factor-2 kinase-mediated autophagy: Topics by WorldWideScience.org

The multiple roles of autophagy in cancer

Autophagy is an evolutionarily conserved catabolic process that involves the invagination and degradation of cytoplasmic components through an autophagosomelysosome track. Autophagy functions...Full Text Available

2010-12-01

The IKK complex contributes to the induction of autophagy

Autophagy is an evolutionarily conserved, catabolic process that involves the entrapment of cytoplasmic components within characteristic vesicles for their delivery to and degradation within lysosomes....Full Text Available

2011-07-01

Picornavirus Subversion of the Autophagy Pathway

In response to stress, cells start transcriptional and transcription-independent programs that can lead to adaptation or death. Here, we show that multiple inducers of autophagy, including nutrient...Full Text Available

2010-02-03

When autophagy meets viruses: a double-edged sword with functions in defense and offense

While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates...Full Text Available

Synthetic substrates for measuring activity of autophagy proteases

Autophagy is a ubiquitous catabolic process that ensures organism’s well-being by sequestering a wide array of undesired intracellular constituents into double-membrane vesicles termed...Full Text Available

2010-12-01

Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy

Atg4 cysteine proteases (autophagins) play crucial roles in autophagy by proteolytic activation of Atg8 paralogs for targeting to autophagic vesicles by lipid conjugation, as well as in subsequent deconjugation...Full Text Available

2010-10-01

Autophosphorylation Within the Atg1 Activation Loop Is Required for Both Kinase Activity and the Induction of Autophagy in Saccharomyces cerevisiae

Atg9 is a transmembrane protein essential for autophagy which cycles between the Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells during starvation through a mechanism...Full Text Available

2011-01-01

The EGFR antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1? and Bcl-2 and activating the beclin-1/hVps34 complex

Autophagy is an evolutionarily conserved degradative pathway that has been implicated in a number of physiological events important for human health. This process was originally identified as a response...Full Text Available

2010-07-01

Autophagy is a regulated catabolic process triggered in cells deprived of nutrients or growth factors that govern nutrient uptake. Here we report that autophagy is induced by cetuximab, a therapeutic...Full Text Available

2010-07-15

The Autophagy Connection

FoxO, Autophagy, and Cardiac Remodeling

For a process intimately connected to an immense range of physiological processes, the molecular understanding of macroautophagy remains far from complete. Recent large-scale studies, including...Full Text Available

2010-07-20

PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast

In response to changes in workload, the heart grows or shrinks. Indeed, the myocardium is capable of robust and rapid structural remodeling. In the setting of normal, physiological demand, the...Full Text Available

2010-08-01

Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model

Eukaryotic cells can massively transport their own cytoplasmic contents into a lytic compartment, the vacuole/lysosome, for recycling through a conserved system called autophagy. The key process in...Full Text Available

2011-01-01

British Library Electronic Table of Contents (United Kingdom)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...

2011-01-01

Exit from the Golgi Is Required for the Expansion of the Autophagosomal Phagophore in Yeast Saccharomyces cerevisiae

Cathepsin B facilitates Autophagy mediated apoptosis in SPARC Overexpressed Primitive Neuroectodermal Tumor cells

The delivery of proteins and organelles to the vacuole by autophagy involves membrane rearrangements that result in the formation of large vesicles called autophagosomes. The mechanism underlying autophagosome...Full Text Available

2010-07-01

ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death

Medulloblastoma and neuroblastoma belong to a group of neoplasms designated as primitive neuroectodermal tumors (PNETs). Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matrix-associated...Full Text Available

2010-10-01

A Master Conductor for Aggregate Clearance by Autophagy

SUMMARYATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as...Full Text Available

2010-08-20

The ATG1/ATG13 Protein Kinase Complex Is Both a Regulator and a Target of Autophagic Recycling in Arabidopsis.

