • Low concentrations of Cd inhibit mitochondrial swelling. - Abstract: We investigated how temperature modulates cadmium (Cd)-induced mitochondrial bioenergetic disturbances, metal accumulation and volume changes in rainbow trout (Oncorhynchus mykiss). In the first set of experiments, rainbow trout liver mitochondrial function and Cd content were measured in the presence of complex I substrates, malate and glutamate, following exposure to Cd (0–100 μM) at three (5, 13 and 25 °C) temperatures. The second set of experiments assessed the effect of temperature on Cd-induced mitochondrial volume changes, including the underlying mechanisms, at 15 and 25 °C. Although temperature stimulated both state 3 and 4 rates of respiration, the coupling efficiency was reduced at temperature extremes due to greater inhibition of state 3 at low temperature and greater stimulation of state 4 at the high temperature. Cadmium exposure reduced the stimulatory effect of temperature on state 3 respiration but increased that on state 4, consequently exacerbating mitochondrial uncoupling. The interaction of Cd and temperature yielded different responses on thermal sensitivity of state 3 and 4 respiration; the Q 10 values for state 3 respiration increased at low temperature (5–13 °C) while those for state 4 increased at high temperature (13–25 °C). Importantly, the mitochondria accumulated more Cd at high temperature suggesting that the observed greater impairment of oxidative phosphorylation with temperature was due, at least in part, to a higher metal burden. Cadmium-induced mitochondrial volume changes were characterized by an early phase of contraction followed by swelling, with temperature changing the kinetics and intensifying

Modulation of cadmium-induced mitochondrial dysfunction and volume changes by temperature in rainbow trout (Oncorhynchus mykiss)

Energy Technology Data Exchange (ETDEWEB)

Onukwufor, John O. [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kamunde, Collins, E-mail: ckamunde@upei.ca [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada)

2015-01-15

Highlights: • Interactions of Cd and temperature exacerbate mitochondrial dysfunction and enhance Cd accumulation. • Cd uptake by mitochondria occurs through the Ca uniporter. • Temperature exacerbates Cd-induced mitochondrial volume changes. • Low concentrations of Cd inhibit mitochondrial swelling. - Abstract: We investigated how temperature modulates cadmium (Cd)-induced mitochondrial bioenergetic disturbances, metal accumulation and volume changes in rainbow trout (Oncorhynchus mykiss). In the first set of experiments, rainbow trout liver mitochondrial function and Cd content were measured in the presence of complex I substrates, malate and glutamate, following exposure to Cd (0–100 μM) at three (5, 13 and 25 °C) temperatures. The second set of experiments assessed the effect of temperature on Cd-induced mitochondrial volume changes, including the underlying mechanisms, at 15 and 25 °C. Although temperature stimulated both state 3 and 4 rates of respiration, the coupling efficiency was reduced at temperature extremes due to greater inhibition of state 3 at low temperature and greater stimulation of state 4 at the high temperature. Cadmium exposure reduced the stimulatory effect of temperature on state 3 respiration but increased that on state 4, consequently exacerbating mitochondrial uncoupling. The interaction of Cd and temperature yielded different responses on thermal sensitivity of state 3 and 4 respiration; the Q{sub 10} values for state 3 respiration increased at low temperature (5–13 °C) while those for state 4 increased at high temperature (13–25 °C). Importantly, the mitochondria accumulated more Cd at high temperature suggesting that the observed greater impairment of oxidative phosphorylation with temperature was due, at least in part, to a higher metal burden. Cadmium-induced mitochondrial volume changes were characterized by an early phase of contraction followed by swelling, with temperature changing the kinetics and

Development of ionization technique for measurement of fast neutron induced fission products yields of {sup 237}Np

Energy Technology Data Exchange (ETDEWEB)

Goverdovski, A.A.; Khryachkov, V.A.; Ketlerov, V.V.; Mitrofanov, V.F.; Ostapenko, Yu.B.; Semenova, N.N.; Fomichev, A.N.; Rodina, L.F. [Institute of Physics and Power Engineering, Obninsk (Russian Federation)

1997-03-01

Twin gridded ionization chamber and corresponding software was designed for measurements of masses, kinetic energies and nuclear charges of fission fragments from fast neutron induced fission of {sup 237}Np. The ionization detector design, electronics, data acquisition and processing system and the test results are presented in this paper. (J.P.N.)

Possible viscosity effects in neutron-induced fission of 232Th and 238U

International Nuclear Information System (INIS)

Gindler, J.E.; Glendenin, L.E.; Wilkins, B.D.

1979-01-01

Fission yields induced in the 238 U(n,f) and 232 Th(n,f) reactions were determined as a function of incident neutron energy (E/sub n/). The ratio of 115 Cd-to- 140 Ba yields as a function of E/sub n/ is analyzed by means of the equation Y 1 /Y 2 = exp[2(a 1 (E/sub n/+E 1 )/sup 1/2/ -2(a 2 (E/sub n/+E 2 )/sup 1/2/] to give values of a/sub i/, the level density parameter, and E/sub i/, the excitation energy for E/sub n/=0. The energies E/sub i/ are interpreted on the basis of the liquid drop model with shell and pairing corrections. Values are deduced for the energy dissipated by viscosity effects in the descent from the saddle point to the point where masses are fixed in the fissioning nucleus. These values are 1.7 MeV for 232 Th(n,f) and 4.8 MeV for 238 U(n,f). These values are consistent with the experimental observation that anti ν/sub p/ is approx. 0.6 neutron greater for 239 U fission than for 233 Th fission and that strong odd--even (nucleon pairing) effects are found in the fragment total kinetic energy distribution for 230 Th fission but not for 234 U fission. The low dissipation energy values together with the low values of pre-scission kinetic energy deduced by Guet, et al., [Nucl. Phys. A134 (1971)1] indicate a shorter path from the saddle point of the fissioning nucleus to scission than is generally assumed in theoretical calculations. 31 references

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

Energy Technology Data Exchange (ETDEWEB)

Gan, Xueqi; Huang, Shengbin; Yu, Qing [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States); State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yu, Haiyang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yan, Shirley ShiDu, E-mail: shidu@ku.edu [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States)

2015-12-25

Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.

Inhibition of mitochondrial division through covalent modification of Drp1 protein by 15 deoxy-Δ12,14-prostaglandin J2

International Nuclear Information System (INIS)

Mishra, Nandita; Kar, Rekha; Singha, Prajjal K.; Venkatachalam, Manjeri A.; McEwen, Donald G.; Saikumar, Pothana

2010-01-01

Arachidonic acid derived endogenous electrophile 15d-PGJ2 has gained much attention in recent years due to its potent anti-proliferative and anti-inflammatory actions mediated through thiol modification of cysteine residues in its target proteins. Here, we show that 15d-PGJ2 at 1 μM concentration converts normal mitochondria into large elongated and interconnected mitochondria through direct binding to mitochondrial fission protein Drp1 and partial inhibition of its GTPase activity. Mitochondrial elongation induced by 15d-PGJ2 is accompanied by increased assembly of Drp1 into large oligomeric complexes through plausible intermolecular interactions. The role of decreased GTPase activity of Drp1 in the formation of large oligomeric complexes is evident when Drp1 is incubated with a non-cleavable GTP analog, GTPγS or by a mutation that inactivated GTPase activity of Drp1 (K38A). The mutation of cysteine residue (Cys644) in the GTPase effector domain, a reported target for modification by reactive electrophiles, to alanine mimicked K38A mutation induced Drp1 oligomerization and mitochondrial elongation, suggesting the importance of cysteine in GED to regulate the GTPase activity and mitochondrial morphology. Interestingly, treatment of K38A and C644A mutants with 15d-PGJ2 resulted in super oligomerization of both mutant Drp1s indicating that 15d-PGJ2 may further stabilize Drp1 oligomers formed by loss of GTPase activity through covalent modification of middle domain cysteine residues. The present study documents for the first time the regulation of a mitochondrial fission activity by a prostaglandin, which will provide clues for understanding the pathological and physiological consequences of accumulation of reactive electrophiles during oxidative stress, inflammation and degeneration.

Fission product yield measurements using monoenergetic photon beams

Science.gov (United States)

Krishichayan; Bhike, M.; Tonchev, A. P.; Tornow, W.

2017-09-01

Measurements of fission products yields (FPYs) are an important source of information on the fission process. During the past couple of years, a TUNL-LANL-LLNL collaboration has provided data on the FPYs from quasi monoenergetic neutron-induced fission on 235U, 238U, and 239Pu and has revealed an unexpected energy dependence of both asymmetric fission fragments at energies below 4 MeV. This peculiar FPY energy dependence was more pronounced in neutron-induced fission of 239Pu. In an effort to understand and compare the effect of the incoming probe on the FPY distribution, we have carried out monoenergetic photon-induced fission experiments on the same 235U, 238U, and 239Pu targets. Monoenergetic photon beams of Eγ = 13.0 MeV were provided by the HIγS facility, the world's most intense γ-ray source. In order to determine the total number of fission events, a dual-fission chamber was used during the irradiation. These irradiated samples were counted at the TUNL's low-background γ-ray counting facility using high efficient HPGe detectors over a period of 10 weeks. Here we report on our first ever photofission product yield measurements obtained with monoenegetic photon beams. These results are compared with neutron-induced FPY data.

Fission product yield measurements using monoenergetic photon beams

Directory of Open Access Journals (Sweden)

Krishichayan

2017-01-01

Full Text Available Measurements of fission products yields (FPYs are an important source of information on the fission process. During the past couple of years, a TUNL-LANL-LLNL collaboration has provided data on the FPYs from quasi monoenergetic neutron-induced fission on 235U, 238U, and 239Pu and has revealed an unexpected energy dependence of both asymmetric fission fragments at energies below 4 MeV. This peculiar FPY energy dependence was more pronounced in neutron-induced fission of 239Pu. In an effort to understand and compare the effect of the incoming probe on the FPY distribution, we have carried out monoenergetic photon-induced fission experiments on the same 235U, 238U, and 239Pu targets. Monoenergetic photon beams of Eγ = 13.0 MeV were provided by the HIγS facility, the world's most intense γ-ray source. In order to determine the total number of fission events, a dual-fission chamber was used during the irradiation. These irradiated samples were counted at the TUNL's low-background γ-ray counting facility using high efficient HPGe detectors over a period of 10 weeks. Here we report on our first ever photofission product yield measurements obtained with monoenegetic photon beams. These results are compared with neutron-induced FPY data.

Ternary fission

International Nuclear Information System (INIS)

Wagemans, C.

1991-01-01

Since its discovery in 1946, light (charged) particle accompanied fission (ternary fission) has been extensively studied, for spontaneous as well as for induced fission reactions. The reason for this interest was twofold: the ternary particles being emitted in space and time close to the scission point were expected to supply information on the scission point configuration and the ternary fission process was an important source of helium, tritium, and hydrogen production in nuclear reactors, for which data were requested by the nuclear industry. Significant experimental progress has been realized with the advent of high-resolution detectors, powerful multiparameter data acquisition systems, and intense neutron and photon beams. As far as theory is concerned, the trajectory calculations (in which scission point parameters are deduced from the experimental observations) have been very much improved. An attempt was made to explain ternary particle emission in terms of a Plateau-Rayleigh hydrodynamical instability of a relatively long cylindrical neck or cylindrical nucleus. New results have also been obtained on the so-called open-quotes trueclose quotes ternary fission (fission in three about-equal fragments). The spontaneous emission of charged particles has also clearly been demonstrated in recent years. This chapter discusses the main characteristics of ternary fission, theoretical models, light particle emission probabilities, the dependence of the emission probabilities on experimental variables, light particle energy distributions, light particle angular distributions, correlations between light particle accompanied fission observables, open-quotes trueclose quotes ternary fission, and spontaneous emission of heavy ions. 143 refs., 18 figs., 8 tabs

Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: Prevention by thiol group protecting agents

International Nuclear Information System (INIS)

Custodio, Jose B.A.; Cardoso, Carla M.P.; Santos, Maria S.; Almeida, Leonor M.; Vicente, Joaquim A.F.; Fernandes, Maria A.S.

2009-01-01

Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca 2+ -induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20 nmol/mg protein) induced Ca 2+ -dependent mitochondrial swelling, depolarization of membrane potential (ΔΨ), Ca 2+ release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40 nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the ΔΨ, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H 2 O 2 generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca 2+ -induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA.

Science.gov (United States)

Karavaeva, Iuliia E; Golyshev, Sergey A; Smirnova, Ekaterina A; Sokolov, Svyatoslav S; Severin, Fedor F; Knorre, Dmitry A

2017-04-01

Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8 , ATG32 or ATG33 , implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes. © 2017. Published by The Company of Biologists Ltd.