Autophagic adapters including p62/SQSTM1 recognize polyubiquitinated autophagic targets such as toxic protein aggregates. Recently reporting in Molecular Cell, Filimonenko et al. provide evidence...Full Text Available

2010-05-18

Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation

Autophagy is an intracellular recycling route in eukaryotes whereby organelles and cytoplasm are sequestered in vesicles, which are subsequently delivered to the vacuole for breakdown. The process is induced by various nutrient-responsive signaling cascades converging on the Autophagy-Related1 (ATG1)/ATG13 kinase complex. Here, we describe the ATG1/13 complex in Arabidopsis thaliana and show that it is both a regulator and a target of autophagy. Plants missing ATG13 are hypersensitive to nutrient limitations and senesce prematurely similar to mutants lacking other components of the ATG system. Synthesis of the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts, which are essential for autophagy, still occurs in ATG13-deficient plants, but the biogenesis of ATG8-decorated autophagic bodies does not, indicating that the complex regulates downstream events required for autophagosome enclosure and/or ...

2011-10-01

British Library Electronic Table of Contents (United Kingdom)

Colorectal cancer is the second most common cause of cancer death in the world and about half of the patients with colorectal cancer require adjuvant therapy after surgical resection. Therefore, the eradication of cancer cells via chemotherapy constitutes a viable approach to treating patients with colorectal cancer. In this study, the effects of bufalin isolated from a traditional Chinese medicine were evaluated and characterized in HT-29 and Caco-2 human colon cancer cells. Contrary to its well-documented apoptosis-promoting activity in other cancer cells, bufalin did not cause caspase-dependent cell death in colon cancer cells, as indicated by the absence of significant early apoptosis as well as poly(ADP-ribose) polymerase and caspase-3 cleavage. Instead, bufalin activated an autophagy...

2011-01-01

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Age at onset in Huntington?s disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7

British Library Electronic Table of Contents (United Kingdom)

Huntington?s disease (HD) is caused by an expansion of a polyglutamine repeat of more than 35?units in the huntingtin protein. The expanded repeat length is inversely correlated with the age at onset (AAO); however, additional genetic factors apart from the expanded CAG repeat length can modify the course and the AAO in HD. Aberrations in macroautophagy have been observed in Huntington, Alzheimer, Parkinson, motor neuron and prion diseases. Therefore, we hypothesized that polymorphisms in autophagy-related (Atg) genes might contribute to the variation in the AAO. We initially tested eight single nucleotide polymorphisms in five Atg genes (Atg3, Atg5, Atg7, Atg16L1 and Beclin-1) for their frequency of ?1%. Subsequently, we investigated the polymorphisms Atg7 V471A and Atg16L1 T281A for a di...

2010-01-01

Eating the enemy in Crohn's disease

British Library Electronic Table of Contents (United Kingdom)

Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adhere...

2010-01-01

Assessment of GABARAP self-association by its diffusion properties

Energy Technology Data Exchange (ETDEWEB)

Gamma-aminobutyric acid type A receptor-associated protein (GABARAP) belongs to a family of small ubiquitin-like adaptor proteins implicated in intracellular vesicle trafficking and autophagy. We have used diffusion-ordered nuclear magnetic resonance spectroscopy to study the temperature and concentration dependence of the diffusion properties of GABARAP. Our data suggest the presence of distinct conformational states and provide support for self-association of GABARAP molecules. Assuming a monomer-dimer equilibrium, a temperature-dependent dissociation constant could be derived. Based on a temperature series of {sup 1}H{sup 15}N heteronuclear single quantum coherence nuclear magnetic resonance spectra, we propose residues potentially involved in GABARAP self-interaction. The possible biological significance of these observations is discussed with respect to alternative scenarios of oligomerization.

2010-09-15

Unconventional Secretion of AcbA in Dictyostelium discoideum through a Vesicular Intermediate?