Measurements of neutron-induced capture and fission reactions on $^{235}$ U: cross sections and ${\\alpha}$ ratios, photon strength functions and prompt ${\\gamma}$-ray from fission

CERN Multimedia

We propose to measure the neutron-induced capture cross section of the fissile isotope $^{235}$U using a fission tagging set-up. This new set-up has been tested successfully in 2010 and combines the n_TOF 4${\\pi}$ Total Absorption Calorimeter (TAC) with MicroMegas (MGAS) fission detectors. It has been proven that such a combination of detectors allows distinguishing with very good reliability the electromagnetic cascades from the capture reactions from dominant ${\\gamma}$-ray background coming from the fission reactions. The accurate discrimination of the fission background is the main challenge in the neutron capture cross section measurements of fissile isotopes. The main results from the measurement will be the associated capture cross section and ${\\alpha}$ ratio in the resolved (0.3-2250 eV) and unresolved (2.25-30 keV) resonance regions. According to the international benchmarks and as it is mentioned in the NEA High Priority Request List (HPRL), the 235U(n,${\\gamma}$) cross section is of utmost impo...

Determination of the neutron-induced fission cross section of {sup 242}Pu; Bestimmung des neutroneninduzierten Spaltquerschnitts von {sup 242}Pu

Energy Technology Data Exchange (ETDEWEB)

Koegler, Toni Joerg

2016-04-26

Neutron induced fission cross sections of actinides like the Pu-isotopes are of relevance for the development of nuclear transmutation technologies. For {sup 242}Pu, current uncertainties are of around 21%. Sensitivity studies show that the total uncertainty has to be reduced to below 5% to allow for reliable neutron physics simulations. This challenging task was performed at the neutron time-of-flight facility of the new German National Center for High Power Radiation Sources at HZDR, Dresden. Within the TRAKULA project, thin, large and homogeneous deposits of {sup 235}U and {sup 242}Pu have been produced successfully. Using two consecutively placed fission chambers allowed the determination of the neutron induced fission cross section of {sup 242}Pu relative to {sup 235}U. The areal density of the Plutonium targets was calculated using the measured spontaneous fission rate. Experimental results of the fast neutron induced fission of {sup 242}Pu acquired at nELBE will be presented and compared to recent experiments and evaluated data. Corrections addressing the neutron scattering are discussed by using results of different neutron transport simulations (Geant 4, MCNP 6 and FLUKA).

Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

Directory of Open Access Journals (Sweden)

Lamiaa A Ahmed

Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

Angular Distribution of Gamma Rays from the Fission of {sup 235}U Induced by 14-Mev Neutrons

Energy Technology Data Exchange (ETDEWEB)

Jeki, L.; Kluge, Gy.; Lajtai, A. [Central Research Institute for Physics, Hungarian Academy of Sciences (Hungary)

1969-12-15

Experiments are reported which were performed to study the angular distribution of the gamma radiation following fast-neutron-induced nuclear fission. The investigations were, in particular, focussed on the influence which the angular momentum imparted to the compound nucleus by the fast neutrons has on the angular distribution of the {gamma}-rays. The fission of {sup 235}U is induced by 14-MeV-energy neutrons from the T(d, n) {alpha} reaction. The fission fragments are detected by a gas-scintillation counter filled with a mixture of Ar and Ni gases, the {gamma}-rays by 5 cm x 5 cm Nal(Tl) crystal with an energy threshold of 120 keV. The intensity of the {gamma}-rays is measured at 90 Degree-Sign and 174 Degree-Sign to the direction of fragment motion. The flight times of fission neutrons and {gamma}-rays are measured with a 20-ns overlap-type time-to-pulse height converter while the background was covered simultaneously with another converter delayed with respect to the former. The signals from both converters are analysed by a multichannel analyser with divisible memory. The flight path, which is chosen to be about 70 cm, makes it possible to separate the neutron from the gamma counts. The geometry is designed to keep the direction of the outflying fission fragments nearly the same as that of the incident fast neutrons. In this way the angular momenta of the fast neutrons are normal to the flight path of the fragments. The measured gamma intensities are extrapolated to 180 Degree-Sign on a computer using Strutinski's formula n( Greek-Theta-Symbol ) {approx}1 + B sin Greek-Theta-Symbol . On transformation of the measured data from the laboratory system to the system of fragments the anisotropy is found to be A = 1(180 Degree-Sign )/l (90 Degree-Sign ) = 1.33 {+-} 0.05. The main angular momentum of fission fragments is calculated from the anisotropy as 15 h units. As compared with the thermal-neutron-induced fission the present results indicate an additional

Mitochondrial Morphology and Fundamental Parameters of the Mitochondrial Respiratory Chain Are Altered in Caenorhabditis elegans Strains Deficient in Mitochondrial Dynamics and Homeostasis Processes.

Directory of Open Access Journals (Sweden)

Anthony L Luz

Full Text Available Mitochondrial dysfunction has been linked to myriad human diseases and toxicant exposures, highlighting the need for assays capable of rapidly assessing mitochondrial health in vivo. Here, using the Seahorse XFe24 Analyzer and the pharmacological inhibitors dicyclohexylcarbodiimide and oligomycin (ATP-synthase inhibitors, carbonyl cyanide 4-(trifluoromethoxy phenylhydrazone (mitochondrial uncoupler and sodium azide (cytochrome c oxidase inhibitor, we measured the fundamental parameters of mitochondrial respiratory chain function: basal oxygen consumption, ATP-linked respiration, maximal respiratory capacity, spare respiratory capacity and proton leak in the model organism Caenhorhabditis elegans. Since mutations in mitochondrial homeostasis genes cause mitochondrial dysfunction and have been linked to human disease, we measured mitochondrial respiratory function in mitochondrial fission (drp-1-, fusion (fzo-1-, mitophagy (pdr-1, pink-1-, and electron transport chain complex III (isp-1-deficient C. elegans. All showed altered function, but the nature of the alterations varied between the tested strains. We report increased basal oxygen consumption in drp-1; reduced maximal respiration in drp-1, fzo-1, and isp-1; reduced spare respiratory capacity in drp-1 and fzo-1; reduced proton leak in fzo-1 and isp-1; and increased proton leak in pink-1 nematodes. As mitochondrial morphology can play a role in mitochondrial energetics, we also quantified the mitochondrial aspect ratio for each mutant strain using a novel method, and for the first time report increased aspect ratios in pdr-1- and pink-1-deficient nematodes.

Cross section of ternary fission of Al, Ti, Co and Zr nuclei induced by 0,8 - 1,8 Gev photons

International Nuclear Information System (INIS)

Lima, D.A. de; Sousa, E.V. de; Milomen, W.C.C.; Tavares, O.A.P.

1988-01-01

A research on ternary fission of Al, Ti, Co, and Zr nuclei induced by bremsstrahlung photons of 0,8, 1,0, 1,4, and 1,8 Gev end-point energies has been carried out using makrofol polycarbonate and CR-39 polymer as fission-track detectors. Results are discussed and compared with other ternary fission data. (M.W.O.) [pt

Mitochondrial electron transport chain is involved in microcystin-RR induced tobacco BY-2 cells apoptosis.

Science.gov (United States)

Huang, Wenmin; Li, Dunhai; Liu, Yongding

2014-09-01

Microcystin-RR (MC-RR) has been suggested to induce apoptosis in tobacco BY-2 cells through mitochondrial dysfunction including the loss of mitochondrial membrane potential (ΔΨm). To further elucidate the mechanisms involved in MC-RR induced apoptosis in tobacco BY-2 cells, we have investigated the role of mitochondrial electron transport chain (ETC) as a potential source for reactive oxygen species (ROS). Tobacco BY-2 cells after exposure to MC-RR (60mg/L) displayed apoptotic changes in association with an increased production of ROS and loss of ΔΨm. All of these adverse effects were significantly attenuated by ETC inhibitors including Rotenone (2μmol/L, complex I inhibitor) and antimycin A (0.01μmol/L, complex III inhibitor), but not by thenoyltrifluoroacetone (5μmol/L, complex II inhibitor). These results suggest that mitochondrial ETC plays a key role in mediating MC-RR induced apoptosis in tobacco BY-2 cells through an increased mitochondrial production of ROS. Copyright © 2014. Published by Elsevier B.V.

Investigation of the fission yields of the fast neutron-induced fission of {sup 233}U; Mesure de la distribution en masse et en charge des produits de la fission rapide de l'{sup 233}U

Energy Technology Data Exchange (ETDEWEB)

Galy, J

1999-09-01

As a stars, a survey of the different methods of investigations of the fission product yields and the experimental data status have been studied, showing advantages and shortcomings for the different approaches. An overview of the existing models for the fission product distributions has been as well intended. The main part of this thesis was the measurement of the independent yields of the fast neutron-induced fission of{sup 233}U, never investigated before this work. The experiment has been carried out using the mass separator OSIRIS (Isotope Separator On-Line). Its integrated ion-source and its specific properties required an analysis of the delay-parameter and ionisation efficiency for each chemical species. On the other hand, this technique allows measurement of independent yields and cumulative yields for elements from Cu to Ba, covering most of the fission yield distribution. Thus, we measured about 180 independent yields from Zn (Z=30) to Sr (Z=38) in the mass range A=74-99 and from Pd (Z=46) to Ba (Z=56) in the mass range A=113-147, including many isomeric states. An additional experiment using direct {gamma}-spectroscopy of aggregates of fission products was used to determine more than 50 cumulative yields of element with half-life from 15 min to a several days. All experimental data have been compared to estimates from a semi-empirical model, to calculated values and to evaluated values from the European library JEF 2.2. Furthermore, a study of both thermal and fast neutron-induced fission of {sup 233}U measured at Studsvik, the comparison of the OSIRIS and LOHENGRIN facilities and the trends in new data for the Reactors Physics have been discussed. (author)

Method of measurement of cross sections of heavy nuclei fission induced by intermediate energy protons

International Nuclear Information System (INIS)

Kotov, Alexander; Chtchetkovski, Alexander; Fedorov, Oleg; Gavrikov, Yuri; Chestnov, Yuri; Poliakov, Vladimir; Vaishnene, Larissa; Vovchenko, Vil; Fukahori, Tokio

2003-01-01

The purpose of this work is experimental studies of the energy dependence of the fission cross sections of heavy nuclei, nat Pb, 209 Bi, 232 Th, 233 U, 235 U, 238 U, 237 Np and 239 Pu, by protons at the energies from 200 to 1000 MeV. At present experiment the method based on use of the gas parallel plate avalanche counters (PPACs) for registration of complementary fission fragments in coincidence and the telescope of scintillation counters for direct counting of the incident protons on the target has been used. First preliminary results of the energy dependences of proton induced fission cross sections for nat Pb, 209 Bi, 235 U and 238 U are reported. (author)

Detection of fission signatures induced by a low-energy neutron source

International Nuclear Information System (INIS)

Ocherashvili, A.; Becka, A.; Mayorovb, V.; Roesgen, E.; Crochemoreb, J.-M.; Mosconi, M.; Pedersen, B.; Heger, C.

2015-01-01

We present a method for the detection of special nuclear materials (SNM) in shielded containers which is both sensitive and applicable under field conditions. The method uses an external pulsed neutron source to induce fission in SNM and subsequent detection of the fast prompt fission neutrons. The detectors surrounding the container under investigation are liquid scintillation detectors able to distinguish gamma rays from fast neutrons by means of the pulse shape discrimination method (PSD). One advantage of these detectors, besides the ability for PSD analysis, is that the analogue signal from a detection event is of very short duration (typically few tens of nanoseconds). This allows the use of very short coincidence gates for the detection of the prompt fission neutrons in multiple detectors while benefiting from a low accidental (background) coincidence rate yielding a low detection limit. Another principle advantage of this method derives from the fact that the external neutron source is pulsed. By proper time gating the interrogation can be conducted by epithermal and thermal source neutrons only. These source neutrons do not appear in the fast neutron signal following the PSD analysis thus providing a fundamental method for separating the interrogating source neutrons from the sample response in form of fast fission neutrons. The paper describes laboratory tests with a configuration of eight detectors in the Pulsed Neutron Interrogation Test Assembly (PUNITA). The sensitivity of the coincidence signal to fissile mass is investigated for different sample configurations and interrogation regimes.

Fission cross-section calculations and the multi-modal fission model

International Nuclear Information System (INIS)

Hambsch, F.J.