Prolactin Receptor Signaling Is Essential for Perinatal Brown Adipocyte Function: A Role for Insulin-like Growth Factor-2

The acyl coenzyme A (CoA) binding protein AcbA is secreted unconventionally and processed into spore differentiation factor 2 (SDF-2), a peptide that coordinates sporulation in Dictyostelium...Full Text Available

2010-07-01

Dual Roles of Nrf2 in Cancer

BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available

ATM-Dependent Phosphorylation of ATF2 Is Required for the DNA Damage Response

In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing...Full Text Available

2008-01-01

Regulation of cell proliferation and apoptosis in neuroblastoma cells by ccp1, a FGF2 downstream gene

SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available

2005-05-27

Olfactomedin 4 suppresses prostate cancer cell growth and metastasis via negative interaction with cathepsin D and SDF-1.

BackgroundCoiled-coil domain containing 115 (Ccdc115) or coiled coil protein-1 (ccp1) was previously identified as a downstream gene of Fibroblast Growth Factor 2 (FGF2) highly expressed...Full Text Available

Feature extraction for rolling element bearing fault diagnosis utilizing generalized S transform and two-dimensional non-negative matrix factorization

The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through regulating cell ...

2011-04-05

The protective role of ceramic filters against natural radioactivity of water

This paper presents a novel feature extraction scheme for roller bearing fault diagnosis utilizing generalized S transform and two-dimensional non-negative matrix factorization (2DNMF). The generalized S transform, which can make up the poor energy concentration of the standard S transform, is introduced to generate the time-frequency representation (TFR). Experiment results on simulated signal and vibration signals measured from rolling element bearings have revealed that the generalized S transform can obtain a more satisfactory TFR than other similar techniques. Furthermore, a new technique called two-dimensional non-negative matrix factorization (2DNMF), which can reduce the computation cost and preserve more structure information hiding in original 2D matrices compared to the NMF, is developed to extract more informative features from the time-frequency matrixes for accurate fault classification. ...

2011-05-01

The Significance of PITX2 Overexpression in Human Colorectal Cancer

The paper presents results of measurements of the natural radioactivity of tap water where samples were taken in front of, and behind the ceramic filter commonly used in houses for the purification of tap water. Altogether, 289 samples were taken, processed and measured during 1985-1986 in Kuwait. Results reveal the fact that ceramic filters reduce substantially the natural radioactivity in water (the 'gross' alpha activity reduced by the factor 2.18 #+-# 18%; the 'gross' beta by 1.53 #+-# 1.6%. (author).

British Library Electronic Table of Contents (United Kingdom)

Purpose The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancer...

2011-01-01

Relativistic r-modes and Shear viscosity: regularizing the continuous spectrum

CERN Document Server

Within a fully relativistic framework, we derive and solve numerically the perturbation equations of relativistic stars, including the stresses produced by a non-vanishing shear viscosity in the stress-energy tensor. With this approach, the real and imaginary parts of the frequency of the modes are consistently obtained. We find that, approaching the inviscid limit from the finite viscosity case, the continuous spectrum is regularized and we can calculate the quasi-normal modes for stellar models that do not admit solutions at first order in perturbation theory when the coupling between the polar and axial perturbations is neglected. The viscous damping time is found to agree within factor 2 with the usual estimate obtained by using the eigenfunctions of the inviscid limit and some approximation for the energy dissipation integrals. We find that the frequencies and viscous damping times for relativistic $r-$modes lie between the Newtonian and ...

2005-01-01

Regional assessment of ambient volatile organic compounds from biopharmaceutical R&D complex

British Library Electronic Table of Contents (United Kingdom)

Biopharmaceutical R&D complexes are major emission sources of volatile organic compounds (VOCs), which may pose potential health risks for staff on site and residents nearby. In this paper health risk assessments were performed for the VOCs in the ambient air of a typical biopharmaceutical R&D complex in China. Results showed halogenated and alkyl compounds were dominant components among 24 major VOCs from 9 selected sampling sites, inside or around the complex. The principal component analysis (PCA) indicated VOCs were generated predominantly from the biopharmaceutical research activities (factor 1 (F1), 71.6%) and traffic vehicles (factor 2 (F2), 15.4%), which were confirmed by contour maps of five selected VOCs (benzene, toluene, chlorobenzene, methylene chloride and n-hexane) simulated...