2004-01-01

New, self consistent, neutron-induced reaction cross section calculations for 235,238 U, 237 Np have been performed. The statistical model code STATIS was improved to take into account the multimodality of the fission process. The three most dominant fission modes, the two asymmetric standards I (S1) and standard II (S2) modes and the symmetric superlong (SL) mode have been taken into account. De-convoluted fission cross sections for those modes for 235,238 U(n,f) and 237 Np(n,f) based on experimental branching ratios, were calculated for the first time up to the second chance fission threshold. For 235 U(n,f), the calculations being made up to 28 MeV incident neutron energy, higher fission chances have been considered. This implied the need for additional calculations for the neighbouring isotopes. As a side product also mass yield distributions could be calculated at energies hitherto not accessible by experiment. Experimental validation of the predictions is being envisaged

Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome

Science.gov (United States)

McCarthy, Cameron G.; Szasz, Theodora; Goulopoulou, Styliani; Webb, R. Clinton

2015-01-01

Fifty percent of trauma patients who present sepsis-like syndrome do not have bacterial infections. This condition is known as systemic inflammatory response syndrome (SIRS). A unifying factor of SIRS and sepsis is cardiovascular collapse. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns. Mitochondrial N-formyl peptides (F-MIT) are damage-associated molecular patterns that share similarities with bacterial N-formylated peptides and are potent immune system activators. The goal of this study was to investigate whether F-MIT trigger SIRS, including hypotension and vascular collapse via formyl peptide receptor (FPR) activation. We evaluated cardiovascular parameters in Wistar rats treated with FPR or histamine receptor antagonists and inhibitors of the nitric oxide pathway before and after F-MIT infusion. F-MIT, but not nonformylated peptides or mitochondrial DNA, induced severe hypotension via FPR activation and nitric oxide and histamine release. Moreover, F-MIT infusion induced hyperthermia, blood clotting, and increased vascular permeability. To evaluate the role of leukocytes in F-MIT-induced hypotension, neutrophil, basophil, or mast cells were depleted. Depletion of basophils, but not neutrophils or mast cells, abolished F-MIT-induced hypotension. Rats that underwent hemorrhagic shock increased plasma levels of mitochondrial formylated proteins associated with lung damage and antagonism of FPR ameliorated hemorrhagic shock-induced lung injury. Finally, F-MIT induced vasodilatation in isolated resistance arteries via FPR activation; however, F-MIT impaired endothelium-dependent relaxation in the presence of blood. These data suggest that F-MIT may be the link among trauma, SIRS, and cardiovascular collapse. PMID:25637548

Setup for fission and evaporation cross-section measurements in reactions induced by secondary beams

International Nuclear Information System (INIS)

Hassan, A.A.; Luk'yanov, S.M.; Kalpakchieva, R.; Skobelev, N.K.; Penionzhkevich, Yu.Eh.; Dlouhy, Z.; Radnev, S.; Poroshin, N.V.

2002-01-01

A setup for studying reactions induced by secondary radioactive beams has been constructed. It allows simultaneous measurement of α-particle and fission fragment energy spectra. By measuring the α-particles, identification of evaporation residues is achieved. A set of three targets can be used so as to ensure sufficient statistics. Two silicon detectors, located at 90 degrees to the secondary beam direction, face each target, thus covering 30% of the solid angle. This experimental setup is to be used to obtain excitation functions of fusion-fission reactions and of reactions leading to evaporation residue production

Comparison Of ²⁵²Cf Time Correlated Induced Fisssion With AmLi Induced Fission On Fresh MTR Research Reactor Fuel

Energy Technology Data Exchange (ETDEWEB)

Joshi, Jay Prakash [Los Alamos National Laboratory

2017-03-30

The effective application of international safeguards to research reactors requires verification of spent fuel as well as fresh fuel. To accomplish this goal various nondestructive and destructive assay techniques have been developed in the US and around the world. The Advanced Experimental Fuel Counter (AEFC) is a nondestructive assay (NDA) system developed at Los Alamos National Laboratory (LANL) combining both neutron and gamma measurement capabilities. Since spent fuel assemblies are stored in water, the system was designed to be watertight to facilitate underwater measurements by inspectors. The AEFC is comprised of six ³He detectors as well as a shielded and collimated ion chamber. The ³He detectors are used for active and passive neutron coincidence counting while the ion chamber is used for gross gamma counting. Active coincidence measurement data is used to measure residual fissile mass, whereas the passive coincidence measurement data along with passive gamma measurement can provide information about burnup, cooling time, and initial enrichment. In the past, most of the active interrogation systems along with the AEFC used an AmLi neutron interrogation source. Owing to the difficulty in obtaining an AmLi source, a ²⁵²Cf spontaneous fission (SF) source was used during a 2014 field trail in Uzbekistan as an alternative. In this study, experiments were performed to calibrate the AEFC instrument and compare use of the ²⁵²Cf spontaneous fission source and the AmLi (α,n) neutron emission source. The ²⁵²Cf source spontaneously emits bursts of time-correlated prompt fission neutrons that thermalize in the water and induce fission in the fuel assembly. The induced fission (IF) neutrons are also time correlated resulting in more correlated neutron detections inside the ³He detector, which helps reduce the statistical errors in doubles when using the ²⁵²Cf interrogation source instead of

Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission.

Science.gov (United States)

Su, Bo; Ji, Yun-Song; Sun, Xu-lu; Liu, Xiang-Hua; Chen, Zhe-Yu

2014-01-17

Appropriate mitochondrial transport and distribution are essential for neurons because of the high energy and Ca(2+) buffering requirements at synapses. Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating synaptic transmission and plasticity. However, whether and how BDNF can regulate mitochondrial transport and distribution are still unclear. Here, we find that in cultured hippocampal neurons, application of BDNF for 15 min decreased the percentage of moving mitochondria in axons, a process dependent on the activation of the TrkB receptor and its downstream PI3K and phospholipase-Cγ signaling pathways. Moreover, the BDNF-induced mitochondrial stopping requires the activation of transient receptor potential canonical 3 and 6 (TRPC3 and TRPC6) channels and elevated intracellular Ca(2+) levels. The Ca(2+) sensor Miro1 plays an important role in this process. Finally, the BDNF-induced mitochondrial stopping leads to the accumulation of more mitochondria at presynaptic sites. Mutant Miro1 lacking the ability to bind Ca(2+) prevents BDNF-induced mitochondrial presynaptic accumulation and synaptic transmission, suggesting that Miro1-mediated mitochondrial motility is involved in BDNF-induced mitochondrial presynaptic docking and neurotransmission. Together, these data suggest that mitochondrial transport and distribution play essential roles in BDNF-mediated synaptic transmission.

Tempol, a Superoxide Dismutase Mimetic Agent, Ameliorates Cisplatin-Induced Nephrotoxicity through Alleviation of Mitochondrial Dysfunction in Mice

Science.gov (United States)

Ahmed, Lamiaa A.; Shehata, Nagwa I.; Abdelkader, Noha F.; Khattab, Mahmoud M.

2014-01-01

Background Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice. Methods and Findings Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg) with or without oral administration of tempol (100 mg/kg/day). Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP) content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I–IV activities and mitochondrial nitric oxide synthase (mNOS) protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma. Conclusion This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction

Proton-induced fission of actinides at energies 26.5 and 62.9 MeV--Theoretical interpretation

International Nuclear Information System (INIS)

Demetriou, P.; Keutgen, Th.; Prieels, R.; El Masri, Y.

2011-01-01

Fission properties of proton-induced fission on 232 Th, 237 Np, 238 U, 239 Pu and 241 Am targets, measured at the Louvain-la-Neuve cyclotron facility at proton energies of 26.5 and 62.9 MeV, are compared with the predictions of the state-of-the-art nuclear reaction code TALYS. The sensitivity of the calculations to the input parameters of the code and possible improvements are discussed.

Measurements of fission cross-sections and of neutron production rates; Mesures de sections efficaces de fission et du nombre de neutrons prompts emis par fission

Energy Technology Data Exchange (ETDEWEB)

Billaud, P; Clair, C; Gaudin, M; Genin, R; Joly, R; Leroy, J L; Michaudon, A; Ouvry, J; Signarbieux, C; Vendryes, G [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1958-07-01

a) Measurements of neutron induced fission cross-sections in the low energy region. The variation of the fission cross sections of several fissile isotopes has been measured and analysed, for neutron energies below 0,025 eV. The monochromator was a crystal spectrometer used in conjunction with a mechanical velocity selector removing higher order Bragg reflections. The fissile material was laid down on the plates of a fission chamber by painting technic. An ionization chamber, having its plates coated with thin {sup 10}B layers, was used as the neutron flux monitor. b) Measurement of the fission cross section of {sup 235}U. We intend to measure the variation of the neutron induced fission cross section of {sup 235}U over the neutron energy range from 1 keV by the time of flight method. The neutron source is the uranium target of a pulsed 28 MeV electron linear accelerator. The detector is a large fission chamber, with parallel plates, containing about 10 g of {sup 235}U (20 deposits of 25 cm diameter). The relative fission data were corrected for the neutron spectrum measured with a set of BF{sub 3} proportional counters. c) Mean number {nu} of neutrons emitted in neutron induced fission. We measured the value of {nu} for several fissile isotopes in the case of fission induced by 14 MeV neutrons. The 14 MeV neutrons were produced by D (t, n) {alpha} reaction by means of a 300 kV Cockcroft Walton generator. (author)Fren. [French] a) Mesures de sectionficaces de fission a basse energie. Nous avons mesure et analyse la variation de la section efficace de fission de divers isotopes fissiles pour des neutrons d'energie inferieure a 0,025 eV. Le monochromateur est constitue par un spectrometre a cristal auquel est associe un selecteur mecanique destine a eliminer les diffractions de Bragg d'ordre superieur au premier. Le materiau fissile est contenu dans une chambre a fission sous forme de depots realises par peinture; une chambre d'ionisation a depots minces de B{sub 10

Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

Directory of Open Access Journals (Sweden)

Richard de Boer

Full Text Available Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegans to study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase.

Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

Energy Technology Data Exchange (ETDEWEB)

Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Young Sang [College of Natural Sciences, Chungnam National University, Daejeon (Korea, Republic of)

2011-09-15

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated {beta}-galactosidase (SA-{beta}-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H{sub 2}O{sub 2}-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H{sub 2}O{sub 2}-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-{beta}-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

International Nuclear Information System (INIS)

Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee; Kim, Young Sang

2011-01-01

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated β-galactosidase (SA-β-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H 2 O 2 -treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H 2 O 2 -treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-β-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

Qing Dai attenuates nonsteroidal anti-inflammatory drug-induced mitochondrial reactive oxygen species in gastrointestinal epithelial cells.

Science.gov (United States)

Saito, Rie; Tamura, Masato; Matsui, Hirofumi; Nagano, Yumiko; Suzuki, Hideo; Kaneko, Tsuyoshi; Mizokami, Yuji; Hyodo, Ichinosuke

2015-01-01

Treatments with nonsteroidal anti-inflammatory drugs (NSAIDs) have increased the number of patients with gastrointestinal complications. Qing Dai has been traditionally used in Chinese herbal medicine for various inflammatory diseases such as ulcerative colitis. We previously reported that Qing Dai suppressed inflammations by scavenging reactive oxygen species (ROS) in ulcerative colitis patients. Thus, Qing Dai can attenuate the production of ROS, which play an important role in NSAID-induced gastrointestinal injuries. In this study, we aimed to elucidate whether Qing Dai decreased mitochondrial ROS production in NSAID-treated gastrointestinal cells by examining cellular injury, mitochondrial membrane potentials, and ROS production with specific fluorescent indicators. We also performed electron paramagnetic resonance measurement in isolated mitochondria with a spin-trapping reagent (CYPMPO or DMPO). Treatments with indomethacin and aspirin induced cellular injury and mitochondrial impairment in the gastrointestinal cells. Under these conditions, mitochondrial alterations were observed on electron microscopy. Qing Dai prevented these complications by suppressing ROS production in gastrointestinal cells. These results indicate that Qing Dai attenuated the ROS production from the NSAID-induced mitochondrial alteration in the gastrointestinal epithelial cells. Qing Dai treatment may be considered effective for the prevention NSAID-induced gastrointestinal injury.