2011-01-01

Noise in Josephson mm-wave mixers

Poncirin promotes osteoblast differentiation but inhibits adipocyte differentiation in mesenchymal stem cells.

Point contact Josephson junctions can function as millimeter wave heterodyne mixers with conversion gain. The best results achieved thus far show a single sideband conversion gain of 1.3 and a mixer contribution to the system noise temperature of 54"0K. Both of these results are approximately 5 times better than the best published figures for cooled Schottky barrier diode mixers operated at the same frequency. The measured noise for a variety of junctions can be expressed as a universal function of the normalized rf frequency #OMEGA# = h#omega#/2eI/sub c/R. It is about a factor 2 larger than the calculated noise arising from the thermal noise in the junction shunt resistance, R. The noise calculation was done for the resistively shunted junction model using an analog junction simulator.

1974-09-30

Monte-Carlo-based simulation of LWR cores with innovative fuel concepts

Poncirin, flavanone glycoside, isolated from the fruit of Poncirus trifoliata, has anti-bacterial and anti-inflammatory activities. In this study, the effects of poncirin on the differentiation of mesenchymal stem cells were investigated. The C3H10T1/2 mesenchymal stem cells and primary bone marrow mesenchymal stem cells were studied. In the C3H10T1/2 cells, poncirin prevented adipocyte differentiation, as demonstrated by inhibition of cytoplasm lipid droplet accumulation and peroxisome proliferator-activating receptor-? (PPAR-?) and CCAAT-enhancer-binding protein-? (C/EBP-?) mRNA expression. By contrast, poncirin enhanced the expression of the key osteogenic transcription factors, runt-related transcription factor 2 (Runx2) and transcriptional coactivator with PDZ-binding motif (TAZ). Poncirin also enhanced expression of the osteogenic marker genes including alkaline phosphatase (ALP) and osteocalcin (OC). Poncirin increased mineral nodule ...

2011-05-01

Evolution of a molecular switch: universal bacterial GTPases regulate ribosome function.

High resolution Monte-Carlo simulations show that the neutron spectrum, fuel burnup and fuel temperature feedback effect of a PWR core loaded with Thoria-based fuel (Th/Pu-O_2) do not significantly differ from the MOX fuelled one due to the similar neutronic characteristics of both fertile materials (Th-232, U-238). The core physics of this fuel variant is characterized by an enhanced moderator/void temperature coefficient (by factor 2.4) and high incineration rate for Pu (approx. 60 %). A PWR core loaded with the Molybdenum-based inert matrix fuel (IMF) - in contrast to MOX-, shows a harder spectrum, resulting in small temperature coefficients of reactivity and particularly in a higher fuel depletion rate as well as an enhanced TRU reduction performance. The incineration of Pu amounts to 46 % resulting, in turn, in generation of minor actinides of about 10 % of the total Pu consumption. The higher excess reactivity resulting from the initial ...

2009-05-03

Dielectric properties of fluxed barium titanate ceramics with zirconia additions

The GTPases comprise a protein superfamily of highly conserved molecular switches adapted to many diverse functions. These proteins are found in all domains of life and often perform essential roles in fundamental cellular processes. Analysis of data from genome sequencing projects demonstrates that bacteria possess a core of 11 universally conserved GTPases (elongation factor G and Tu, initiation factor 2, LepA, Era, Obg, ThdF/TrmE, Ffh, FtsY, EngA and YchF). Investigations aimed at understanding the function of GTPases indicate that a second conserved feature of these proteins is that they elicit their function through interaction with RNA and/or ribosomes. An emerging concept suggests that the 11 universal GTPases are either necessary for ribosome function or transmitting information from the ribosome to downstream targets for the purpose of generating specific cellular responses. Furthermore, it is suggested that progenitor GTPases were ...