Distribution of nuclear charge in the proton-induced fission of Th-232

Energy Technology Data Exchange (ETDEWEB)

Pate, B D [Brookhaven National Laboratory, Upton, New York (United States); Foster, J S; Yaffe, L [McGill Univ., Montreal, Quebec (Canada)

1958-09-15

A great deal of work has been done on the distribution of nuclear mass in the fission process. About the nuclear charge distribution less is known. Data exist on the distribution from the fission of U-235 with thermal neutrons and with 14 Mev neutrons. Data also exist for the fission of uranium by 170 Mev protons, of bismuth by 190 Mev deuterons, and of uranium, thorium and bismuth by 480 Mev protons, and there is fragmentary information from other systems. The present work was undertaken to investigate the changes that occur in the charge distribution from proton-induced fission of Th-232 as the bombarding energy is raised from 8 to 90 Mev, the maximum proton energy of the McGill synchrocyclotron. This energy range is of interest in view of the substantial changes observed in the mass distribution. Also in this interval a change presumably begins in the nature of the initial step in nuclear reactions, from simple compound-nucleus formation, to a mechanism of direct interaction with individual nucleons. Thus at the lower energies studied, excitation of the nuclei at the end of the first step of the reaction will be essentially monochromatic whereas at the higher end of the bombarding-energy range, a broad spectrum of excitation energies will be produced, with corresponding complexity of the reaction products observed. (author)

Characterisation of the nascent polypeptide-associated complex in fission yeast

DEFF Research Database (Denmark)

Andersen, Katrine M; Semple, Colin A; Hartmann-Petersen, Rasmus

2007-01-01

with other cell proteins, but has also been found to associate with DNA junctions, and to be involved in other processes including transcription regulation and mitochondrial protein import.Here, we characterize NAC in fission yeast. We find that NAC is associated with ribosomes, while a significant fraction...... defects in protein degradation. Accordingly, we find that the NAC UBA domain belongs to an ancient and distinct subgroup of the UBA family. In contrast to the situation with budding yeast, fission yeast cells devoid of NAC were not temperature sensitive. However, they displayed resistance to the amino...

The role of PGC-1α and MRP1 in lead-induced mitochondrial toxicity in testicular Sertoli cells

International Nuclear Information System (INIS)

Li, Zhen; Liu, Xi; Wang, Lu; Wang, Yan; Du, Chuang; Xu, Siyuan; Zhang, Yucheng; Wang, Chunhong; Yang, Chengfeng

2016-01-01

The lead-induced toxic effect on mitochondria in Sertoli cells is not well studied and the underlying mechanism is poorly understood. Here we reported the potential role of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and multidrug resistance protein 1 (MRP1) in lead acetate-induced mitochondrial toxicity in mouse testicular Sertoli cells TM4 line. We found that lead acetate treatment significantly reduced the expression level of PGC-1α, but increased the level of MRP1 in mitochondria of TM4 cells. To determine the role of PGC-1α and MRP1 in lead acetate-induced mitochondrial toxicity, we then generated PGC-1α stable overexpression and MRP1 stable knockdown TM4 cells, respectively. The lead acetate treatment caused TM4 cell mitochondrial ultrastructure damages, a decrease in ATP synthesis, an increase in ROS levels, and apoptotic cell death. In contrast, stably overexpressing PGC-1α significantly ameliorated the lead acetate treatment-caused mitochondrial toxicity and apoptosis. Moreover, it was also found that stably knocking down the level of MRP1 increased the TM4 cell mitochondrial lead-accumulation by 4–6 folds. Together, the findings from this study suggest that PGC-1α and MRP1 plays important roles in protecting TM4 cells against lead-induced mitochondrial toxicity, providing a better understanding of lead-induced mitochondrial toxicity.

Energies and Yields of Prompt Gamma Rays from Fragments in Slow-Neutron Induced Fission of 235U

Energy Technology Data Exchange (ETDEWEB)

Albinsson, H [Chalmers Univ. of Technology, Goeteborg (SE)

1971-04-15

Measurements were made on the gamma radiation emitted from fission fragments in slow-neutron induced fission of 235U. The fragments were detected with solid state detectors of the surface barrier type and the gamma radiation with a Nal(Tl) scintillator. Mass selection was used so that the gamma radiation could be measured as a function of fragment mass. Time discrimination between the fission gammas and the prompt neutrons released in the fission process was employed to reduce the background. The gamma radiation emitted during different time intervals after the fission event was studied with the help of a collimator, the position of which was changed along the path of the fission fragments. In this way it was possible to select various collimator settings and let gamma radiation of different half-lives be enhanced. Gamma-ray energy spectra from these time components were then recorded as function of mass. The spectrum shape differed greatly depending on the half-life of the radiation and the fragment from which it was emitted. The results of the present measurements were discussed in the light of existing fission models, and comparisons were made with prompt gamma-ray and neutron data from other fission experiments

Energies and Yields of Prompt Gamma Rays from Fragments in Slow-Neutron Induced Fission of 235U

International Nuclear Information System (INIS)

Albinsson, H.

1971-04-01

Measurements were made on the gamma radiation emitted from fission fragments in slow-neutron induced fission of 235 U. The fragments were detected with solid state detectors of the surface barrier type and the gamma radiation with a Nal(Tl) scintillator. Mass selection was used so that the gamma radiation could be measured as a function of fragment mass. Time discrimination between the fission gammas and the prompt neutrons released in the fission process was employed to reduce the background. The gamma radiation emitted during different time intervals after the fission event was studied with the help of a collimator, the position of which was changed along the path of the fission fragments. In this way it was possible to select various collimator settings and let gamma radiation of different half-lives be enhanced. Gamma-ray energy spectra from these time components were then recorded as function of mass. The spectrum shape differed greatly depending on the half-life of the radiation and the fragment from which it was emitted. The results of the present measurements were discussed in the light of existing fission models, and comparisons were made with prompt gamma-ray and neutron data from other fission experiments

Maternal aging affects oocyte resilience to carbonyl cyanide-m-chlorophenylhydrazone -induced mitochondrial dysfunction in cows.

Directory of Open Access Journals (Sweden)

Kazuki Kansaku

Full Text Available Mitochondrial quality control is important for maintaining cellular and oocyte viability. In addition, aging affects mitochondrial quality in many cell types. In the present study, we examined how aging affects oocyte mitochondrial biogenesis and degeneration in response to induced mitochondrial dysfunction. Cumulus oocyte complexes were harvested from the ovaries of young (21‒45 months and aged (≥120 months cows and treated for 2 hours with 10 μM carbonyl cyanide-m- chlorophenylhydrazone (CCCP, or a vehicle control, after which cumulus oocyte complexes were subjected to in vitro fertilization and culture. CCCP treatment reduced ATP content and increased reactive oxygen species (ROS levels in the oocytes of both young and aged cows. When CCCP-treated cumulus oocyte complexes were subsequently cultured for 19 hours and/or subjected to fertilization, high ROS levels in oocytes and a low rate of blastocyst development was observed in oocytes derived from aged cows. In addition, we observed differential responses in mitochondrial biogenesis to CCCP treatment between young and aged cows. CCCP treatment enhanced mitochondrial biogenesis concomitant with upregulation of SIRT1 expression in oocytes of young, but not aged, cows. In conclusion, aging affects mitochondrial quality control and recuperation of oocytes following CCCP-induced mitochondrial dysfunction.