2001-07-01

Angiogenic cytokines and growth factors in systemic sclerosis.

BaTiO_3 compacts, when fluxed with < 2 vol% of a complex borate glass phase, were sintered to near theoretical density at temperatures < 1175 degrees C in 2 h. Microstructural analysis showed a uniform grain size < 1.0 #mu#m with 0.75 wt% ZrO_2 added to the flux phase as a grain growth inhibitor. TEM analysis revealed a microcrystalline grain-boundary phase with the ZrO_2 resident along the grain boundaries. These samples displayed an essentially flat dielectric profile, low dissipation factors (< 2%) over the range 25 degrees to 125 degrees C, a near linear dependence (#approx# #+-# 15%) between 25 degrees and - 55 degrees C, and significantly increased voltage stability. X-ray diffraction analysis of these small-grained materials indicates a suppression of the tetragonal structure toward a more cubic modification.

#gamma##gamma# Cross-sections and #gamma##gamma# colliders

Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin 1 (Ang-1), stromal cell-derived factor 1 (SDF-1/CXCL12), endothelin-1 (ET-1), monocyte chemoattractant ...

2011-04-28

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{gamma}{gamma} Cross-sections and {gamma}{gamma} colliders

We summarize the predictions of different models for total #gamma##gamma# cross-sections. The experimentally observed rise of #sigma#_#gamma#_#gamma# with s radical _#gamma#_#gamma#, faster than that for #sigma#_p_-_b_a_r_p, #sigma#_#gamma#_p is in agreement with the predictions of the Eikonalized Minijet Models as opposed to those of the Regge-Pomeron models. We then show that a measurement of #sigma#_#gamma#_#gamma# with an accuracy of < or approx. 8-9% (6-7%) is necessary to distinguish among different Regge-Pomeron type models (the different parameterisations of the EMM models) and a precision of < or approx. 20% is required to distinguish the predictions of the EMMs and of those models which treat 'photon like a proton', for the energy range 300< s radical_#gamma#_#gamma# <500 GeV. We further show that the difference in model predictions for #sigma#_#gamma#_#gamma# of about a factor 2 at s radical _#gamma#_#gamma# = 700 GeV ...

2001-10-11

Energy Technology Data Exchange (ETDEWEB)

We summarize the predictions of different models for total {gamma}{gamma} cross-sections. The experimentally observed rise of {sigma}{sub {gamma}}{sub {gamma}} with s radical {sub {gamma}}{sub {gamma}}, faster than that for {sigma}{sub p-barp}, {sigma}{sub {gamma}}{sub p} is in agreement with the predictions of the Eikonalized Minijet Models as opposed to those of the Regge-Pomeron models. We then show that a measurement of {sigma}{sub {gamma}}{sub {gamma}} with an accuracy of < or approx. 8-9% (6-7%) is necessary to distinguish among different Regge-Pomeron type models (the different parameterisations of the EMM models) and a precision of < or approx. 20% is required to distinguish the predictions of the EMMs and of those models which treat 'photon like a proton', for the energy range 300< s radical{sub {gamma}}{sub {gamma}} <500 GeV. We further show that the difference in model predictions for {sigma}{sub {gamma}}{sub {gamma}} of about a ...

2001-10-11

Structural Insights into the Interaction of the Evolutionarily Conserved ZPR1 Domain Tandem with Eukaryotic EF1A, Receptors, and SMN Complexes

Energy Technology Data Exchange (ETDEWEB)

Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and ...

2007-01-01

Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity

Land And Water Use Characteristics And Human Health Input Parameters For Use In Environmental Dosimetry And Risk Assessments At The Savannah River Site

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 ...

2008-05-01