Two reports: (i) Correlation properties of delayed neutrons from fast neutron induced fission. (ii) Method and set-up for measurements of trace level content of heavy fissionable elements based on delayed neutron counting

International Nuclear Information System (INIS)

Piksaikin, V.M.; Isaev, S.G.; Goverdovski, A.A.; Pshakin, G.M.

1998-10-01

The document includes the following two reports: 'Correlation properties of delayed neutrons from fast neutron induced fission' and 'Method and set-up for measurements of trace level content of heavy fissionable elements based on delayed neutron counting. A separate abstract was prepared for each report

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis

International Nuclear Information System (INIS)

Wang, Lai; Chen, Man; Yuan, Lin; Xiang, Yuting; Zheng, Ruimao; Zhu, Shigong

2014-01-01

Highlights: • 14,15-EET inhibits OGD-induced apoptosis in cortical neurons. • Mitochondrial biogenesis of cortical neurons is promoted by 14,15-EET. • 14,15-EET preserves mitochondrial function of cortical neurons under OGD. • CREB mediates effect of 14,15-EET on mitochondrial biogenesis and function. - Abstract: 14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen–glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Wang, Lai; Chen, Man; Yuan, Lin; Xiang, Yuting [Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China); Zheng, Ruimao, E-mail: rmzheng@pku.edu.cn [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China); Zhu, Shigong, E-mail: sgzhu@bjmu.edu.cn [Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China)

2014-07-18

Highlights: • 14,15-EET inhibits OGD-induced apoptosis in cortical neurons. • Mitochondrial biogenesis of cortical neurons is promoted by 14,15-EET. • 14,15-EET preserves mitochondrial function of cortical neurons under OGD. • CREB mediates effect of 14,15-EET on mitochondrial biogenesis and function. - Abstract: 14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen–glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1.

Neutron gamma competition in fast fission

International Nuclear Information System (INIS)

Frehaut, J.

1989-01-01

In the present paper we analyse the data we have obtained on the distribution of the gamma-ray energy per fission, as well as on the average energy E-barγ released per fission for the neutron induced fission of several isotopes, in the energy range up to 15 MeV. 6 refs, 9 figs

Angular distribution of gamma rays from the fission of {sup 235}U induced by 14-MeV neutrons

Energy Technology Data Exchange (ETDEWEB)

Jeki, L; Kluge, G; Lajtai, A [Central Research Institute for Physics, Hungarian Academy of Sciences (Hungary)

1969-12-15

Experiments are reported which were performed to study the angular distribution of the gamma radiation following fast-neutron-induced nuclear fission. The investigations were, in particular, focussed on the influence which the angular momentum imparted to the compound nucleus by the fast neutrons has on the angular distribution of the {gamma}-rays. The fission of {sup 235}U is induced by 14-MeV-energy neutrons from the T(d, n) {alpha} reaction. The fission fragments are detected by a gas-scintillation counter filled with a mixture of Ar and Ni gases, the {gamma}-rays by 5 cm x 5 cm Nal(Tl) crystal with an energy threshold of 120 keV. The intensity of the {gamma}-rays is measured at 90 deg. and 174 deg. to the direction of fragment motion. The flight times of fission neutrons and {gamma}-rays are measured with a 20-ns overlap-type time-to-pulse height converter while the background was covered simultaneously with another converter delayed with respect to the former. The signals from both converters are analysed by a multichannel analyser with divisible memory. The flight path, which is chosen to be about 70 cm, makes it possible to separate the neutron from the gamma counts. The geometry is designed to keep the direction of the outflying fission fragments nearly the same as that of the incident fast neutrons. In this way the angular momenta of the fast neutrons are normal to the flight path of the fragments. The measured gamma intensities are extrapolated to 180 deg on a computer using Strutinski's formula n({theta}) {approx} 1 + B sin {theta}. On transformation of the measured data from the laboratory system to the system of fragments the anisotropy is found to be A = I(180 deg.)/I (90 deg.) = 1.33 {+-} 0.05. The main angular momentum of fission fragments is calculated from the anisotropy as 15 (h/2{pi}) units. As compared with the thermal-neutron-induced fission the present results indicate an additional contribution from the angular momentum of the compound

GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction.

Directory of Open Access Journals (Sweden)

Raquel Montero

Full Text Available We previously described increased levels of growth and differentiation factor 15 (GDF-15 in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21. To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction.We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA.Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM relative to healthy (350, 21 and myopathic (350, 32 controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4% and 92.3% (81.5%-97.9%, respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated.Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

Directory of Open Access Journals (Sweden)

Magdalena Cristóbal-García

2015-01-01

Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

Lost region in amyloid precursor protein (APP) through TALEN-mediated genome editing alters mitochondrial morphology.

Science.gov (United States)

Wang, Yajie; Wu, Fengyi; Pan, Haining; Zheng, Wenzhong; Feng, Chi; Wang, Yunfu; Deng, Zixin; Wang, Lianrong; Luo, Jie; Chen, Shi

2016-02-29

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) deposition in the brain. Aβ plaques are produced through sequential β/γ cleavage of amyloid precursor protein (APP), of which there are three main APP isoforms: APP695, APP751 and APP770. KPI-APPs (APP751 and APP770) are known to be elevated in AD, but the reason remains unclear. Transcription activator-like (TAL) effector nucleases (TALENs) induce mutations with high efficiency at specific genomic loci, and it is thus possible to knock out specific regions using TALENs. In this study, we designed and expressed TALENs specific for the C-terminus of APP in HeLa cells, in which KPI-APPs are predominantly expressed. The KPI-APP mutants lack a 12-aa region that encompasses a 5-aa trans-membrane (TM) region and 7-aa juxta-membrane (JM) region. The mutated KPI-APPs exhibited decreased mitochondrial localization. In addition, mitochondrial morphology was altered, resulting in an increase in spherical mitochondria in the mutant cells through the disruption of the balance between fission and fusion. Mitochondrial dysfunction, including decreased ATP levels, disrupted mitochondrial membrane potential, increased ROS generation and impaired mitochondrial dehydrogenase activity, was also found. These results suggest that specific regions of KPI-APPs are important for mitochondrial localization and function.

Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis

International Nuclear Information System (INIS)

Wu, C.-W.; Ping, Y.-H.; Yen, J.-C.; Chang, C.-Y.; Wang, S.-F.; Yeh, C.-L.; Chi, C.-W.; Lee, H.-C.

2007-01-01

Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in Brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects