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Sample records for calpain inhibitor ak

  1. Rational Design of Calpain Inhibitors Based on Calpastatin Peptidomimetics.

    Science.gov (United States)

    Low, Kristin E; Ler, Spencer; Chen, Kevin J; Campbell, Robert L; Hickey, Jennifer L; Tan, Joanne; Scully, Conor C G; Davies, Peter L; Yudin, Andrei K; Zaretsky, Serge

    2016-06-01

    Our previously reported structures of calpain bound to its endogenous inhibitor calpastatin have motivated the use of aziridine aldehyde-mediated peptide macrocyclization toward the design of cyclic peptides and peptidomimetics as calpain inhibitors. Inspired by nature's hint that a β-turn loop within calpastatin forms a broad interaction around calpain's active site cysteine, we have constructed and tested a library of 45 peptidic compounds based on this loop sequence. Four molecules have shown reproducibly low micromolar inhibition of calpain-2. Further systematic sequence changes led to the development of probes that displayed increased potency and specificity of inhibition against calpain over other cysteine proteases. Calculated Ki values were in the low micromolar range, rivaling other peptidomimetic calpain inhibitors and presenting an improved selectivity profile against other therapeutically relevant proteases. Competitive and mixed inhibition against calpain-2 was observed, and an allosteric inhibition site on the enzyme was identified for a noncompetitive inhibitor. PMID:27148623

  2. Calpain inhibitor nanocrystals prepared using Nano Spray Dryer B-90

    OpenAIRE

    Baba, Koichi; Nishida, Kohji

    2012-01-01

    The Nano Spray Dryer B-90 offers a new, simple, and alternative approach for the production of drug nanocrystals. Among attractive drugs, calpain inhibitor that inhibits programmed cell death ‘apoptosis’ is a candidate for curing apoptosis-mediated intractable diseases such as Alzheimer’s disease and Parkinson’s disease. In this study, the preparation of calpain inhibitor nanocrystals using Nano Spray Dryer B-90 was demonstrated. The particle sizes were controlled by means of selecting mesh a...

  3. Calpain inhibitor nanocrystals prepared using Nano Spray Dryer B-90

    Science.gov (United States)

    Baba, Koichi; Nishida, Kohji

    2012-08-01

    The Nano Spray Dryer B-90 offers a new, simple, and alternative approach for the production of drug nanocrystals. Among attractive drugs, calpain inhibitor that inhibits programmed cell death `apoptosis' is a candidate for curing apoptosis-mediated intractable diseases such as Alzheimer's disease and Parkinson's disease. In this study, the preparation of calpain inhibitor nanocrystals using Nano Spray Dryer B-90 was demonstrated. The particle sizes were controlled by means of selecting mesh aperture sizes. The obtained average particle sizes were in the range of around 300 nm to submicron meter.

  4. Effect of Calpain inhibitor I on glucocorticoid receptor-dependent degradation and its transactivation ability

    Institute of Scientific and Technical Information of China (English)

    程晓刚; 粟永萍; 罗成基; 刘晓宏

    2004-01-01

    Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocoaicoid receptor, and enhances glucocorticoid receptor transactivation ability.

  5. Mechanism of Action of Thalassospiramides, A New Class of Calpain Inhibitors

    KAUST Repository

    Lu, Liang

    2015-03-05

    Thalassospiramides comprise a large family of lipopeptide natural products produced by Thalassospira and Tistrella marine bacteria. Here we provide further evidence of their nanomolar inhibitory activity against the human calpain 1 protease. Analysis of structure-activity relationship data supported our hypothesis that the rigid 12-membered ring containing an α,β-unsaturated carbonyl moiety is the pharmacologically active functional group, in contrast to classic electrophilic "warheads" in known calpain inhibitors. Using a combination of chemical modifications, mass spectrometric techniques, site-directed mutagenesis, and molecular modeling, we show the covalent binding of thalassospiramide\\'s α,β-unsaturated carbonyl moiety to the thiol group of calpain\\'s catalytic Cys115 residue by a Michael 1,4-addition reaction. As nanomolar calpain inhibitors with promising selectivity and low toxicity from natural sources are rare, we consider thalassospiramides as promising drug leads.

  6. Cocrystal Structures of Primed Side-Extending α-Ketoamide Inhibitors Reveal Novel Calpain-Inhibitor Aromatic Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Qian,J.; Cuerrier, D.; Davies, P.; Li, Z.; Powers, J.; Campbell, R.

    2008-01-01

    Calpains are intracellular cysteine proteases that catalyze the cleavage of target proteins in response to Ca2+ signaling. When Ca2+ homeostasis is disrupted, calpain overactivation causes unregulated proteolysis, which can contribute to diseases such as postischemic injury and cataract formation. Potent calpain inhibitors exist, but of these many cross-react with other cysteine proteases and will need modification to specifically target calpain. Here, we present crystal structures of rat calpain 1 protease core ({mu}I-II) bound to two a-ketoamide-based calpain inhibitors containing adenyl and piperazyl primed-side extensions. An unexpected aromatic-stacking interaction is observed between the primed-side adenine moiety and the Trp298 side chain. This interaction increased the potency of the inhibitor toward {mu}I-II and heterodimeric m-calpain. Moreover, stacking orients the adenine such that it can be used as a scaffold for designing novel primed-side address regions, which could be incorporated into future inhibitors to enhance their calpain specificity.

  7. Effects of inhibitors on the synergistic interaction between calpain and caspase-3 during post-mortem aging of chicken meat.

    Science.gov (United States)

    Chen, Lin; Feng, Xian Chao; Zhang, Wan Gang; Xu, Xing Lian; Zhou, Guang Hong

    2012-08-29

    Calpain has been considered to be the most important protease involved in tenderization during the conversion of muscle into meat. However, recent evidence suggests the possible involvement of the key apoptosis protease, caspase, on post-mortem tenderization. This study used inhibitors of calpain and caspase-3 to treat chicken muscle immediately after slaughter and followed the changes in caspase-3 and calpain activities together with their expression during 5 days of aging. Addition of calpain inhibitors to the system resulted in significantly higher caspase-3 activities (p tenderizing process during the conversion of muscle tissue into meat. PMID:22720745

  8. Calpastatin exon 1B-derived peptide, a selective inhibitor of calpain: enhancing cell permeability by conjugation with penetratin.

    Science.gov (United States)

    Gil-Parrado, Shirley; Assfalg-Machleidt, Irmgard; Fiorino, Ferdinando; Deluca, Dominga; Pfeiler, Dietmar; Schaschke, Norbert; Moroder, Luis; Machleidt, Werner

    2003-03-01

    The ubiquitous calpains, mu- and m-calpain, have been implicated in essential physiological processes and various pathologies. Cell-permeable specific inhibitors are important tools to elucidate the roles of calpains in cultivated cells and animal models. The synthetic N-acetylated 27-mer peptide derived from exon B of the inhibitory domain 1 of human calpastatin (CP1B) is unique as a potent and highly selective reversible calpain inhibitor, but is poorly cell-permeant. By addition of N-terminal cysteine residues we have generated a disulfide-conjugated CP1B with the cell-penetrating 16-mer peptide penetratin derived from the third helix of the Antennapedia homeodomain protein. The inhibitory potency and selectivity of CP1B for calpain versus cathepsin B and L, caspase 3 and the proteasome was not affected by the conjugation with penetratin. The conjugate was shown to efficiently penetrate into living LCLC 103H cells, since it prevents ionomycin-induced calpain activation at 200-fold lower concentration than the non-conjugated inhibitor and is able to reduce calpain-triggered apoptosis of these cells. Penetratin-conjugated CP1B seems to be a promising alternative to the widely used cell-permeable peptide aldehydes (e.g. calpain inhibitor 1) which inhibit the lysosomal cathepsins and partially the proteasome as well or even better than the calpains. PMID:12715890

  9. Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors

    OpenAIRE

    Marton Siklos; Manel BenAissa; Thatcher, Gregory R.J.

    2015-01-01

    Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families...

  10. In silico affinity profiling of neuroactive polyphenols for post-traumatic calpain inactivation: a molecular docking and atomistic simulation sensitivity analysis.

    Science.gov (United States)

    Kumar, Pradeep; Choonara, Yahya E; Pillay, Viness

    2015-01-01

    Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain's proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM), molecular dynamics (MD), and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin) and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM) demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain-calpain inhibitor molecular complexes' energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies. PMID:25546626

  11. The calpain inhibitor MDL28170 induces the expression of apoptotic markers in Leishmania amazonensis promastigotes.

    Directory of Open Access Journals (Sweden)

    Fernanda A Marinho

    Full Text Available BACKGROUND: Human cutaneous leishmaniasis is caused by distinct species, including Leishmania amazonensis. Treatment of cutaneous leishmaniasis is far from satisfactory due to increases in drug resistance and relapses, and toxicity of compounds to the host. As a consequence for this situation, the development of new leishmanicidal drugs and the search of new targets in the parasite biology are important goals. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the mechanism of death pathway induced by the calpain inhibitor MDL28170 on Leishmania amazonensis promastigote forms. The combined use of different techniques was applied to contemplate this goal. MDL28170 treatment with IC50 (15 µM and two times the IC50 doses induced loss of parasite viability, as verified by resazurin assay, as well as depolarization of the mitochondrial membrane, which was quantified by JC-1 staining. Scanning and transmission electron microscopic images revealed drastic alterations on the parasite morphology, some of them resembling apoptotic-like death, including cell shrinking, surface membrane blebs and altered chromatin condensation pattern. The lipid rearrangement of the plasma membrane was detected by Annexin-V labeling. The inhibitor also induced a significant increase in the proportion of cells in the sub-G0/G1 phase, as quantified by propidium iodide staining, as well as genomic DNA fragmentation, detected by TUNEL assay. In cells treated with MDL28170 at two times the IC50 dose, it was also possible to observe an oligonucleossomal DNA fragmentation by agarose gel electrophoresis. CONCLUSIONS/SIGNIFICANCE: The data presented in the current study suggest that MDL28170 induces apoptotic marker expression in promastigotes of L. amazonensis. Altogether, the results described in the present work not only provide a rationale for further exploration of the mechanism of action of calpain inhibitors against trypanosomatids, but may also widen the

  12. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    OpenAIRE

    MartinKChilders; DanielJBogan; MelanieHolder; HanselGreiner; RobertGrange

    2012-01-01

    Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD). Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystroph...

  13. Preliminary study on the effect of caspase-6 and calpain inhibitors on postmortem proteolysis of myofibrillar proteins in chicken breast muscle.

    Science.gov (United States)

    Huang, Ming; Huang, Feng; Ma, Hanjun; Xu, Xinglian; Zhou, Guanghong

    2012-03-01

    The objective was to determine the effect of three different protease inhibitors, caspase-6 specific inhibitor VEID-CHO (N-Acetyl-Val-Glu-Ile-Asp-al), calpain inhibitor leupeptin or calpain inhibitor EGTA on protein degradation, ultrastructure of myofibrils and calpain activity during postmortem (PM) aging of chicken muscle. Results showed that proteolysis of nebulin, troponin-T and desmin during 14-days postmortem storage were inhibited significantly by leupeptin. Inhibitive effects of VEID-CHO and EGTA on these protein degradations were significant only during 1-day postmortem storage. The activities of calpains were inhibited noticeably by leupeptin and EGTA, but not by VEID-CHO. Samples treated with VEID-CHO, leupeptin and EGTA retarded structural disruption of chicken muscle fibers. These results demonstrate that calpain is a major contributor to PM tenderization; while caspase-6 plays, if any, a minimal role in the conversion of chicken muscle to meat. PMID:22098823

  14. Overexpression of the calpain-specific inhibitor calpastatin reduces human alpha-Synuclein processing, aggregation and synaptic impairment in [A30P]αSyn transgenic mice.

    Science.gov (United States)

    Diepenbroek, Meike; Casadei, Nicolas; Esmer, Hakan; Saido, Takaomi C; Takano, Jiro; Kahle, Philipp J; Nixon, Ralph A; Rao, Mala V; Melki, Ronald; Pieri, Laura; Helling, Stefan; Marcus, Katrin; Krueger, Rejko; Masliah, Eliezer; Riess, Olaf; Nuber, Silke

    2014-08-01

    Lewy bodies, a pathological hallmark of Parkinson's disease (PD), contain aggregated alpha-synuclein (αSyn), which is found in several modified forms and can be discovered phosphorylated, ubiquitinated and truncated. Aggregation-prone truncated species of αSyn caused by aberrant cleavage of this fibrillogenic protein are hypothesized to participate in its sequestration into inclusions subsequently leading to synaptic dysfunction and neuronal death. Here, we investigated the role of calpain cleavage of αSyn in vivo by generating two opposing mouse models. We crossed into human [A30P]αSyn transgenic (i) mice deficient for calpastatin, a calpain-specific inhibitor, thus enhancing calpain activity (SynCAST(-)) and (ii) mice overexpressing human calpastatin leading to reduced calpain activity (SynCAST(+)). As anticipated, a reduced calpain activity led to a decreased number of αSyn-positive aggregates, whereas loss of calpastatin led to increased truncation of αSyn in SynCAST(-). Furthermore, overexpression of calpastatin decreased astrogliosis and the calpain-dependent degradation of synaptic proteins, potentially ameliorating the observed neuropathology in [A30P]αSyn and SynCAST(+) mice. Overall, our data further support a crucial role of calpains, particularly of calpain 1, in the pathogenesis of PD and in disease-associated aggregation of αSyn, indicating a therapeutic potential of calpain inhibition in PD. PMID:24619358

  15. In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar

    2014-12-01

    Full Text Available Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain’s proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM, molecular dynamics (MD, and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain–calpain inhibitor molecular complexes’ energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies.

  16. Calpain Inhibitor Reduces Cancer-induced Bone Pain Possibly Through Inhibition of Osteoclastogenesis in Rat Cancer-induced Bone Pain Model

    Institute of Scientific and Technical Information of China (English)

    Jia-Ying Xu; Yu Jiang; Wei Liu; Yu-Guang Huang

    2015-01-01

    Background:Calpain,a calcium-dependent cysteine protease,has been demonstrated to regulate osteoclastogenesis,which is considered one of the major reasons for cancer-induced bone pain (CIBP).In the present study,calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity.Methods:A rat CIBP model was established with intratibial injection of Walker 256 cells.Then,the efficacy of intraperitoneal administered calpain inhibitor Ⅲ (MDL28170,1 mg/kg) on mechanical withdrawal threshold (MWT) of bilateral hind paws was examined on postoperative days (PODs) 2,5,8,11,and 14.On POD 14,the calpain inhibitor's effect on tumor bone tartrate-resistant acid phosphatase (TRAP) stain and radiology was also carefully investigated.Results:Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5,8,and 11 (P < 0.05).TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05).However,bone resorption and destruction measured by radiographs showed no difference between the two groups.Conclusions:Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model.It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis.Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

  17. Calpain Inhibitor Reduces Cancer-induced Bone Pain Possibly Through Inhibition of Osteoclastogenesis in Rat Cancer-induced Bone Pain Model

    Directory of Open Access Journals (Sweden)

    Jia-Ying Xu

    2015-01-01

    Full Text Available Background: Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain (CIBP. In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity. Methods: A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III (MDL28170, 1 mg/kg on mechanical withdrawal threshold (MWT of bilateral hind paws was examined on postoperative days (PODs 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor′s effect on tumor bone tartrate-resistant acid phosphatase (TRAP stain and radiology was also carefully investigated. Results: Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 (P < 0.05. TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05. However, bone resorption and destruction measured by radiographs showed no difference between the two groups. Conclusions: Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

  18. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (O08529) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (80 kDa M-calpain subunit) (CALP80) CAN2_MOUSE 5e-53 ...

  19. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (O08529) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (80 kDa M-calpain subunit) (CALP80) CAN2_MOUSE 1e-38 ...

  20. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (P17655) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (Calpain large polypeptide L2) CAN2_HUMAN 6e-40 ...

  1. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (P17655) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (Calpain large polypeptide L2) CAN2_HUMAN 2e-53 ...

  2. UniProt search blastx result: AK287903 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287903 J065211G19 P17655|CAN2_HUMAN Calpain-2 catalytic subunit precursor (EC 3.4.22.53) (Calpain...-2 large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain...) (Calpain large polypeptide L2) - Homo sapiens (Human) 0 ...

  3. UniProt search blastx result: AK287903 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287903 J065211G19 O08529|CAN2_MOUSE Calpain-2 catalytic subunit precursor (EC 3.4.22.53) (Calpain...-2 large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain...) (80 kDa M-calpain subunit) (CALP80) - Mus musculus (Mouse) 0 ...

  4. Arabidopsis CDS blastp result: AK121261 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121261 J023104H13 At1g55350.4 calpain-type cysteine protease family identical to calpain...-like protein GI:20268660 from [Arabidopsis thaliana]; contains Pfam profiles: PF00648 Calpain family... cysteine protease, PF01067 Calpain large subunit,domain III; identical to cDNA calpain-like protein GI:20268659 0.0 ...

  5. Arabidopsis CDS blastp result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 At1g55350.4 calpain-type cysteine protease family identical to calpain...-like protein GI:20268660 from [Arabidopsis thaliana]; contains Pfam profiles: PF00648 Calpain family... cysteine protease, PF01067 Calpain large subunit,domain III; identical to cDNA calpain-like protein GI:20268659 1e-150 ...

  6. Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells transplantation.

    Science.gov (United States)

    Wang, Chao; Shi, Dongling; Song, Xinghui; Chen, Yingying; Wang, Linlin; Zhang, Xiaoming

    2016-07-01

    Bone marrow mesenchymal stem cells (BMSCs) therapy for tissue repair is limited by low survival of cells transplanted in the recipient sites after spinal cord injury (SCI). Here, we investigated the effects of a calpain inhibitor (MDL28170) on BMSCs survival by a rat model of spinal cord injury in vitro and in vivo. Conditioned medium from hypoxia injured VSC4.1 motor neurons (Hypoxia-CM) were collected to mimic the micro-environment of injured spinal cord. Tunicamycin was also applied to induce endoplasmic reticulum (ER) stress in BMSCs. The CCK-8 assay, LDH leakage assay and flow cytometer assay demonstrated that MDL28170 could enhance BMSCs survival in response to Hypoxia-CM and tunicamycin. Moreover, MDL28170 significantly enhanced GFP-positive BMSCs survival in vivo after transplantation into the contused spinal cord of SCI rats. The protective effects of MDL28170 on BMSCs survival may inhibit the activation of calpain and the downstream ER stress-induced apoptosis. The present results suggested for the first time that MDL28170 with BMSCs transplant helped to rescue cells in injured spinal cord by modulating the ER stress-induced apoptosis. The calpain inhibitor, MDL28170 may have the promising new strategies for promoting the survival of transplanted BMSCs on cell-based regenerative medicine. PMID:27137651

  7. The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low Side-Effect Profile.

    Science.gov (United States)

    Vengeliene, Valentina; Moeller, Achim; Meinhardt, Marcus W; Beardsley, Patrick M; Sommer, Wolfgang H; Spanagel, Rainer; Bespalov, Anton

    2016-03-01

    Preclinical studies revealed contribution of N-methyl-D-aspartate receptors (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but development of NMDAR antagonists for therapeutic use has been a challenge, in part due to severe side effects. One of the key intracellular events resulting from stimulation of NMDAR is activation of calpains-calcium-dependent cysteine proteases. Here we studied whether inhibition of calpains would produce therapeutic-like effects of NMDAR antagonists but without their NMDAR-mediated side-effect profile. The calpain inhibitor A-705253 (3-10 mg/kg) was tested in a model of cue-induced reinstatement of alcohol-seeking behavior in post-dependent Wistar rats and in an alcohol deprivation effect (ADE) model in long-term alcohol drinking Wistar rats, two behavioral models for alcohol-seeking and relapse, respectively. We also tested the effect of A-705253 on the saccharine deprivation effect (SDE) as a selectivity measure. Acute treatment with A-705253 dose-dependently reduced cue-induced reinstatement of alcohol-seeking behavior. Repeated administration of A-705253 caused significant reductions of relapse-like excessive alcohol intake during the post-abstinence drinking days, an effect that persisted during two more successive drug-free drinking weeks, which was selective for the ADE as the SDE was unaffected. However, A-705253 did not produce psychostimulant, cognition impairing (delayed-matching-to-position), or psychotomimetic effects (specifically, phencyclidine discriminative stimulus effects). Taken together, these results demonstrate the involvement of calpains in alcohol-seeking and relapse and present a rationale for a novel pharmacological intervention that may reduce craving and relapse with minimal side effects in alcohol-dependent patients. PMID:26216521

  8. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (Q92178) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_CHICK 3e-38 ...

  9. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (Q9GLG1) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_MACFA 3e-53 ...

  10. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (Q92178) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_CHICK 1e-51 ...

  11. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (Q07009) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_RAT 9e-52 ...

  12. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (Q9GLG1) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_MACFA 8e-40 ...

  13. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (P06814) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (Fragment) CAN2_RABIT 2e-16 ...

  14. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (Q92178) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_CHICK 3e-11 ...

  15. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (P06814) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (Fragment) CAN2_RABIT 6e-16 ...

  16. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (Q92178) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2... large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_CHICK 1e-11 ...

  17. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (Q07009) Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain-2 ...large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) CAN2_RAT 4e-38 ...

  18. UniProt search blastx result: AK287903 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287903 J065211G19 Q92178|CAN2_CHICK Calpain-2 catalytic subunit precursor (EC 3.4.22.53) (Calpain...-2 large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) - Gallus gallus (Chicken) 0 ...

  19. UniProt search blastx result: AK287903 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287903 J065211G19 P43367|CAN2_PIG Calpain-2 catalytic subunit (EC 3.4.22.53) (Calpain...-2 large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain) (Fragment) - Sus scrofa (Pig) 0 ...

  20. UniProt search blastx result: AK287903 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287903 J065211G19 Q9GLG1|CAN2_MACFA Calpain-2 catalytic subunit precursor (EC 3.4.22.53) (Calpain...-2 large subunit) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (M-calpain) (Millimolar-calpain

  1. Inhibitors of cysteine cathepsin and calpain do not prevent ultraviolet-B-induced apoptosis in human keratinocytes and HeLa cells

    DEFF Research Database (Denmark)

    Bang, Bo; Baadsgaard, Ole; Skov, Lone;

    2004-01-01

    Caspases, members of the cysteine protease family, execute UVB-induced apoptosis in several cell lines and keratinocytes. Several researchers investigating UVB-induced apoptosis have demonstrated a dose-dependent protective effect of the synthetic peptide caspase inhibitor zVAD-fmk. However, z......VAD-fmk displays a dose-dependent protective effect against UVB-induced apoptosis, even at doses higher than those required to block all known proapoptotic caspases. In addition, it is known that zVAD-fmk also inhibits other cysteine proteases including cathepsins and calpains, and these proteases have recently...... been demonstrated to play a role in the execution of programmed cell death induced by other stimuli, e.g. TNF-alpha. The purpose of the present study was therefore to investigate whether inhibitors of cysteine cathepsins and calpains could prevent UVB-induced apoptosis in HeLa cells and keratinocytes...

  2. Arabidopsis CDS blastp result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 At1g55350.4 calpain-type cysteine protease family identical to calpain...-like protein GI:20268660 from [Arabidopsis thaliana]; contains Pfam profiles: PF00648 Calpain famil...y cysteine protease, PF01067 Calpain large subunit,domain III; identical to cDNA calpain-like protein GI:20268659 0.0 ...

  3. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (P06815) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) (Fragment) CAN1_RABIT 6e-12 ...

  4. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (Q9GLG2) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MACFA 2e-12 ...

  5. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (P35750) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_PIG 2e-12 ...

  6. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (P97571) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_RAT 7e-41 ...

  7. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (Q27970) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_BOVIN 2e-39 ...

  8. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (Q9GLG2) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MACFA 2e-12 ...

  9. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (P07384) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_HUMAN 2e-12 ...

  10. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (P07384) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_HUMAN 1e-39 ...

  11. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (P35750) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_PIG 7e-52 ...

  12. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (O35350) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MOUSE 2e-53 ...

  13. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (P06815) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) (Fragment) CAN1_RABIT 8e-12 ...

  14. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (O35350) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MOUSE 9e-41 ...

  15. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (Q27970) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_BOVIN 2e-11 ...

  16. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (P97571) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_RAT 2e-11 ...

  17. SwissProt search result: AK065151 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065151 J013002B09 (P35750) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_PIG 4e-11 ...

  18. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (P35750) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_PIG 4e-39 ...

  19. SwissProt search result: AK065151 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065151 J013002B09 (P06815) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) (Fragment) CAN1_RABIT 2e-11 ...

  20. SwissProt search result: AK099458 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099458 J013022O12 (P06815) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) (Fragment) CAN1_RABIT 2e-11 ...

  1. SwissProt search result: AK072218 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072218 J013167O21 (Q9GLG2) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MACFA 1e-39 ...

  2. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (Q27970) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_BOVIN 2e-11 ...

  3. SwissProt search result: AK099458 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099458 J013022O12 (P35750) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_PIG 4e-11 ...

  4. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (P97571) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_RAT 2e-11 ...

  5. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (Q9GLG2) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MACFA 1e-52 ...

  6. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (O35350) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MOUSE 2e-11 ...

  7. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (P07384) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_HUMAN 2e-52 ...

  8. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (P07384) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_HUMAN 2e-12 ...

  9. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (Q27970) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_BOVIN 5e-52 ...

  10. SwissProt search result: AK064381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064381 002-108-E01 (P97571) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_RAT 1e-53 ...

  11. SwissProt search result: AK103409 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103409 J033128E16 (O35350) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1 ...large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_MOUSE 2e-11 ...

  12. SwissProt search result: AK059278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059278 001-025-C08 (P35750) Calpain-1 catalytic subunit (EC 3.4.22.52) (Calpain-1... large subunit) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (muCANP) (Micromolar-calpain) CAN1_PIG 2e-12 ...

  13. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Martin K Childers

    2012-01-01

    Full Text Available Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD. Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD. Young (6 week-old GRMD dogs were treated daily with either C101 (17mg/kg twice daily oral dose, n=9 or placebo (vehicle only, n=7 for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every two weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors. C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.

  14. Homology Modeling Study of Bovine μ-Calpain Inhibitor-Binding Domains

    Directory of Open Access Journals (Sweden)

    Han-Ha Chai

    2014-05-01

    Full Text Available The activated mammalian CAPN-structures, the CAPN/CAST complex in particular, have become an invaluable target model using the structure-based virtual screening of drug candidates from the discovery phase to development for over-activated CAPN linked to several diseases, such as post-ischemic injury and cataract formation. The effect of Ca2+-binding to the enzyme is thought to include activation, as well as the dissociation, aggregation, and autolysis of small regular subunits. Unfortunately, the Ca2+-activated enzyme tends to aggregate when provided as a divalent ion at the high-concentration required for the protease crystallization. This is also makes it very difficult to crystallize the whole-length enzyme itself, as well as the enzyme-inhibitor complex. Several parameters that influence CAPN activity have been investigated to determine its roles in Ca2+-modulation, autoproteolysis, phosphorylation, and intracellular distribution and inhibition by its endogenous inhibitor CAST. CAST binds and inhibits CAPN via its CAPN-inhibitor domains (four repeating domains 1–4; CAST1–4 when CAPN is activated by Ca2+-binding. An important key to understanding CAPN1 inhibition by CAST is to determine how CAST interacts at the molecular level with CAPN1 to inhibit its protease activity. In this study, a 3D structure model of a CAPN1 bound bovine CAST4 complex was built by comparative modeling based on the only known template structure of a rat CAPN2/CAST4 complex. The complex model suggests certain residues of bovine CAST4, notably, the TIPPKYQ motif sequence, and the structural elements of these residues, which are important for CAPN1 inhibition. In particular, as CAST4 docks near the flexible active site of CAPN1, conformational changes at the interaction site after binding could be directly related to CAST4 inhibitory activity. These functional interfaces can serve as a guide to the site-mutagenesis in research on bovine CAPN1 structure

  15. Identification of active Plasmodium falciparum calpain to establish screening system for Pf-calpain-based drug development

    Directory of Open Access Journals (Sweden)

    Soh Byoung

    2013-02-01

    Full Text Available Abstract Background With the increasing resistance of malaria parasites to available drugs, there is an urgent demand to develop new anti-malarial drugs. Calpain inhibitor, ALLN, is proposed to inhibit parasite proliferation by suppressing haemoglobin degradation. This provides Plasmodium calpain as a potential target for drug development. Pf-calpain, a cysteine protease of Plasmodium falciparum, belongs to calpain-7 family, which is an atypical calpain not harboring Ca2+-binding regulatory motifs. In this present study, in order to establish the screening system for Pf-calpain specific inhibitors, the active form of Pf-calpain was first identified. Methods Recombinant Pf-calpain including catalytic subdomain IIa (rPfcal-IIa was heterologously expressed and purified. Enzymatic activity was determined by both fluorogenic substrate assay and gelatin zymography. Molecular homology modeling was carried out to address the activation mode of Pf-calpain in the aspect of structural moiety. Results Based on the measurement of enzymatic activity and protease inhibitor assay, it was found that the active form of Pf-calpain only contains the catalytic subdomain IIa, suggesting that Pf-calpain may function as a monomeric form. The sequence prediction indicates that the catalytic subdomain IIa contains all amino acid residues necessary for catalytic triad (Cys-His-Asn formation. Molecular modeling suggests that the Pf-calpain subdomain IIa makes an active site, holding the catalytic triad residues in their appropriate orientation for catalysis. The mutation analysis further supports that those amino acid residues are functional and have enzymatic activity. Conclusion The identified active form of Pf-calpain could be utilized to establish high-throughput screening system for Pf-calpain inhibitors. Due to its unique monomeric structural property, Pf-calpain could be served as a novel anti-malarial drug target, which has a high specificity for malaria parasite

  16. Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

    Directory of Open Access Journals (Sweden)

    Daniela M Santos

    Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.

  17. Calpain I Inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    XUE Hong-jie; SHAN Hong-bo; LIU Jie; LI Wei-min; LI Yue; GONG Yong-tai; YANG Bao-feng; JIN Cheng-luo; SHENG Li; CHU Shan; ZHANG Li

    2008-01-01

    Background Atrial fibrillation (AF) is accompanied by atrial structural remodeling. Calpain activity is induced during AR To lest a causal relationship between calpain activation and atrial structural changes, N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, was utilized in a canine AF model.Methods Fifteen dogs were randomly divided into 3 groups: sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg-kg-1·d-1 in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain l localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography.Results Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis (rs=0.90 961, P<0.0001) was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM.Conclusions Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain Inhibition may therefore provide a possibility for therapeutic Intervention in AF.

  18. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  19. Neuroprotective effect of synthetic chalcone derivatives as competitive dual inhibitors against μ-calpain and cathepsin B through the downregulation of tau phosphorylation and insoluble Aβ peptide formation.

    Science.gov (United States)

    Jeon, Kyung-Hwa; Lee, Eunyoung; Jun, Kyu-Yeon; Eom, Ji-Eun; Kwak, Soo Yeon; Na, Younghwa; Kwon, Youngjoo

    2016-10-01

    A series of chalcone derivatives were synthesized and evaluated for their μ-calpain and cathepsin B inhibitory activities. Among the tested chalcone derivatives, two compounds, 7 and 11, showed potent inhibitory activities against μ-calpain and cathepsin B and were selected for further evaluation. Compounds 7 and 11 showed enzyme inhibitory activities at the cellular level and displayed neuroprotective effects against oxidative stress-induced apoptosis in SH-SY5Y cells, a human neuroblastoma cell line. Moreover, compounds 7 and 11 reduced p25 formation, tau phosphorylation and insoluble Aβ peptide formation. Enzyme kinetic experiments and docking studies revealed that compounds 7 and 11 competitively inhibited both μ-calpain and cathepsin B enzymes. PMID:27318120

  20. Inhibiting calpain, rescuing cells.

    OpenAIRE

    Robinson, A.

    1996-01-01

    Drs. John Elce and Peter Davies, biochemists at Queen's University, Kingston, Ont., are investigating the molecular structure of calpain, an enzyme that has been implicated in the cellular damage that occurs after such events as myocardial infarction and stroke. This damage is precipitated by an imbalance in the regulation of calpain that arises as an indirect result of ischemia. Elce and Davies hope that their research, which involves techniques such as recombinant DNA technology and x-ray c...

  1. Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells

    Science.gov (United States)

    Koh, T. J.; Tidball, J. G.

    2000-01-01

    We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide donor sodium nitroprusside prevented many of the effects of calcium ionophore on C(2)C(12) muscle cells, including preventing talin proteolysis and release into the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular protein. These results indicate that nitric oxide inhibition of calpain protected the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell-permeable calpastatin peptide also protected the cells from proteolysis, confirming that ionophore-induced proteolysis was primarily calpain mediated. The activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside, and this inhibition was reversed by dithiothreitol. Previous incubation with the active site-targeted calpain inhibitor I prevented most of the sodium nitroprusside-induced inhibition of m-calpain activity. These data suggest that nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site cysteine. The results of this study indicate that nitric oxide produced endogenously by skeletal muscle and other cell types has the potential to inhibit m-calpain activity and cytoskeletal proteolysis.

  2. The calpain/calpastatin system has opposing roles in growth and metastatic dissemination of melanoma.

    Directory of Open Access Journals (Sweden)

    Quentin Raimbourg

    Full Text Available Conventional calpains are ubiquitous cysteine proteases whose activity is promoted by calcium signaling and specifically limited by calpastatin. Calpain expression has been shown to be increased in human malignant cells, but the contribution of the calpain/calpastatin system in tumorigenesis remains unclear. It may play an important role in tumor cells themselves (cell growth, migration, and a contrario cell death and/or in tumor niche (tissue infiltration by immune cells, neo-angiogenesis. In this study, we have used a mouse model of melanoma as a tool to gain further understanding of the role of calpains in tumor progression. To determine the respective importance of each target, we overexpressed calpastatin in tumor and/or host in isolation. Our data demonstrate that calpain inhibition in both tumor and host blunts tumor growth, while paradoxically increasing metastatic dissemination to regional lymph nodes. Specifically, calpain inhibition in melanoma cells limits tumor growth in vitro and in vivo but increases dissemination by amplifying cell resistance to apoptosis and accelerating migration process. Meanwhile, calpain inhibition restricted to host cells blunts tumor infiltration by immune cells and angiogenesis required for antitumor immunity, allowing tumor cells to escape tumor niche and disseminate. The development of highly specific calpain inhibitors with potential medical applications in cancer should take into account the opposing roles of the calpain/calpastatin system in initial tumor growth and subsequent metastatic dissemination.

  3. Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation.

    Directory of Open Access Journals (Sweden)

    Jacek M Witkowski

    2008-01-01

    Full Text Available Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases--calpains--is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors--calpastatins. The calpain-calpastatin system within living cells is in a fragile balance, which depends on both partners. The interdependence of calpain--a protease--and calpastatin--an endogenous inhibitor and at the same time a substrate for this enzyme makes any assessment of actual activity of this enzyme in the cells very difficult. In this work we made an attempt to estimate and compare the activity of calpain in human peripheral blood lymphocytes by assessing the levels of limited proteolysis of calpastatin in these cells by western blot, while at the same time the levels of calpain protein inside these cells was measured by flow cytometry. Our results indicate that it is possible to compare (semi-quantitatively the activities of calpain in peripheral blood CD4+ and CD19+ lymphocytes from various donors that way. Preliminary results showed that calpain activity is increased in the CD4+ T cells isolated from peripheral blood of rheumatoid arthritis patients as compared to control lymphocytes. Extremely high intrinsic activity of calpain was detected in chronic lymphocytic leukemia (CD19+ cells. All this confirms the detection of immunoreactive products of calpastatin as a good maker of endogenous calpain activity.

  4. Calpeptin, not calpain, directly inhibits an ion channel of the inner mitochondrial membrane.

    Science.gov (United States)

    Derksen, Maria; Vorwerk, Christian; Siemen, Detlef

    2016-05-01

    The permeability transition pore (PTP) of inner mitochondrial membranes is a large conductance pathway for ions up to 1500 Da which opening is responsible for ion equilibration and loss of membrane potential in apoptosis and thus in several neurodegenerative diseases. The PTP can be regulated by the Ca(2+)-activated mitochondrial K channel (BK). Calpains are Ca(2+)-activated cystein proteases; calpeptin is an inhibitor of calpains. We wondered whether calpain or calpeptin can modulate activity of PTP or BK. Patch clamp experiments were performed on mitoplasts of rat liver (PTP) and of an astrocytoma cell line (BK). Channel-independent open probability (P o) was determined (PTP) and, taking into account the number of open levels, NPo by single channel analysis (BK). We find that PTP in the presence of Ca(2+) (200 μM) is uninfluenced by calpain (13 nM) and shows insignificant decrease by the calpain inhibitor calpeptin (1 μM). The NPo of the BK is insensitive to calpain (54 nM), too. However, it is significantly and reversibly inhibited by the calpain inhibitor calpeptin (IC50 = 42 μM). The results agree with calpeptin-induced activation of the PTP via inhibition of the BK. Screening experiments with respirometry show calpeptin effects, fitting to inhibition of the BK by calpeptin, and strong inhibition of state 3 respiration. PMID:26108743

  5. Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains

    Energy Technology Data Exchange (ETDEWEB)

    Moldoveanu, Tudor; Gehring, Kalle; Green, Douglas R. (McGill); (SJCH)

    2009-01-15

    Ca{sup 2+}-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0 A structure of Ca{sup 2+}-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca{sup 2+}, illustrating key residues in a peripheral domain that serve to stabilize the protease core on Ca{sup 2+} binding. Fully activated calpain binds ten Ca{sup 2+} atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.

  6. Concerted Multi-Pronged Attack by Calpastatin to Occlude the Catalytic Cleft of Heterodimeric Calpains

    Energy Technology Data Exchange (ETDEWEB)

    Moldoveanu, T.; Gehring, K; Green, D

    2008-01-01

    The Ca{sup 2+}-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0{angstrom} structure of Ca{sup 2+}-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca{sup 2+}, illustrating key residues in a peripheral domain that serve to stabilize the protease core on Ca{sup 2+} binding. Fully activated calpain binds ten Ca{sup 2+} atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.

  7. Calpains and Coronary Vascular Disease.

    Science.gov (United States)

    Potz, Brittany A; Sabe, Ashraf A; Abid, M Ruhul; Sellke, Frank W

    2016-01-01

    Despite many advances in percutaneous and surgical interventions in the treatment of coronary artery disease (CAD), up to one-third of patients are still either not candidates or receive suboptimal revascularization. Calpains are a class of calcium-activated non-lysosomal cysteine proteases that serve as a proteolytic unit for cellular homeostasis. Uncontrolled activation of calpain has been found to be involved in the pathogenesis of myocardial reperfusion injury, cardiac hypertrophy, myocardial stunning and cardiac ischemia. Inhibition of calpains has been shown to significantly attenuate myocardial stunning and reduced infarct size after ischemia-reperfusion. Calpain inhibition therefore serves as a potential medical therapy for patients suffering from a number of diseases, including CAD. PMID:26489456

  8. Erythropoietin Modulates Cerebral and Serum Degradation Products from Excess Calpain Activation following Prenatal Hypoxia-Ischemia.

    Science.gov (United States)

    Jantzie, Lauren L; Winer, Jesse L; Corbett, Christopher J; Robinson, Shenandoah

    2016-01-01

    Preterm infants suffer central nervous system (CNS) injury from hypoxia-ischemia and inflammation - termed encephalopathy of prematurity. Mature CNS injury activates caspase and calpain proteases. Erythropoietin (EPO) limits apoptosis mediated by activated caspases, but its role in modulating calpain activation has not yet been investigated extensively following injury to the developing CNS. We hypothesized that excess calpain activation degrades developmentally regulated molecules essential for CNS circuit formation, myelination and axon integrity, including neuronal potassium-chloride co-transporter (KCC2), myelin basic protein (MBP) and phosphorylated neurofilament (pNF), respectively. Further, we predicted that post-injury EPO treatment could mitigate CNS calpain-mediated degradation. Using prenatal transient systemic hypoxia-ischemia (TSHI) in rats to mimic CNS injury from extreme preterm birth, and postnatal EPO treatment with a clinically relevant dosing regimen, we found sustained postnatal excess cortical calpain activation following prenatal TSHI, as shown by the cleavage of alpha II-spectrin (αII-spectrin) into 145-kDa αII-spectrin degradation products (αII-SDPs) and p35 into p25. Postnatal expression of the endogenous calpain inhibitor calpastatin was also reduced following prenatal TSHI. Calpain substrate expression following TSHI, including cortical KCC2, MBP and NF, was modulated by postnatal EPO treatment. Calpain activation was reflected in serum levels of αII-SDPs and KCC2 fragments, and notably, EPO treatment also modulated KCC2 fragment levels. Together, these data indicate that excess calpain activity contributes to the pathogenesis of encephalopathy of prematurity. Serum biomarkers of calpain activation may detect ongoing cerebral injury and responsiveness to EPO or similar neuroprotective strategies. PMID:26551007

  9. Cross-talk between calpain and caspase proteolytic systems during neuronal apoptosis.

    Science.gov (United States)

    Neumar, Robert W; Xu, Y Anne; Gada, Hemal; Guttmann, Rodney P; Siman, Robert

    2003-04-18

    Cross-talk between calpain and caspase proteolytic systems has complicated efforts to determine their distinct roles in apoptotic cell death. This study examined the effect of overexpressing calpastatin, the specific endogenous calpain inhibitor, on the activity of the two proteolytic systems following an apoptotic stimulus. Human SH-SY5Y neuroblastoma cells were stably transfected with full-length human calpastatin cDNA resulting in 20-fold overexpression based on Western blot and 5-fold greater calpain inhibitory activity in cell extracts. Wild type and calpastatin overexpressing (CST1) cells were neuronally differentiated and apoptosis-induced with staurosporine (0.1-1.0 microm). Calpastatin overexpression decreased calpain activation, increased caspase-3-like activity, and accelerated the appearance of apoptotic nuclear morphology. Following 0.1-0.2 microm staurosporine, plasma membrane integrity based on calcein-acetoxymethyl fluorescence was significantly greater at 24 h in differentiated CST1 compared with differentiated wild type cells. However, this protective effect was lost at higher staurosporine doses (0.5-1.0 microm), which resulted in pronounced caspase-mediated degradation of the overexpressed calpastatin. These results suggest a dual role for calpains during neuronal apoptosis. In the early execution phase, calpain down-regulates caspase-3-like activity and slows progression of apoptotic nuclear morphology. Subsequent calpain activity, facilitated by caspase-mediated degradation of calpastatin, contributes to plasma membrane disruption and secondary necrosis. PMID:12576481

  10. Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Sarah A Wernimont

    Full Text Available BACKGROUND: T cell activation and immune synapse formation require the appropriate activation and clustering of the integrin, LFA-1. Previous work has reported that the calpain family of calcium-dependent proteases are important regulators of integrin activation and modulate T cell adhesion and migration. However, these studies have been limited by the use of calpain inhibitors, which have known off-target effects. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used a LoxP/CRE system to specifically deplete calpain 4, a small regulatory calpain subunit required for expression and activity of ubiquitously expressed calpains 1 and 2, in CD4+ T cells. CD4+ and CD8+ T cells developed normally in Capn4(F/F:CD4-CRE mice and had severely diminished expression of Calpain 1 and 2, diminished talin proteolysis and impaired casein degradation. Calpain 4-deficient T cells showed no difference in adhesion or migration on the LFA-1 ligand ICAM-1 compared to control T cells. Moreover, there was no impairment in conjugation between Capn4(F/F:CD4-CRE T cells and antigen presenting cells, and the conjugates were still capable of polarizing LFA-1, PKC-theta and actin to the immune synapse. Furthermore, T cells from Capn4(F/F:CD4-CRE mice showed normal proliferation in response to either anti-CD3/CD28 coated beads or cognate antigen-loaded splenocytes. Finally, there were no differences in the rates of apoptosis following extrinsic and intrinsic apoptotic stimuli. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that calpain 4 is not necessary for LFA-1-mediated adhesion, conjugation or migration. These results challenge previous reports that implicate a central role for calpains in the regulation of T cell LFA-1 function.

  11. An eccentric calpain, CAPN3/p94/calpain-3.

    Science.gov (United States)

    Ono, Yasuko; Ojima, Koichi; Shinkai-Ouchi, Fumiko; Hata, Shoji; Sorimachi, Hiroyuki

    2016-03-01

    Calpains are Ca(2+)-regulated proteolytic enzymes that are involved in a variety of biological phenomena. Calpains process substrates by limited proteolysis to modulate various protein functions in the cell, and are thus called "modulator proteases." CAPN3, previously called p94 or calpain-3, has unique features that are not found in any of the other 14 human calpains, or even in other proteases. For instance, CAPN3 undergoes extremely rapid and exhaustive autodegradation. CAPN3 is also the first (and so far, the only) intracellular enzyme found to depend on Na(+) for its activation. CAPN3 has both proteolytic and non-proteolytic functions. It has the interesting distinction of being the only protease, other than a few virus proteases, with the ability to regain protease function after its autolytic dissociation; this occurs through a process known as intermolecular complementation (iMOC). Gene mutations causing CAPN3 defects are responsible for limb-girdle muscular dystrophy type 2A (LGMD2A). Unusual characteristics of CAPN3 have fascinated researchers, but have also hampered conventional biochemical analysis. In this review, we describe significant findings about CAPN3 from its discovery to the present, and suggest promising avenues for future CAPN3 research. PMID:26363099

  12. Contribution of postmortem muscle biochemistry to the delivery of consistent meat quality with particular focus on the calpain system.

    Science.gov (United States)

    Koohmaraie, M; Geesink, G H

    2006-09-01

    Tenderness has been repeatedly reported as the most important quality aspect of meat. However, a number of studies have shown that a significant portion of retail meat can be considered tough. As a consequence, a significant consumer segment is willing to pay a premium for guaranteed tender meat. However, apart from measuring the shear force, there is no reliable method to predict tenderness. Most of the branded meat programs therefore attempt to ensure eating quality by controlling some of the factors that affect tenderness. Meat tenderness is determined by the amount and solubility of connective tissue, sarcomere shortening during rigor development, and postmortem proteolysis of myofibrillar and myofibrillar-associated proteins. Given the effect of postmortem proteolysis on the muscle ultrastructure, titin and desmin are likely key substrates that determine meat tenderness. A large number of studies have shown that the calpain proteolytic system plays a central role in postmortem proteolysis and tenderization. In skeletal muscle, the calpain system consists of at least three proteases, μ-calpain, m-calpain and calpain 3, and an inhibitor of μ- and m-calpain, calpastatin. When activated by calcium, the calpains not only degrade subtrates, but also autolyze, leading to loss of activity. m-Calpain does not autolyze in postmortem muscle and is therefore not involved in postmortem tenderization. Results from a number of studies, including a study on calpain 3 knockout mice, have shown that calpain 3 is also not involved in postmortem proteolysis. However, a large number of studies, including a study on μ-calpain knockout mice, have shown that μ-calpain is largely, if not solely, responsible for postmortem tenderization. Research efforts in this area should, therefore, focus on elucidation of regulation of μ-calpain activity in postmortem muscle. Discovering the mechanisms of μ-calpain activity regulation and methods to promote μ-calpain activity should have a

  13. The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington’s Disease Mouse Models

    Directory of Open Access Journals (Sweden)

    Vanita Chopra

    2012-12-01

    Full Text Available Inhibition of sirtuin 2 (SIRT2 deacetylase mediates protective effects in cell and invertebrate models of Parkinson’s disease and Huntington’s disease (HD. Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans.

  14. Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells

    Science.gov (United States)

    Liu, Tongzheng; Schneider, Ryan A; Shah, Vaibhav; Huang, Yongcheng; Likhotvorik, Rostislav I; Keshvara, Lakhu; Hoyt, Dale G

    2009-01-01

    Background The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-γ (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC. Methods MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh) RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF), PD150606), cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain. Results LPS or IFN alone did not induce COX-2. However, treatment with 10 μg LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold) in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous μ-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1 reduced calpain activity

  15. Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells

    Directory of Open Access Journals (Sweden)

    Likhotvorik Rostislav I

    2009-06-01

    Full Text Available Abstract Background The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1, regulates turnover of inducible nitric oxide synthase (iNOS in murine aortic endothelial cells (MAEC stimulated with E. coli endotoxin (LPS and interferon-γ (IFN. Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX-2, in MAEC. Methods MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF, PD150606, cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain. Results LPS or IFN alone did not induce COX-2. However, treatment with 10 μg LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous μ-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1

  16. Chronic intermittent ethanol induced axon and myelin degeneration is attenuated by calpain inhibition.

    Science.gov (United States)

    Samantaray, Supriti; Knaryan, Varduhi H; Patel, Kaushal S; Mulholland, Patrick J; Becker, Howard C; Banik, Naren L

    2015-10-01

    Chronic alcohol consumption causes multifaceted damage to the central nervous system (CNS), underlying mechanisms of which are gradually being unraveled. In our previous studies, activation of calpain, a calcium-activated neutral protease has been found to cause detrimental alterations in spinal motor neurons following ethanol (EtOH) exposure in vitro. However, it is not known whether calpain plays a pivotal role in chronic EtOH exposure-induced structural damage to CNS in vivo. To test the possible involvement of calpain in EtOH-associated neurodegenerative mechanisms the present investigation was conducted in a well-established mouse model of alcohol dependence - chronic intermittent EtOH (CIE) exposure and withdrawal. Our studies indicated significant loss of axonal proteins (neurofilament light and heavy, 50-60%), myelin proteins (myelin basic protein, 20-40% proteolipid protein, 25%) and enzyme (2', 3'-cyclic-nucleotide 3'-phosphodiesterase, 21-55%) following CIE in multiple regions of brain including hippocampus, corpus callosum, cerebellum, and importantly in spinal cord. These CIE-induced deleterious effects escalated after withdrawal in each CNS region tested. Increased expression and activity of calpain along with enhanced ratio of active calpain to calpastatin (sole endogenous inhibitor) was observed after withdrawal compared to EtOH exposure. Pharmacological inhibition of calpain with calpeptin (25 μg/kg) prior to each EtOH vapor inhalation significantly attenuated damage to axons and myelin as demonstrated by immuno-profiles of axonal and myelin proteins, and Luxol Fast Blue staining. Calpain inhibition significantly protected the ultrastructural integrity of axons and myelin compared to control as confirmed by electron microscopy. Together, these findings confirm CIE exposure and withdrawal induced structural alterations in axons and myelin, predominantly after withdrawal and corroborate calpain inhibition as a potential protective strategy against

  17. Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells

    OpenAIRE

    Likhotvorik Rostislav I; Huang Yongcheng; Shah Vaibhav; Schneider Ryan A; Liu Tongzheng; Keshvara Lakhu; Hoyt Dale G

    2009-01-01

    Abstract Background The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-γ (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC. Methods MAEC, transduced with lenti...

  18. Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.

    Directory of Open Access Journals (Sweden)

    Anna Mikosik

    Full Text Available Childhood acute lymphoblastic leukemia (ALL blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1 gene transcription, protein amounts and activity (but not those of m-calpain, with calpastatin amount and transcription of its gene (CAST greatly varying were observed in CD19(+ ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk displayed increased amounts and activities of blast calpain. Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV significantly and in dose-dependent fashion increased the percentage of blasts entering apoptosis. Together, these findings make the CCS a potential new predictive tool and therapeutic target in childhood ALL.

  19. Accumulation of human full-length tau induces degradation of nicotinic acetylcholine receptor α4 via activating calpain-2

    Science.gov (United States)

    Yin, Yaling; Wang, Yali; Gao, Di; Ye, Jinwang; Wang, Xin; Fang, Lin; Wu, Dongqin; Pi, Guilin; Lu, Chengbiao; Zhou, Xin-Wen; Yang, Ying; Wang, Jian-Zhi

    2016-01-01

    Cholinergic impairments and tau accumulation are hallmark pathologies in sporadic Alzheimer’s disease (AD), however, the intrinsic link between tau accumulation and cholinergic deficits is missing. Here, we found that overexpression of human wild-type full-length tau (termed hTau) induced a significant reduction of α4 subunit of nicotinic acetylcholine receptors (nAChRs) with an increased cleavage of the receptor producing a ~55kDa fragment in primary hippocampal neurons and in the rat brains, meanwhile, the α4 nAChR currents decreased. Further studies demonstrated that calpains, including calpain-1 and calpain-2, were remarkably activated with no change of caspase-3, while simultaneous suppression of calpain-2 by selective calpain-2 inhibitor but not calpain-1 attenuated the hTau-induced degradation of α4 nAChR. Finally, we demonstrated that hTau accumulation increased the basal intracellular calcium level in primary hippocampal neurons. We conclude that the hTau accumulation inhibits nAChRs α4 by activating calpain-2. To our best knowledge, this is the first evidence showing that the intracellular accumulation of tau causes cholinergic impairments. PMID:27277673

  20. Calpain 3 is important for muscle regeneration

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Sveen, Marie-Louise; Duno, Morten;

    2012-01-01

    Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was...

  1. Calpastatin overexpression reduces oxidative stress-induced mitochondrial impairment and cell death in human neuroblastoma SH-SY5Y cells by decreasing calpain and calcineurin activation, induction of mitochondrial fission and destruction of mitochondrial fusion.

    Science.gov (United States)

    Tangmansakulchai, Kulvadee; Abubakar, Zuroida; Kitiyanant, Narisorn; Suwanjang, Wilasinee; Leepiyasakulchai, Chaniya; Govitrapong, Piyarat; Chetsawang, Banthit

    2016-09-01

    Calpain is an intracellular Ca(2+)-dependent protease, and the activation of calpain has been implicated in neurodegenerative diseases. Calpain activity can be regulated by calpastatin, an endogenous specific calpain inhibitor. Several lines of evidence have demonstrated a potential role of calpastatin in preventing calpain-mediated pathogenesis. Additionally, several studies have revealed that calpain activation and mitochondrial damage are involved in the cell death process; however, recent evidence has not clearly indicated a neuroprotective mechanism of calpastatin against calpain-dependent mitochondrial impairment in the process of neuronal cell death. Therefore, the purpose of this study was to investigate the potential ability of calpastatin to inhibit calpain activation and mitochondrial impairment in oxidative stress-induced neuron degeneration. Calpastatin was stably overexpressed in human neuroblastoma SH-SY5Y cells. In non-calpastatin overexpressing SH-SY5Y cells, hydrogen peroxide significantly decreased cell viability, superoxide dismutase activity, mitochondrial membrane potential, ATP production and mitochondrial fusion protein (Opa1) levels in the mitochondrial fraction but increased reactive oxygen species formation, calpain and calcineurin activation, mitochondrial fission protein (Fis1 and Drp1) levels in the mitochondrial fraction and apoptotic cells. Nevertheless, these toxic effects were abolished in hydrogen peroxide-treated calpastatin-overexpressing SH-SY5Y cells. The results of the present study demonstrate the potential ability of calpastatin to diminish calpain and calcineurin activation and mitochondrial impairment in neurons that are affected by oxidative damage. PMID:27453331

  2. Opposing roles for caspase and calpain death proteases in L-glutamate-induced oxidative neurotoxicity

    International Nuclear Information System (INIS)

    Oxidative glutamate toxicity in HT22 murine hippocampal cells is a model for neuronal death by oxidative stress. We have investigated the role of proteases in HT22 cell oxidative glutamate toxicity. L-glutamate-induced toxicity was characterized by cell and nuclear shrinkage and chromatin condensation, yet occurred in the absence of either DNA fragmentation or mitochondrial cytochrome c release. Pretreatment with the selective caspase inhibitors either benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (pan-caspase), N-acetyl-Leu-Glu-His-Asp-aldehyde (caspase 9) or N-acetyl-Ile-Glu-Thr-Asp-aldehyde (caspase 8), significantly increased L-glutamate-induced cell death with a corresponding increase in observed nuclear shrinkage and chromatin condensation. This enhancement of glutamate toxicity correlated with an increase in L-glutamate-dependent production of reactive oxygen species (ROS) as a result of caspase inhibition. Pretreating the cells with N-acetyl-L-cysteine prevented ROS production, cell shrinkage and cell death from L-glutamate as well as that associated with the presence of the pan-caspase inhibitor. In contrast, the caspase-3/-7 inhibitor N-acetyl-Asp-Glu-Val-Asp aldehyde was without significant effect. However, pretreating the cells with the calpain inhibitor N-acetyl-Leu-Leu-Nle-CHO, but not the cathepsin B inhibitor CA-074, prevented cell death. The cytotoxic role of calpains was confirmed further by: 1) cytotoxic dependency on intracellular Ca2+ increase, 2) increased cleavage of the calpain substrate Suc-Leu-Leu-Val-Tyr-AMC and 3) immunoblot detection of the calpain-selective 145 kDa α-fodrin cleavage fragment. We conclude that oxidative L-glutamate toxicity in HT22 cells is mediated via calpain activation, whereas inhibition of caspases-8 and -9 may exacerbate L-glutamate-induced oxidative neuronal damage through increased oxidative stress

  3. Postmortem calpain changes in ostrich skeletal muscle.

    Science.gov (United States)

    Chang, Ya-Shiou; Hsu, Dun-Hui; Stromer, Mavin H; Chou, Rong-Ghi R

    2016-07-01

    The objective of this study was to study the postmortem calpain change in ostrich muscle. Iliotibialis cranialis and Obturatorius medialis muscles were removed from the both sides of carcasses (n=8). The muscles from the left side were sampled after 0, 1, 2, 3, and 7days of storage at 5°C, while the right-side muscles were taken at 1-, 3-, and 7-day postmortem for shear force measurements. The results showed that the calpain-1 activity was not detected in ostrich muscle during the entire 7-day postmortem storage period, while the calpain-11 was. The unautolyzed calpain-11 activity decreased and the autolyzed calpain-11 activity increased with time postmortem. Desmin content and shear force did not change during postmortem storage although a minor degradation of desmin was observed. Therefore, our results suggest that limited postmortem proteolysis (as suggested by the limited degradation of desmin) and tenderization might be due to the lack of calpain-1 and/or insufficient calpain-11 activity present in ostrich muscle. PMID:26971307

  4. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

    International Nuclear Information System (INIS)

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI

  5. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yan; Li, Zheng; He, Yan; Shang, Dandan; Pan, Jigang; Wang, Hongmei; Chen, Huamei; Zhu, Zhuxia [Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China); Wan, Lei [Department of Pharmacology, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China); Wang, Xudong, E-mail: xdwang@gmc.edu.cn [Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China)

    2014-03-01

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI.

  6. Calpain-mediated cleavage of DARPP-32 in Alzheimer's disease.

    Science.gov (United States)

    Cho, Kwangmin; Cho, Mi-Hyang; Seo, Jung-Han; Peak, Jongjin; Kong, Kyoung-Hye; Yoon, Seung-Yong; Kim, Dong-Hou

    2015-10-01

    Toxicity induced by aberrant protein aggregates in Alzheimer's disease (AD) causes synaptic disconnection and concomitant progressive neurodegeneration that eventually impair cognitive function. cAMP-response element-binding protein (CREB) is a transcription factor involved in the molecular switch that converts short-term to long-term memory. Although disturbances in CREB function have been suggested to cause memory deficits in both AD and AD animal models, the mechanism of CREB dysfunction is still unclear. Here, we show that the dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32), a key inhibitor of protein phosphate-1 (PP-1) that regulates CREB phosphorylation, is cleaved by activated calpain in both AD brains and neuronal cells treated with amyloid-β or okadaic acid, a protein phosphatase-2A inhibitor that induces tau hyperphosphorylation and neuronal death. We found that DARPP-32 is mainly cleaved at Thr(153) by calpain and that this cleavage of DARPP-32 reduces CREB phosphorylation via loss of its inhibitory function on PP1. Our results suggest a novel mechanism of DARPP-32-CREB signalling dysregulation in AD. PMID:26178297

  7. Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

    International Nuclear Information System (INIS)

    We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca2+) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

  8. The intriguing Ca2+ requirement of calpain activation

    International Nuclear Information System (INIS)

    Mammalian ubiquitous μ- and m-calpains, as well as their Drosophila homologs, Calpain A and Calpain B, are Ca2+-activated cytoplasmic proteases that act by limited proteolysis of target proteins. Calpains are thought to be part of many cellular signaling pathways. These enzymes, however, require such high Ca2+ concentration for half-maximal activation in vitro, [Ca2+]0.5, that hardly ever occurs in intact cells. This major dilemma has pervaded the literature on calpains for decades. In this paper several considerations are put forward that challenge the orthodox view and envisage mechanisms that may govern calpain action in vivo. The 'unphysiologically' high Ca2+ demand for activation may turn out to be an evolutionarily adjusted safety device

  9. Calpain-10 and insulin resistance in human skeletal muscle

    OpenAIRE

    Norton, Luke

    2007-01-01

    Variation in the calpain-10 gene has been linked to a three-fold increased risk for type 2 diabetes in Pima Indian and some European populations. Furthermore, reduced skeletal muscle expression of calpain-10 is associated with reduced insulin mediated glucose disposal and carbohydrate oxidation. The skeletal muscle specific calpain-3 plays a key role in skeletal muscle integrity and has also been linked to insulin resistance in humans and rodents. The major aims of this thesis were to...

  10. Involvement of calpains in adult neurogenesis: implications for stroke

    OpenAIRE

    Vanessa Mendes Machado; Maria Inês Morte; Bruno Pereira Carreira; Maria Manuela Azevedo; Jiro eTakano; Nobuhisa eIwata; Saido, Takaomi C; Hannelore eAsmussen; Alan Rick Horwitz; Caetana Monteiro Carvalho; Inês Maria Araújo

    2015-01-01

    Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains. Inhibition of these proteases has been shown to reduce neuronal death in a variety of stroke mod...

  11. Massive expansion of the calpain gene family in unicellular eukaryotes

    Directory of Open Access Journals (Sweden)

    Zhao Sen

    2012-09-01

    Full Text Available Abstract Background Calpains are Ca2+-dependent cysteine proteases that participate in a range of crucial cellular processes. Dysfunction of these enzymes may cause, for instance, life-threatening diseases in humans, the loss of sex determination in nematodes and embryo lethality in plants. Although the calpain family is well characterized in animal and plant model organisms, there is a great lack of knowledge about these genes in unicellular eukaryote species (i.e. protists. Here, we study the distribution and evolution of calpain genes in a wide range of eukaryote genomes from major branches in the tree of life. Results Our investigations reveal 24 types of protein domains that are combined with the calpain-specific catalytic domain CysPc. In total we identify 41 different calpain domain architectures, 28 of these domain combinations have not been previously described. Based on our phylogenetic inferences, we propose that at least four calpain variants were established in the early evolution of eukaryotes, most likely before the radiation of all the major supergroups of eukaryotes. Many domains associated with eukaryotic calpain genes can be found among eubacteria or archaebacteria but never in combination with the CysPc domain. Conclusions The analyses presented here show that ancient modules present in prokaryotes, and a few de novo eukaryote domains, have been assembled into many novel domain combinations along the evolutionary history of eukaryotes. Some of the new calpain genes show a narrow distribution in a few branches in the tree of life, likely representing lineage-specific innovations. Hence, the functionally important classical calpain genes found among humans and vertebrates make up only a tiny fraction of the calpain family. In fact, a massive expansion of the calpain family occurred by domain shuffling among unicellular eukaryotes and contributed to a wealth of functionally different genes.

  12. The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis.

    Directory of Open Access Journals (Sweden)

    Sergey Kuznetsov

    Full Text Available BACKGROUND: NORE1A and RASSF1A are growth and tumour suppressors inactivated in a variety of cancers. Methylation of NORE1A and RASSF1A promoters is the predominant mechanism for downregulation of these proteins; however, other mechanisms are likely to exist. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a proteolysis of NORE1A and RASSF1A by calpains as alternative mechanism of their downregulation. Extracts of H358 cell line, a human bronchoalveolar carcinoma, and H460, a large cell carcinoma, were capable of proteolysis of NORE1A protein in the calpain-dependent manner. Likewise, RASSF1A tumor suppressor was proteolyzed by the H358 cell extract. Addition of calpain inhibitor to H358 and H460 cells growing in tissue culture resulted in re-expression of endogenous NORE1A. A survey of 10 human lung tumours revealed that three of them contain an activity capable of inducing NORE1A degradation. CONCLUSIONS/SIGNIFICANCE: Thus, degradation by calpains is a novel mechanism for downregulation of NORE1A and RASSF1A proteins and might be the mechanism allowing cancer cells to escape growth suppression.

  13. Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways

    International Nuclear Information System (INIS)

    Capsaicin, a pungent compound found in hot chili peppers, induces apoptotic cell death in various cell lines, however, the precise apoptosis signaling pathway is unknown. Here, we investigated capsaicin-induced apoptotic signaling in the human breast cell line MCF10A and found that it involves both endoplasmic reticulum (ER) stress and calpain activation. Capsaicin inhibited growth in a dose-dependent manner and induced apoptotic nuclear changes in MCF10A cells. Capsaicin also induced degradation of tumor suppressor p53; this effect was enhanced by the ER stressor tunicamycin. The proteasome inhibitor MG132 completely blocked capsaicin-induced p53 degradation and enhanced apoptotic cell death. Capsaicin treatment triggered ER stress by increasing levels of IRE1, GADD153/Chop, GRP78/Bip, and activated caspase-4. It led to an increase in cytosolic Ca2+, calpain activation, loss of the mitochondrial transmembrane potential, release of mitochondrial cytochrome c, and caspase-9 and -7 activation. Furthermore, capsaicin-induced the mitochondrial apoptotic pathway through calpain-mediated Bid translocation to the mitochondria and nuclear translocation of apoptosis-inducing factor (AIF). Capsaicin-induced caspase-9, Bid cleavage, and AIF translocation were blocked by calpeptin, and BAPTA and calpeptin attenuated calpain activation and Bid cleavage. Thus, both ER stress- and mitochondria-mediated death pathways are involved in capsaicin-induced apoptosis.

  14. Propofol Ameliorates Calpain-induced Collapsin Response Mediator Protein-2 Proteolysis in Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Yun Yu

    2015-01-01

    Full Text Available Background: Collapsin response mediator protein-2 (CRMP2, a multifunctional cytosolic protein highly expressed in the brain, is degraded by calpain following traumatic brain injury (TBI, possibly inhibiting posttraumatic neurite regeneration. Lipid peroxidation (LP is involved in triggering postinjury CRMP2 proteolysis. We examined the hypothesis that propofol could attenuate LP, calpain-induced CRMP2 degradation, and brain injury after TBI. Methods: A unilateral moderate controlled cortical impact injury was induced in adult male Sprague-Dawley rats. The animals were randomly divided into seven groups: Sham control group, TBI group, TBI + propofol groups (including propofol 1 h, 2 h, and 4 h groups, TBI + U83836E group and TBI + fat emulsion group. The LP inhibitor U83836E was used as a control to identify that antioxidation partially accounts for the potential neuroprotective effects of propofol. The solvent of propofol, fat emulsion, was used as the vehicle control. Ipsilateral cortex tissues were harvested at 24 h post-TBI. Immunofluorescent staining, Western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were used to evaluate LP, calpain activity, CRMP2 proteolysis and programmed cell death. The data were statistically analyzed using one-way analysis of variance and a paired t-test. Results: Propofol and U83836E significantly ameliorated the CRMP2 proteolysis. In addition, both propofol and U83836E significantly decreased the ratio of 145-kDa αII-spectrin breakdown products to intact 270-kDa spectrin, the 4-hydroxynonenal expression and programmed cell death in the pericontusional cortex at 24 h after TBI. There was no difference between the TBI group and the fat emulsion group. Conclusions: These results demonstrate that propofol postconditioning alleviates calpain-mediated CRMP2 proteolysis and provides neuroprotective effects following moderate TBI potentially by counteracting LP and reducing

  15. In vitro degradation of bovine myofibrils is caused by μ-calpain, not caspase-3.

    Science.gov (United States)

    Mohrhauser, D A; Underwood, K R; Weaver, A D

    2011-03-01

    Tenderness is a key palatability trait influencing perception of consumers of meat quality and is influenced by a multitude of factors, including postmortem proteolysis. A fundamental understanding of this biological mechanism regulating tenderness is necessary to decrease variability and increase consumer satisfaction. However, reports regarding the enzyme systems involved in postmortem tenderization are conflicting. Therefore, the objective of this study was to determine if caspase-3 is responsible for the degradation of myofibrillar proteins during aging. Bovine semitendinosus muscles were removed from 2 carcasses. Muscle from the left side of each carcass was excised 20 min postmortem and utilized for in vitro analysis of protein degradation. Muscle strips were dissected from the semitendinosus, restrained to maintain length, and placed in a neutral buffer containing protease inhibitors. Upon rigor completion, myofibrils were isolated from each strip and sarcomere length was determined. Samples with similar sarcomere lengths were selected to minimize the effect of sarcomere length on proteolysis. Myofibrils were then incubated at 22°C with μ-calpain, caspase-3, or μ-calpain + caspase-3 for 0.25, 1, 3, 24, 48, or 72 h at optimum pH for enzyme activity. The semitendinosus from the right side of each carcass was excised 1 d postmortem, cut into 2.54-cm steaks, vacuum-packaged, and allowed to age for 2, 4, 7, or 10 d to evaluate normal protein degradation during beef aging. Proteolysis of troponin T, α-actinin, and desmin was monitored using SDS-PAGE and Western blotting techniques, whereas proteolysis of titin and nebulin was monitored using SDS-vertical agarose gel electrophoresis and Western blotting. Analysis of Western blots revealed no change in abundance of intact troponin T, desmin, titin, or nebulin over time in myofibrils incubated with caspase-3. However, abundance of these proteins subjected to digestion with μ-calpain and μ-calpain + caspase-3

  16. SwissProt search result: AK070925 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070925 J023070O07 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prote ... in) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 6e-11 ...

  17. SwissProt search result: AK073781 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073781 J033068H10 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prote ... in) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 1e-15 ...

  18. SwissProt search result: AK102207 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102207 J033087H03 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prote ... in) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 1e-15 ...

  19. SwissProt search result: AK070043 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070043 J023039E14 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prote ... in) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 3e-11 ...

  20. SwissProt search result: AK242300 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242300 J075192P11 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prote ... in) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 9e-15 ...

  1. SwissProt search result: AK069449 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069449 J023020E21 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prote ... in) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 2e-15 ...

  2. UniProt search blastx result: AK287588 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287588 J065045K19 P01010|A1AT_PAPAN Alpha-1-antitrypsin precursor (Alpha-1 protease inhibitor) ... 1-antiproteinase) (AAT) (Fragment) - Papio anubis (Olive ... baboon) 1.00E-17 ...

  3. Inhibitors

    Science.gov (United States)

    ... wrong place in the body. Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from ... body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor ...

  4. AB230. Calpain inhibition improves diabetic erectile dysfunction in rats

    Science.gov (United States)

    Li, Hao; Wang, Tao; Liu, Jihong

    2016-01-01

    Objective Diabetic erectile dysfunction is an intractable disease which results from both vascular and nervous dysfunction in penis. Calpain mediates the vascular dysfunction during hyperglycemia and is involved in some neurodegenerative diseases. This study was designed to investigate the role of calpain inhibition in improving diabetic erectile dysfunction in rats. Methods Type 1 diabetes was induced by intraperitoneal injection of streptozotocin at the dose of 60 mg/kg in rats. After 2 months, diabetic erectile dysfunction was confirmed by apomorphine test. Then the animals were divided into three groups: (I) nondiabetic control groups, (II) diabetic rats + vehicle and (III) diabetic rats + MDL28170. Two weeks later the erectile function was measured by electrical stimulation of the cavernous nerve and the ratio between intracavernosal pressure (ICP) and mean systemic arterial blood pressure (MAP) at the peak of erectile response was calculated. After that penis tissue was harvested. Calpain activity in corpus cavernosum was measured by western blot. Neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) were observed by immunohistochemistry and western blot. The endothelial content in the cavernosum was measured by immunohistochemistry. Results The calpain activity was increased in diabetic rats and inhibited by MDL28170. The erectile function was improved by MDL28170 treatment. The expression of nNOS and eNOS, as well as the content of endothelium in corpus cavernosum were also increased by inhibition of calpain. Conclusions Calpain activation may play a role in the erectile dysfunction of diabetic rats. Inhibition of calpain could improve diabetic erectile dysfunction by increasing expression of nNOS and eNOS in the corpus cavernosum. This could be a novel therapeutic target to protect the erectile function in diabetic patient.

  5. Analysis of calpain-3 protein in muscle biopsies of different muscular dystrophies from India

    OpenAIRE

    Renjini, R.; Gayathri, N.; A Nalini; Bharath, M.M. Srinivas

    2012-01-01

    Background & objectives: Calpain-3, a Ca2+-dependent protease has been implicated in the pathology of neuromuscular disorders (NMDs). The current study aimed to analyze calpain-3 expression in cases diagnosed as muscular dystrophy from the Indian population. Methods: Calpain-3 Western blot analysis in muscle biopsies of immunohistochemically confirmed cases of Duchenne muscular dystrophy (DMD) (n=10), dysferlinopathy (n=30) and sarcoglycanopathy (n=8) was carried out. Calpain-3 Western blotti...

  6. Calpain 3 is a rapid-action, unidirectional proteolytic switch central to muscle remodeling.

    Directory of Open Access Journals (Sweden)

    Antoine de Morrée

    Full Text Available Calpain 3 (CAPN3 is a cysteine protease that when mutated causes Limb Girdle Muscular Dystrophy 2A. It is thereby the only described Calpain family member that genetically causes a disease. Due to its inherent instability little is known of its substrates or its mechanism of activity and pathogenicity. In this investigation we define a primary sequence motif underlying CAPN3 substrate cleavage. This motif can transform non-related proteins into substrates, and identifies >300 new putative CAPN3 targets. Bioinformatic analyses of these targets demonstrate a critical role in muscle cytoskeletal remodeling and identify novel CAPN3 functions. Among the new CAPN3 substrates are three E3 SUMO ligases of the Protein Inhibitor of Activated Stats (PIAS family. CAPN3 can cleave PIAS proteins and negatively regulates PIAS3 sumoylase activity. Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation, with strong implications for muscle remodeling.

  7. The calpain-suppressing effects of olesoxime in Huntington's disease

    Science.gov (United States)

    Weber, Jonasz J.; Ortiz Rios, Midea M.; Riess, Olaf; Clemens, Laura E.; Nguyen, Huu P.

    2016-01-01

    ABSTRACT Olesoxime, a small molecule drug candidate, has recently attracted attention due to its significant beneficial effects in models of several neurodegenerative disorders including Huntington's disease. Olesoxime's neuroprotective effects have been assumed to be conveyed through a direct, positive influence on mitochondrial function. In a long-term treatment study in BACHD rats, the latest rat model of Huntington's disease, olesoxime revealed a positive influence on mitochondrial function and improved specific behavioral and neuropathological phenotypes. Moreover, a novel target of the compound was discovered, as olesoxime was found to suppress the activation of the calpain proteolytic system, a major contributor to the cleavage of the disease-causing mutant huntingtin protein into toxic fragments, and key player in degenerative processes in general. Results from a second model of Huntington's disease, the HdhQ111 knock-in mouse, confirm olesoxime's calpain-suppressing effects and support the therapeutic value of olesoxime for Huntington's disease and other disorders involving calpain overactivation.

  8. Calpain Activity Is Generally Elevated during Transformation but Has Oncogene-Specific Biological Functions

    Directory of Open Access Journals (Sweden)

    N.O. Carragher

    2004-01-01

    Full Text Available Several oncogene and tumor-suppressor gene products are known substrates for the calpain family of cysteine proteases, and calpain is required for transformation by v-src and tumor invasion. Thus, we have now addressed whether calpain is generally associated with transformation and how calpain contributes to oncogene function. Our results demonstrate that calpain activity is enhanced upon transformation induced by the v-Src, v-Jun, v-Myc, k-Ras, and v-Fos oncoproteins. Furthermore, elevated calpain activity commonly promotes focal adhesion remodelling, disruption of actin cytoskeleton, morphological transformation, and cell migration, although proteolysis of target substrates (such as focal adhesion kinase, talin, and spectrin is differently specified by individual oncoproteins. Interestingly, v-Fos differs from other common oncoproteins in not requiring calpain activity for actin/adhesion remodelling or migration of v-Fos transformed cells. However, anchorage-independent growth of all transformed cells is sensitive to calpain inhibition. In addition, elevated calpain activity contributes to oncogene-induced apoptosis associated with transformation by v-Myc. Taken together, these studies demonstrate that calpain activity is necessary for full cellular transformation induced by common oncoproteins, but has distinct roles in oncogenic events induced by individual transforming proteins. Thus, targeting calpain activity may represent a useful general strategy for interfering with activated protooncogenes in cancer cells.

  9. GenBank blastx search result: AK287588 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287588 J065045K19 BT025406.1 BT025406 Bos taurus serpin peptidase inhibitor, clad...e E (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1), mRNA, complete cds. MAM 9e-21 0 ...

  10. Cleavage of desmin by cysteine proteases: Calpains and cathepsin B

    DEFF Research Database (Denmark)

    Baron, Caroline; Jacobsen, S.; Purslow, P.P.

    2004-01-01

    sequential C-terminal degradation pattern characteristic of this dipeptylpeptidase. The substrate primary structure was not found to be essential for regulation of the proteolytic activity of the cysteine peptidases studied. However, the degradation patterns obtained imply that calpains are involved in...

  11. Propofol Ameliorates Calpain-induced Collapsin Response Mediator Protein-2 Proteolysis in Traumatic Brain Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Yun Yu; Min-Yu Jian; Yun-Zhen Wang; Ru-Quan Han

    2015-01-01

    Background:Collapsin response mediator protein-2 (CRMP2),a multifunctional cytosolic protein highly expressed in the brain,is degraded by calpain following traumatic brain injury (TBI),possibly inhibiting posttraumatic neurite regeneration.Lipid peroxidation (LP) is involved in triggering postinjury CRMP2 proteolysis.We examined the hypothesis that propofol could attenuate LP,calpain-induced CRMP2 degradation,and brain injury after TBI.Methods:A unilateral moderate controlled cortical impact injury was induced in adult male Sprague-Dawley rats.The animals were randomly divided into seven groups:Sham control group,TBI group,TBI + propofol groups (including propofol 1 h,2 h,and 4 h groups),TBI + U83836E group and TBI + fat emulsion group.The LP inhibitor U83836E was used as a control to identify that antioxidation partially accounts for the potential neuroprotective effects of propofol.The solvent of propofol,fat emulsion,was used as the vehicle control.Ipsilateral cortex tissues were harvested at 24 h post-TBI.Immunofluorescent staining,Western blot analysis,and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were used to evaluate LP,calpain activity,CRMP2 proteolysis and programmed cell death.The data were statistically analyzed using one-way analysis of variance and a paired t-test.Results:Propofol and U83836E significantly ameliorated the CRMP2 proteolysis.In addition,both propofol and U83836E significantly decreased the ratio of 145-kDa αⅡ-spectrin breakdown products to intact 270-kDa spectrin,the 4-hydroxynonenal expression and programmed cell death in the pericontusional cortex at 24 h after TBI.There was no difference between the TBI group and the fat emulsion group.Conclusions:These results demonstrate that propofol postconditioning alleviates calpain-mediated CRMP2 proteolysis and provides neuroprotective effects following moderate TBI potentially by counteracting LP and reducing calpain activation.

  12. Platelet adhesion enhances the glycoprotein VI-dependent procoagulant response: Involvement of p38 MAP kinase and calpain.

    Science.gov (United States)

    Siljander, P; Farndale, R W; Feijge, M A; Comfurius, P; Kos, S; Bevers, E M; Heemskerk, J W

    2001-04-01

    In the final stages of activation, platelets express coagulation-promoting activity by 2 simultaneous processes: exposure of aminophospholipids, eg, phosphatidylserine (PS), at the platelet surface, and formation of membrane blebs, which may be shed as microvesicles. Contact with collagen triggers both processes via platelet glycoprotein VI (GPVI). Here, we studied the capacity of 2 GPVI ligands, collagen-related peptide (CRP) and the snake venom protein convulxin (CVX), to elicit the procoagulant platelet response. In platelets in suspension, either ligand induced full aggregation and high Ca(2+) signals but little microvesiculation or PS exposure. However, most of the platelets adhering to immobilized CRP or CVX had exposed PS and formed membrane blebs after a prolonged increase in cytosolic [Ca(2+)](i). Platelets adhering to fibrinogen responded similarly but only when exposed to soluble CRP or CVX. By scanning electron microscopic analysis, the bleb-forming platelets were detected as either round, spongelike structures with associated microparticles or as arrays of vesicular cell fragments. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) elicited by CRP and CVX was enhanced in fibrinogen-adherent platelets compared with that in platelets in suspension. The p38 inhibitor SB203580 and the calpain protease inhibitor calpeptin reduced only the procoagulant bleb formation, having no effect on PS exposure. Inhibition of p38 also downregulated calpain activity. We conclude that the procoagulant response evoked by GPVI stimulation is potentiated by platelet adhesion. The sequential activation of p38 MAPK and calpain appears to regulate procoagulant membrane blebbing but not PS exposure. PMID:11304481

  13. Calpain 3 is important for muscle regeneration: Evidence from patients with limb girdle muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Hauerslev Simon

    2012-03-01

    Full Text Available Abstract Background Limb girdle muscular dystrophy (LGMD type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was to investigate how mutations in the four functional domains of calpain 3 affect muscle regeneration. Methods We studied muscle regeneration in 22 patients with LGMD2A with calpain 3 deficiency, in five patients with LGMD2I, with a secondary reduction in calpain 3, and in five patients with Becker muscular dystrophy (BMD with normal calpain 3 levels. Regeneration was assessed by using the developmental markers neonatal myosin heavy chain (nMHC, vimentin, MyoD and myogenin and counting internally nucleated fibers. Results We found that the recent regeneration as determined by the number of nMHC/vimentin-positive fibers was greatly diminished in severely affected LGMD2A patients compared to similarly affected patients with LGMD2I and BMD. Whorled fibers, a sign of aberrant regeneration, was highly elevated in patients with a complete lack of calpain 3 compared to patients with residual calpain 3. Regeneration is not affected by location of the mutation in the CAPN3 gene. Conclusions Our findings suggest that calpain 3 is needed for the regenerative process probably during sarcomere remodeling as the complete lack of functional calpain 3 leads to the most severe phenotypes.

  14. Design, syntheses, and conformational study of angiogenesis inhibitors

    International Nuclear Information System (INIS)

    Since anti-angiogensis could lead to the suppression of tumor growth, angiogenesis inhibitors have received particular attention for their therapeutic potential. In this study, two angiogenic inhibitors using the bioactive sequence from the kringle 5, AK1(KLYDY), AK2(KLWDF) were designed and synthesized. We have investigated their solution structures using NMR spectroscopy and their activities as angiogenesis inhibitors. AK2 has an intramolecular hydrogen bond between the side chain amino proton of Lys1 and the carboxy1 oxygen of Asp4 with a N···O distance of 3.27 A, while AK1 shows more flexible structures than AK2. Indole ring in Trp is much bigger than the phenyl ring in Tyr and may have good face-to-edge interaction enforcing more rigid and constrained conformational features of AK2. Because of this relatively stable structure, Trp3 in AK2 may have better hydrophobic interaction with Phe5 than Tyr3 in AK1 if two adjacent aromatic groups are located in hydrophobic pocket of receptor. Since AK2 shows the similar anti-angiogenic activities to AK1, we are also able to confirm that the activity of AK1 is irrelevant to the Tyr phosphorylation. More rigid drug with higher activities can be provided by the mimetic approaches. For the further development of the angiogenesis inhibitors, these conformational studies on our lead peptides will be helpful in design of peptidomimetics

  15. Immunological detection of m- and µ-calpains in the skeletal muscle of Marchigiana cattle

    Directory of Open Access Journals (Sweden)

    E. Varricchio

    2013-01-01

    Full Text Available Calpains are Ca2+-dependent proteases able to cleave a large number of proteins involved in many biological functions. Particularly, in skeletal muscle they are involved in meat tenderizing during post mortem storage. In this report we analyzed the presence and expression of µ- and m-calpains in two skeletal muscles of the Marchigiana cattle soon after slaughter, using immunocytochemical and immunohistochemical techniques, Western blotting analysis and Casein Zymography. Therefore, the presence and the activity of these proteases was investigated until 15th day post-mortem during normal process of meat tenderizing. The results showed m- and µ-calpain immunosignals in the cytoplasm both along the Z disk/I band regions and in the form of intracellular stores. Moreover, the expression level of µ-calpain but not m-calpain decreased after 10 days of storage. Such a decrease in µ-calpain was accompanied by a gradual reduction of activity. On the contrary, m-calpain activity persisted up to 15 days of post-mortem storage. Such data indicate that expression and activity of both µ-calpain and m-calpain analyzed in the Marchigiana cattle persist longer than reported in literature for other bovines and may be related to both the type of muscle and breed examined.

  16. Immunological detection of m- and µ-calpains in the skeletal muscle of Marchigiana cattle

    Science.gov (United States)

    Varricchio, E.; Russolillo, M.G.; Maruccio, L.; Velotto, S.; Campanile, G.; Paolucci, M.; Russo, F.

    2013-01-01

    Calpains are Ca2+-dependent proteases able to cleave a large number of proteins involved in many biological functions. Particularly, in skeletal muscle they are involved in meat tenderizing during post mortem storage. In this report we analyzed the presence and expression of µ- and m-calpains in two skeletal muscles of the Marchigiana cattle soon after slaughter, using immunocytochemical and immunohistochemical techniques, Western blotting analysis and Casein Zymography. Therefore, the presence and the activity of these proteases was investigated until 15th day post mortem during normal process of meat tenderizing. The results showed m- and µ-calpain immunosignals in the cytoplasm both along the Z disk/I band regions and in the form of intracellular stores. Moreover, the expression level of µ-calpain but not m-calpain decreased after 10 days of storage. Such a decrease in µ-calpain was accompanied by a gradual reduction of activity. On the contrary, m-calpain activity persisted up to 15 days of post mortem storage. Such data indicate that expression and activity of both µ-calpain and m-calpain analyzed in the Marchigiana cattle persist longer than reported in literature for other bovines and may be related to both the type of muscle and breed examined. PMID:23549461

  17. The expression of calpain-I in cerebral vasospasm:a preliminary investigation in experimental rabbits

    International Nuclear Information System (INIS)

    Objective: To investigate the expression of calpain-I in rabbit model with cerebral vasospasm and to discuss the clinical significance of calpain-I in cerebral vasospasm. Methods: Twenty-five healthy New Zealand white rabbits were randomly divided into two groups: normal control group (n = 5) and subarachnoid hemorrhage (SAH) group (n = 20). The subarachnoid hemorrhage was created by endovascular punctures. The SAH group, according to the time of sacrifice, was randomly and equally subdivided into 12-hour, 1-day, 3-day, and 7-day subgroups with 5 rabbits in each group. The expressions of calpain-I of the smooth muscles of basilar arteries in both groups were determined by means of immunohistochemistry technique, and the semi-quantitative analysis of calpain-I was evaluated by histochemistry score. Results: The expression of calpain-I was slightly elevated at 12 hours after SAH, it reached to its peak at the third day, and then declined on the seventh day. The semi-quantitative analysis of calpain-I showed that the difference in the expression of calpain-I between two groups was of statistic significance (P < 0.01). Conclusion: After subarachnoid hemorrhage, the expression of calpain-I in the spasmodic smooth muscles of basilar artery is enhanced, and the changes of the expression level is early, gradual and continuous. Most probably, the calpain-I participates in the process of vessel wall structural signal transduction change in cerebral vasospasm. (authors)

  18. Pharmacological inhibition of caspase and calpain proteases: a novel strategy to enhance the homing responses of cord blood HSPCs during expansion.

    Directory of Open Access Journals (Sweden)

    V M Sangeetha

    Full Text Available BACKGROUND: Expansion of hematopoietic stem/progenitor cells (HSPCs is a well-known strategy employed to facilitate the transplantation outcome. We have previously shown that the prevention of apoptosis by the inhibition of cysteine proteases, caspase and calpain played an important role in the expansion and engraftment of cord blood (CB derived HSPCs. We hypothesize that these protease inhibitors might have maneuvered the adhesive and migratory properties of the cells rendering them to be retained in the bone marrow for sustained engraftment. The current study was aimed to investigate the mechanism of the homing responses of CB cells during expansion. METHODOLOGY/PRINCIPAL FINDINGS: CB derived CD34(+ cells were expanded using a combination of growth factors with and without Caspase inhibitor -zVADfmk or Calpain 1 inhibitor- zLLYfmk. The cells were analyzed for the expression of homing-related molecules. In vitro adhesive/migratory interactions and actin polymerization dynamics of HSPCs were assessed. In vivo homing assays were carried out in NOD/SCID mice to corroborate these observations. We observed that the presence of zVADfmk or zLLYfmk (inhibitors caused the functional up regulation of CXCR4, integrins, and adhesion molecules, reflecting in a higher migration and adhesive interactions in vitro. The enhanced actin polymerization and the RhoGTPase protein expression complemented these observations. Furthermore, in vivo experiments showed a significantly enhanced homing to the bone marrow of NOD/SCID mice. CONCLUSION/SIGNIFICANCE: Our present study reveals another novel aspect of the regulation of caspase and calpain proteases in the biology of HSPCs. The priming of the homing responses of the inhibitor-cultured HSPCs compared to the cytokine-graft suggests that the modulation of these proteases may help in overcoming the major homing defects prevalent in the expansion cultures thereby facilitating the manipulation of cells for transplant

  19. Modulation of intracellular calcium levels by calcium lactate affects colon cancer cell motility through calcium-dependent calpain.

    Directory of Open Access Journals (Sweden)

    Pasupathi Sundaramoorthy

    Full Text Available Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+ supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa, its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+ levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain in a dose-dependent manner. Phosphorylated FAK (p-FAK was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer.

  20. Restriction fragment length polymorphism in calpain (CAPN2 gene in crossbred cattle

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Cassiano Lara

    2012-12-01

    Full Text Available With advances in molecular genetics have been possible to predict the genetic value of the animal, in particular its potential to transmit desired characters to their offspring, including characters difficult to evaluate or with low heritability, as is the case of the meat tenderization. It is known that Bos taurus indicus features differences in meat tenderization, being assigned this variability to their lowest proteolysis post-mortem, as result of high activity of calpastatin. This inhibitor decreases the activity of calpain, which are the enzymes responsible for the degradation of muscle fibers during the maturation of the meat. Moreover, there were previously observed differences in the frequencies of allele A of calpain among European breeds (Hereford, Aberdeen Angus and Holstein and Bos taurus indicus (Gir, Guzerá and Nelore. This variability has been related to tenderness of meat, as cattle with Bos taurus taurus origin have more tender meat than Bos taurus indicus, showing small values of shear force. One explanation is that the Capn2A product could confer greater proteolytic activity than the encoded by the allele Capn2B. If allele A is associated with tender meat, it will be possible the early identification of the animals that have the potential to produce meat with qualities that attend the needs of the consumer market, in order to add economic value to the final product of the animal production chain. For this reason, biochemical and genetic studies related to calpain and calpastatin systems have been considered promising for the clarification of the physiological changes that occur in muscle structure during the period post-mortem, whose results have contributed to the improvement of meat quality. The objectives of this study were to investigate the RFLP in calpain (Capn2 gene and its relation with meat tenderization in 252 crossbred (Bos taurus taurus x Bos taurus indicus. The analyses were carried through by PCR-RFLP technique

  1. Involvement of calpain/p35-p25/Cdk5/NMDAR signaling pathway in glutamate-induced neurotoxicity in cultured rat retinal neurons.

    Directory of Open Access Journals (Sweden)

    Yanying Miao

    Full Text Available We investigated possible involvement of a calpain/p35-p25/cyclin-dependent kinase 5 (Cdk5 signaling pathway in modifying NMDA receptors (NMDARs in glutamate-induced injury of cultured rat retinal neurons. Glutamate treatment decreased cell viability and induced cell apoptosis, which was accompanied by an increase in Cdk5 and p-Cdk5(T15 protein levels. The Cdk5 inhibitor roscovitine rescued the cell viability and inhibited the cell apoptosis. In addition, the protein levels of both calpain 2 and calpain-specific alpha-spectrin breakdown products (SBDPs, which are both Ca(2+-dependent, were elevated in glutamate-induced cell injury. The protein levels of Cdk5, p-Cdk5(T15, calpain 2 and SBDPs tended to decline with glutamate treatments of more than 9 h. Furthermore, the elevation of SBDPs was attenuated by either D-APV, a NMDAR antagonist, or CNQX, a non-NMDAR antagonist, but was hardly changed by the inhibitors of intracellular calcium stores dantrolene and xestospongin. Moreover, the Cdk5 co-activator p35 was significantly up-regulated, whereas its cleaved product p25 expression showed a transient increase. Glutamate treatment for less than 9 h also considerably enhanced the ratio of the Cdk5-phosphorylated NMDAR subunit NR2A at Ser1232 site (p-NR2A(S1232 and NR2A (p-NR2A(S1232/NR2A, and caused a translocation of p-NR2A(S1232 from the cytosol to the plasma membrane. The enhanced p-NR2A(S1232 was inhibited by roscovitine, but augmented by over-expression of Cdk5. Calcium imaging experiments further showed that intracellular Ca(2+ concentrations ([Ca(2+](i of retinal cells were steadily increased following glutamate treatments of 2 h, 6 h and 9 h. All these results suggest that the activation of the calpain/p35-p25/Cdk5 signaling pathway may contribute to glutamate neurotoxicity in the retina by up-regulating p-NR2A(S1232 expression.

  2. SwissProt search result: AK104199 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104199 006-304-A08 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prot ... ein) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 3e-11 ...

  3. SwissProt search result: AK104366 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104366 001-035-D07 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prot ... ein) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 3e-11 ...

  4. SwissProt search result: AK107547 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107547 002-130-A05 (Q8BJZ3) Transmembrane BAX inhibitor motif containing protein 1 (RECS1 prot ... ein) (Responsive to centrifugal force ... and shear stress gene 1 protein) TMBI1_MOUSE 1e-14 ...

  5. SwissProt search result: AK059921 [KOME

    Lifescience Database Archive (English)

    Full Text Available ine-specific protein) (NSP) (Neuroendocrine specific protein C homolog) (RTN-x) (Reticulon 5) RTN4_HUMAN 5e-14 ... ...AK059921 006-209-G09 (Q9NQC3) Reticulon-4 (Neurite outgrowth inhibitor) (Nogo protein) (Foocen) (Neuroendocr

  6. SwissProt search result: AK072628 [KOME

    Lifescience Database Archive (English)

    Full Text Available ne-specific protein) (NSP) (Neuroendocrine specific protein C homolog) (RTN-x) (Reticulon 5) RTN4_HUMAN 4e-14 ... ...AK072628 J023130B01 (Q9NQC3) Reticulon-4 (Neurite outgrowth inhibitor) (Nogo protein) (Foocen) (Neuroendocri

  7. SwissProt search result: AK073583 [KOME

    Lifescience Database Archive (English)

    Full Text Available ne-specific protein) (NSP) (Neuroendocrine specific protein C homolog) (RTN-x) (Reticulon 5) RTN4_HUMAN 2e-13 ... ...AK073583 J033051P18 (Q9NQC3) Reticulon-4 (Neurite outgrowth inhibitor) (Nogo protein) (Foocen) (Neuroendocri

  8. SwissProt search result: AK104196 [KOME

    Lifescience Database Archive (English)

    Full Text Available ine-specific protein) (NSP) (Neuroendocrine specific protein C homolog) (RTN-x) (Reticulon 5) RTN4_HUMAN 5e-14 ... ...AK104196 006-303-H05 (Q9NQC3) Reticulon-4 (Neurite outgrowth inhibitor) (Nogo protein) (Foocen) (Neuroendocr

  9. UniProt search blastx result: AK288359 [KOME

    Lifescience Database Archive (English)

    Full Text Available e) (Cellobiase) (Beta-D-glucoside glucohydrolase) (T-cell inhibitor) - Salmonella typhimurium 9.00E-49 ... ...AK288359 J090024N02 Q56078|BGLX_SALTY Periplasmic beta-glucosidase precursor (EC 3.2.1.21) (Gentiobias

  10. SwissProt search result: AK073774 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073774 J033068C19 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-11 ...

  11. SwissProt search result: AK098868 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK098868 J013001A15 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 4e-15 ...

  12. SwissProt search result: AK066162 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066162 J013053H05 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 3e-14 ...

  13. SwissProt search result: AK064280 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064280 002-105-G03 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 9e-13 ...

  14. SwissProt search result: AK061398 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061398 006-305-F03 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 5e-15 ...

  15. SwissProt search result: AK100396 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100396 J023086G18 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-13 ...

  16. SwissProt search result: AK073182 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073182 J033001F09 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 6e-14 ...

  17. SwissProt search result: AK065494 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065494 J013025I12 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 8e-13 ...

  18. SwissProt search result: AK062188 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062188 001-046-E07 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 1e-15 ...

  19. SwissProt search result: AK103003 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103003 J033116G17 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 6e-14 ...

  20. SwissProt search result: AK121819 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121819 J033099B16 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 1e-10 ...

  1. SwissProt search result: AK100142 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100142 J023011I08 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 1e-11 ...

  2. SwissProt search result: AK059381 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059381 001-026-G02 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-13 ...

  3. SwissProt search result: AK240947 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240947 J065043C16 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-11 ...

  4. SwissProt search result: AK101616 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101616 J033052G09 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-15 ...

  5. SwissProt search result: AK102758 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102758 J033107C10 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 3e-14 ...

  6. SwissProt search result: AK109689 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109689 002-145-E02 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-11 ...

  7. SwissProt search result: AK109139 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109139 002-155-E07 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 1e-11 ...

  8. SwissProt search result: AK111977 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111977 001-007-H12 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1. ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 2e-11 ...

  9. SwissProt search result: AK100479 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100479 J023095H24 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 9e-12 ...

  10. SwissProt search result: AK100849 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100849 J023123I07 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 1e-16 ...

  11. SwissProt search result: AK066885 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066885 J013088G18 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 3e-15 ...

  12. SwissProt search result: AK111737 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111737 J023047K02 (Q9VEZ5) Inhibitor of nuclear factor kappa B kinase beta subunit (EC 2.7.1.3 ... ein) (Lipopolysaccharide-activated kinase) (DLAK) (Cactus ... kinase IKK) IKKB_DROME 9e-12 ...

  13. GenBank blastx search result: AK287588 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287588 J065045K19 BT025443.1 BT025443 Bos taurus serpin peptidase inhibitor, clad...e B (ovalbumin), member 1 (SERPINB1), NotI truncated, mRNA, incomplete 3' cds. MAM 4e-21 0 ...

  14. GenBank blastx search result: AK287588 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287588 J065045K19 L20792.1 MOTSERPINB Manduca sexta (clones H5, H10, H14, H17) pu...tative serine proteinase inhibitor (serpin 1, exon 9 copy 2) mRNA, complete cds. INV 1e-19 0 ...

  15. GenBank blastx search result: AK243629 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243629 J100087B22 L20792.1 MOTSERPINB Manduca sexta (clones H5, H10, H14, H17) pu...tative serine proteinase inhibitor (serpin 1, exon 9 copy 2) mRNA, complete cds. INV 6e-29 1 ...

  16. μ- and m-calpain expression and activity changes following diethylstilbestrol injection in the rat anterior pituitary

    Institute of Scientific and Technical Information of China (English)

    Weijiang Zhao; Zhongfang Shi; Fang Yuan; Guilin Li; Yazhuo Zhang; Zhongcheng Wang

    2011-01-01

    Little is known about changes in calpain activity in the pituitary gland.In the present study,μ- and m-calpain activity changes were detected in the rat anterior pituitary following intraperitoneal injection of diethylstilbestrol.Double-immunofluorescence labeling confirmed colocalization of μ - and m-calpain in prolactin-secreting cells (lactotrophs).Western blot analysis revealed significantly increased expression of both calpains,which accompanied upregulated cytosol and membrane zymographic activities at 12 weeks following diethylstilbestrol injection,compared with rats injected with sunflower oil.Moreover,following estrogen injection,pituitary gland pathological damage gradually worsened with increasing time.Results demonstrated that estrogen regulated calpain expression and activity,and both calpains participated in the pathophysiological processes of the pituitary gland.Ubiquitous calpain expression could serve as an effective target for anti-estrogen drugs.

  17. Tissue-Specific Expression of the Chicken Calpain2 Gene

    OpenAIRE

    Qing Zhu; Yi-Ping Liu; Xiao-Cheng Li; Hua-Rui Du; Xiao-Song Jiang; Zeng-Rong Zhang

    2010-01-01

    We quantified chicken calpain 2 (CAPN2) expression in two Chinese chicken breeds (mountainous black-bone chicken breed [MB] and a commercial meat type chicken breed [S01]) to discern the tissue and ontogenic expression pattern and its effect on muscle metabolism. Real-time quantitative PCR assay was developed for accurate measurement of the CAPN2 mRNA expression in various tissues from chickens of different ages (0, 2, 4, 6, 8, 10, and 12 weeks). Results showed that the breast muscle and leg ...

  18. Calpain activity promotes the sealing of severed giant axons

    OpenAIRE

    Godell, Christopher M.; Smyers, Mark E.; Eddleman, Christopher S.; Ballinger, Martis L.; Fishman, Harvey M.; Bittner, George D.

    1997-01-01

    A barrier (seal) must form at the cut ends of a severed axon if a neuron is to survive and eventually regenerate. Following severance of crayfish medial giant axons in physiological saline, vesicles accumulate at the cut end and form a barrier (seal) to ion and dye diffusion. In contrast, squid giant axons do not seal, even though injury-induced vesicles form after axonal transection and accumulate at cut axonal ends. Neither axon seals in Ca2+-free salines. The addition of calpain to the bat...

  19. Effect of protein S-nitrosylation on autolysis and catalytic ability of μ-calpain.

    Science.gov (United States)

    Liu, Rui; Li, Yupin; Wang, Mengqin; Zhou, Guanghong; Zhang, Wangang

    2016-12-15

    The effect of S-nitrosylation on the autolysis and catalytic ability of μ-calpain in vitro in the presence of 50μM Ca(2 +) was investigated. μ-Calpain was incubated with different concentrations of nitric oxide donor S-nitrosoglutathione (GSNO) and subsequently reacted with purified myofibrils. Results showed that the amount of 80kDa μ-calpain subunit significantly decreased as GSNO increased from 0 to 300μM, but increases of GSNO to 300, 500 and 1000μM did not result in further inhibition. The catalytic ability of nitrosylated μ-calpain to degrade titin, nebulin, troponin-T and desmin was significantly reduced when the GSNO concentration was higher than 300μM. The cysteine residues of μ-calpain at positions 49, 351, 384, and 592 in the catalytic subunit and at 142 in small subunit were S-nitrosylated, which could be responsible for decreased μ-calpain activity. Thus, S-nitrosylation can negatively regulate the activation of μ-calpain resulting in decreased proteolytic ability on myofibrils. PMID:27451206

  20. Influence of early pH decline on calpain activity in porcine muscle.

    Science.gov (United States)

    Pomponio, Luigi; Ertbjerg, Per; Karlsson, Anders H; Costa, Leonardo Nanni; Lametsch, René

    2010-05-01

    This study investigated the influence of post-mortem pH decline on calpain activity and myofibrillar degradation. From 80 pigs, 30 Longissimus dorsi (LD) muscles were selected on the basis of pH values at 3h post-mortem and classified into groups of 10 as fast, intermediate and slow pH decline. The rate of pH decline early post-mortem differed between the three groups, but the ultimate pH values were similar at 24h. Calpain activity and autolysis from 1 to 72h post-mortem were determined using casein zymography and studied in relation to myofibrillar fragmentation. Colour and drip loss were measured. A faster decrease in pH resulted in reduced level of mu-calpain activity and increased autolysis of the enzyme, and hence an earlier loss of activity due to activation of mu-calpain in muscles with a fast pH decline. Paralleling the mu-calpain activation in muscles with a fast pH decline a higher myofibril fragmentation at 24h post-mortem was observed, which was no longer evident in the later phase of the tenderization process. In conclusion, the rate of early pH decline influenced mu-calpain activity and the rate but not the extent of myofibrillar degradation, suggesting an early effect of proteolysis on myofibril fragmentation that is reduced during ageing due to an earlier exhaustion of mu-calpain activity. PMID:20374873

  1. Cloning, expression, and polymorphism of the porcine calpain10 gene

    Institute of Scientific and Technical Information of China (English)

    Xiuqin Yang; Di Liu; Hao Yu; Lijuan Guo; Hui Liu

    2008-01-01

    Calpains are calcium-regulated protcases involved in cellular functions that include muscle proteolysis both ante- and postmortem. This study was designed to clone the complete coding sequence of the porcine calpain10 gene, CAPN10, to analyze its expression characteristics and to investigate its polymorphism. Two isoforms of the CAPN10 gene, CAPN10A and CAPN10B, were obtained by reverse transcriptionpolymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends methods combined with in silico cloning. RT-PCR results indicated that CAPN10 mRNA was ubiquitously expressed in all tissues examined and, with increasing age,the expression level increased in muscles at six different growth points. In the same tissues, the expression level of CAPN10A was higher than that of CAPN10B. In addition,three single nucleotide polymorphisms were detected by the PCR-single-stranded conformational polymorphism method and by comparing the sequences of Chinese Min pigs with those of Yorkshire pigs. C527T mutation was a missense mutation and led to transforming Pro into Leu at the 176th amino acid. The results of the current study provided basic molecular information for further study of the function of the porcine CAPN10 gene.

  2. Calpain system and its involvement in myocardial ischemia and reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Christiane; Neuhof; Heinz; Neuhof

    2014-01-01

    Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia,reperfusion and postischemic structural remodelling.The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains.Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria.Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria.Calpain inhibition can prevent or attenuate myocardial injury during ischemia,reperfusion,and in later stages of myocardial infarction.

  3. Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Hasseldam, Henrik; Rasmussen, Rune Skovgaard;

    2014-01-01

    necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved α-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9 cleavage, μ-calpain upregulation and cleaved α-spectrin...... of μ-calpain, a calpain-produced necrosis-related casp-9 fragment (25kDa) and cleavage of α-spectrin into 145/150kDa fragments at day 4, whereas in ischemia-only animals a significant increase of casp-3-cleaved PARP, cleavage of α-spectrin into 145/150 and 120kDa fragments was detected at day 7. We...

  4. Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer’s disease brain

    OpenAIRE

    Kurbatskaya, Ksenia; Phillips, Emma Claire; Croft, Cara Louise; Dentoni, Giacomo; Hughes, Martina; Wade, Matthew Austen James; Al-Sarraj, Safa; Troakes, Claire; O'Neill, Michael; Gomez Perez-Nievas, Beatriz; Hanger, Diane Pamela; Noble, Wendy Jane

    2016-01-01

    Alterations in calcium homeostasis are widely reported to contribute to synaptic degeneration and neuronal loss in Alzheimer’s disease. Elevated cytosolic calcium concentrations lead to activation of the calcium-sensitive cysteine protease, calpain, which has a number of substrates known to be abnormally regulated in disease. Analysis of human brain has shown that calpain activity is elevated in AD compared to controls, and that calpain-mediated proteolysis regulates the activity of important...

  5. Loss of Calpain 3 Proteolytic Activity Leads to Muscular Dystrophy and to Apoptosis-Associated Iκbα/Nuclear Factor κb Pathway Perturbation in Mice

    OpenAIRE

    RICHARD, Isabelle; Roudaut, Carinne; Marchand, Sylvie; Baghdiguian, Stephen; Herasse, Muriel; Stockholm, Daniel; Ono, Yasuko; Suel, Laurence; Bourg, Nathalie; Sorimachi, Hiroyuki; Lefranc, Gérard; Fardeau, Michel; Sébille, Alain; Beckmann, Jacques S.

    2000-01-01

    Calpain 3 is known as the skeletal muscle–specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. It was previously shown that defects in the human calpain 3 gene are responsible for limb girdle muscular dystrophy type 2A (LGMD2A), an inherited disease affecting predominantly the proximal limb muscles. To better understand the function of calpain 3 and the pathophysiological mechanisms of LGMD2A and also to develop an adequate model for therapy research, we...

  6. Calpain-Calcineurin-Nuclear Factor Signaling and the Development of Atrial Fibrillation in Patients with Valvular Heart Disease and Diabetes

    Science.gov (United States)

    Zhao, Yong; Cui, Guo-ming; Zhou, Nan-nan; Li, Cong; Zhang, Qing; Sun, Hui; Han, Bo; Zou, Cheng-wei; Wang, Li-juan; Li, Xiao-dong; Wang, Jian-chun

    2016-01-01

    Calpain, calcineurin (CaN), and nuclear factor of activated T cell (NFAT) play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD) are prone to develop atrial fibrillation (AF). Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha- and beta-isoforms of CaN catalytic subunit (CnA) as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR). Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes. PMID:27123462

  7. Mechanical stimulation of C2C12 cells increases m-calpain expression, focal adhesion plaque protein degradation

    DEFF Research Database (Denmark)

    Grossi, Alberto; Karlsson, Anders H; Lawson, Moira Ann

    2008-01-01

    reorganization due to the activity of the ubiquitous proteolytic enzymes, calpains, has been reported. Whether there is a link between stretch- or load-induced signaling and calpain expression and activation is not known. Using a magnetic bead stimulation assay and C2C12 mouse myoblasts cell population, we have...

  8. Mechanical stimuli activation of calpain is required for myoblast differentiation and occurs via an ERK/MAP kinase signaling pathway

    DEFF Research Database (Denmark)

    Grossi, Alberto; Karlsson, Anders H; Lawson, Moira Ann

    fusion, cell membrane and cytoskeleton component reorganization due to the activity of ubiquitous proteolytic enzymes known as calpains has been reported. Whether there is a link between stretch- or load induced signals, the MAPK pathway and calpain expression and activation is not known. Using a...

  9. Product annotations: AK241310 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241310 J065141C01 BLASTN AY090534.1 PLN AY090534 Deschampsia antarctica plastid-specific... ribosomal protein 2 precursor, mRNA, partial cds; nuclear gene for plastid product. 8e-78 ...

  10. Product annotations: AK062461 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062461 001-103-D08 BLASTN AY090534 PLN Deschampsia antarctica plastid-specific ri...bosomal protein 2 precursor, mRNA, partial cds; nuclear gene for plastid product.|PLN 1e-78 ...

  11. Product annotations: AK104715 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104715 001-038-A04 BLASTN AY090534 PLN Deschampsia antarctica plastid-specific ri...bosomal protein 2 precursor, mRNA, partial cds; nuclear gene for plastid product.|PLN 2e-78 ...

  12. 46 CFR 7.165 - Kenai Peninsula, AK to Kodiak Island, AK.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Kenai Peninsula, AK to Kodiak Island, AK. 7.165 Section... BOUNDARY LINES Alaska § 7.165 Kenai Peninsula, AK to Kodiak Island, AK. (a) A line drawn from the southernmost extremity of Kenai Peninsula at longitude 151°44.0′ W. to East Amatuli Island Light; thence to...

  13. The Prediction of Calpain Cleavage Sites with the mRMR and IFS Approaches

    Directory of Open Access Journals (Sweden)

    Wenyi Zhang

    2013-01-01

    Full Text Available Calpains are an important family of the Ca2+-dependent cysteine proteases which catalyze the limited proteolysis of many specific substrates. Calpains play crucial roles in basic physiological and pathological processes, and identification of the calpain cleavage sites may facilitate the understanding of the molecular mechanisms and biological function. But traditional experiment approaches to predict the sites are accurate, and are always labor-intensive and time-consuming. Thus, it is common to see that computational methods receive increasing attention due to their convenience and fast speed in recent years. In this study, we develop a new predictor based on the support vector machine (SVM with the maximum relevance minimum redundancy (mRMR method followed by incremental feature selection (IFS. And we concern the feature of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure, and solvent accessibility to represent the calpain cleavage sites. Experimental results show that the performance of our predictor is better than several other state-of- the-art predictors, whose average prediction accuracy is 79.49%, sensitivity is 62.31%, and specificity is 88.12%. Since user-friendly and publicly accessible web servers represent the future direction for developing practically more useful predictors, here we have provided a web-server for the method presented in this paper.

  14. Association of the calpain-10 gene with type 2 diabetes in Europeans

    DEFF Research Database (Denmark)

    Tsuchiya, Takafumi; Schwarz, Peter E H; Bosque-Plata, Laura Del; Geoffrey Hayes, M; Dina, Christian; Froguel, Philippe; Wayne Towers, G; Fischer, Sabine; Temelkova-Kurktschiev, Theodora; Rietzsch, Hannes; Graessler, Juergen; Vcelák, Josef; Palyzová, Daniela; Selisko, Thomas; Bendlová, Bela; Schulze, Jan; Julius, Ulrich; Hanefeld, Markolf; Weedon, Michael N; Evans, Julie C; Frayling, Timothy M; Hattersley, Andrew T; Orho-Melander, Marju; Groop, Leif; Malecki, Maciej T; Hansen, Torben; Pedersen, Oluf; Fingerlin, Tasha E; Boehnke, Michael; Hanis, Craig L; Cox, Nancy J; Bell, Graeme I

    We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele ...

  15. Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

    Directory of Open Access Journals (Sweden)

    Storr Sarah J

    2012-11-01

    Full Text Available Abstract Background Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036, and between nuclear calpastatin expression and increased tumour stage (P = 0.026 and the presence of vascular invasion (P = 0.043. In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036, which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007. In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012, which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037. Conclusion The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study.

  16. Calpain 2-mediated autophagy defect increases susceptibility of fatty livers to ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Q; Guo, Z; Deng, W; Fu, S; Zhang, C; Chen, M; Ju, W; Wang, D; He, X

    2016-01-01

    Hepatic steatosis is associated with significant morbidity and mortality after liver resection and transplantation. This study focuses on the role of autophagy in regulating sensitivity of fatty livers to ischemia and reperfusion (I/R) injury. Quantitative immunohistochemistry conducted on human liver allograft biopsies showed that, the reduction of autophagy markers LC3 and Beclin-1 at 1 h after reperfusion, was correlated with hepatic steatosis and poor survival of liver transplant recipients. In animal studies, western blotting and confocal imaging analysis associated the increase in sensitivity to I/R injury with low autophagy activity in fatty livers. Screening of autophagy-related proteins showed that Atg3 and Atg7 expression levels were marked decreased, whereas calpain 2 expression was upregulated during I/R in fatty livers. Calpain 2 inhibition or knockdown enhanced autophagy and suppressed cell death. Further point mutation experiments revealed that calpain 2 cleaved Atg3 and Atg7 at Atg3Δ92-97 and Atg7Δ344-349, respectively. In vivo and in vitro overexpression of Atg3 or Atg7 enhanced autophagy and suppressed cell death after I/R in fatty livers. Collectively, calpain 2-mediated degradation of Atg3 and Atg7 in fatty livers increases their sensitivity to I/R injury. Increasing autophagy may ameliorate fatty liver damage and represent a valuable method to expand the liver donor pool. PMID:27077802

  17. Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

    International Nuclear Information System (INIS)

    Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study

  18. Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation.

    Science.gov (United States)

    Boehmerle, Wolfgang; Zhang, Kun; Sivula, Michael; Heidrich, Felix M; Lee, Yashang; Jordt, Sven-Eric; Ehrlich, Barbara E

    2007-06-26

    Paclitaxel (Taxol) is a well established chemotherapeutic agent for the treatment of solid tumors, but it is limited in its usefulness by the frequent induction of peripheral neuropathy. We found that prolonged exposure of a neuroblastoma cell line and primary rat dorsal root ganglia with therapeutic concentrations of Taxol leads to a reduction in inositol trisphosphate (InsP(3))-mediated Ca(2+) signaling. We also observed a Taxol-specific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP(3) receptor (InsP(3)R) activity. This reduction was also found in peripheral neuronal tissue from Taxol treated animals. We further observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide-mediated Ca(2+) signaling. When NCS-1 protein levels recovered, so did InsP(3)-mediated Ca(2+) signaling. Inhibition of the Ca(2+)-activated protease mu-calpain prevented alterations in phosphoinositide-mediated Ca(2+) signaling and NCS-1 protein levels. We also found that NCS-1 is readily degraded by mu-calpain in vitro and that mu-calpain activity is increased in Taxol but not vehicle-treated cells. From these results, we conclude that prolonged exposure to Taxol activates mu-calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP(3)mediated Ca(2+) signaling. These findings provide a previously undescribed approach to understanding and treating Taxol-induced peripheral neuropathy. PMID:17581879

  19. Growth and development of skeletal muscle in µ-Calpain Knockout mice

    Science.gov (United States)

    Protein turnover ultimately requires proteolytic enzymes to degrade skeletal muscle proteins. The calpain system has been identified as a potential candidate due to its role in a variety of cellular processes such as cytoskeletal remodeling, myogenesis and signal transduction; and involvement in mu...

  20. Significant role of μ-calpain (CANP1) in proliferation/survival of bovine skeletal muscle satellite cells

    OpenAIRE

    Ba, Hoa Van; Inho, Hwang

    2013-01-01

    Calpains are a family of Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed μ-calpain (CANP1) and m-calpain (CANP2). The CANP1 has been found to play a central role in postmortem proteolysis and meat tenderization. However, the physiological roles of CANP1 in cattle skeletal satellite cells remain unclear. In this study, three small interference RNA sequences (siRNAs) targeting CANP1 gene were designed and ligated into pSilencer plasmid vector to construct s...

  1. Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sang Koo Lee

    2008-01-01

    Full Text Available Aspirin and other nonsteroidal anti-inflammatory drugs show efficacy in the prevention of cancers. It is known that they can inhibit cyclooxygenases, and some studies have shown that they can induce apoptosis. Our objective in this study was to investigate the mechanism by which aspirin exerts its apoptosis effects in human cervical cancer HeLa cells. The effect of aspirin on the gene expression was studied by differential mRNA display RT-PCR. Among the isolated genes, mu-type calpain gene was upregulated by aspirin treatment. To examine whether calpain mediates the antitumor effects, HeLa cells were stably transfected with the mammalian expression vector pCR3.1 containing mu-type calpain cDNA (pCRCAL/HeLa, and tumor formations were measured in nude mice. When tumor burden was measured by day 49, HeLa cells and pCR/HeLa cells (vector control produced tumors of 2126 mm3 and 1638 mm3, respectively, while pCRCAL/HeLa cells produced markedly smaller tumor of 434 mm3 in volume. The caspase-3 activity was markedly elevated in pCRCAL/HeLa cells. The increased activity levels of caspase-3 in pCRCAL/HeLa cells, in parallel with the decreased tumor formation, suggest a correlation between caspase-3 activity and calpain protein. Therefore, we conclude that aspirin-induced calpain mediates an antitumor effect via caspase-3 in cervical cancer cells.

  2. Reactive protoplasmic and fibrous astrocytes contain high levels of calpain-cleaved alpha 2 spectrin.

    Science.gov (United States)

    Kim, Jung H; Kwon, Soojung J; Stankewich, Michael C; Huh, Gi-Yeong; Glantz, Susan B; Morrow, Jon S

    2016-02-01

    Calpain, a family of calcium-dependent neutral proteases, plays important roles in neurophysiology and pathology through the proteolytic modification of cytoskeletal proteins, receptors and kinases. Alpha 2 spectrin (αII spectrin) is a major substrate for this protease family, and the presence of the αII spectrin breakdown product (αΙΙ spectrin BDP) in a cell is evidence of calpain activity triggered by enhanced intracytoplasmic Ca(2+) concentrations. Astrocytes, the most dynamic CNS cells, respond to micro-environmental changes or noxious stimuli by elevating intracytoplasmic Ca(2+) concentration to become activated. As one measure of whether calpains are involved with reactive glial transformation, we examined paraffin sections of the human cerebral cortex and white matter by immunohistochemistry with an antibody specific for the calpain-mediated αΙΙ spectrin BDP. We also performed conventional double immunohistochemistry as well as immunofluorescent studies utilizing antibodies against αΙΙ spectrin BDP as well as glial fibrillary acidic protein (GFAP). We found strong immunopositivity in selected protoplasmic and fibrous astrocytes, and in transitional forms that raise the possibility of some of fibrous astrocytes emerging from protoplasmic astrocytes. Immunoreactive astrocytes were numerous in brain sections from cases with severe cardiac and/or respiratory diseases in the current study as opposed to our previous study of cases without significant clinical conditions that failed to reveal such remarkable immunohistochemical alterations. Our study suggests that astrocytes become αΙΙ spectrin BDP immunopositive in various stages of activation, and that spectrin cleavage product persists even in fully reactive astrocytes. Immunohistochemistry for αΙΙ spectrin BDP thus marks reactive astrocytes, and highlights the likelihood that calpains and their proteolytic processing of spectrin participate in the morphologic and physiologic transition from

  3. A New Insight into the Role of Calpains in Post-mortem Meat Tenderization in Domestic Animals: A review

    OpenAIRE

    Lian, Ting; Wang, Linjie; Liu, Yiping

    2013-01-01

    Tenderness is the most important meat quality trait, which is determined by intracellular environment and extracellular matrix. Particularly, specific protein degradation and protein modification can disrupt the architecture and integrity of muscle cells so that improves the meat tenderness. Endogenous proteolytic systems are responsible for modifying proteinases as well as the meat tenderization. Abundant evidence has testified that calpains (CAPNs) including calpain I (CAPN1) and calpastati...

  4. Calcium Dysregulation Induces Apoptosis-inducing Factor Release: Cross-talk Between PARP-1- and Calpain- Signaling Pathways

    OpenAIRE

    Vosler, Peter S.; Sun, Dandan; Wang, Suping; Gao, Yanqin; Kintner, Douglas B.; Signore, Armando P.; Cao, Guodong; Chen, Jun

    2009-01-01

    Recent discoveries show that caspase-independent cell death pathways are a pervasive mechanism in neurodegenerative diseases, and apoptosis-inducing factor (AIF) is an important effector of this mode of neuronal death. There are currently two known mechanisms underlying AIF release following excitotoxic stress, PARP-1 and calpain. To test whether there is an interaction between PARP-1 and calpain in triggering AIF release, we used the NMDA toxicity model in rat primary cortical neurons. Expos...

  5. GenBank blastx search result: AK104731 [KOME

    Lifescience Database Archive (English)

    Full Text Available s the 3' end of the C20orf121 gene for chromosome 20 open reading frame 121, the TDE1 gene for t...ma, the 3' end of the ADA gene for adenosine deaminase and two CpG islands, complete sequence.|PRI PRI 2e-32 +1 ... ...AK104731 001-038-C07 Z97053.2 Human DNA sequence from clone RP1-179M20 on chromosome 20 Contain...umour differentially expressed 1, the PKIG gene for protein kinase (cAMP-dependent, catalytic) inhibitor gam

  6. GenBank blastx search result: AK106174 [KOME

    Lifescience Database Archive (English)

    Full Text Available s the 3' end of the C20orf121 gene for chromosome 20 open reading frame 121, the TDE1 gene for t...ma, the 3' end of the ADA gene for adenosine deaminase and two CpG islands, complete sequence.|PRI PRI 2e-32 +1 ... ...AK106174 001-208-C06 Z97053.2 Human DNA sequence from clone RP1-179M20 on chromosome 20 Contain...umour differentially expressed 1, the PKIG gene for protein kinase (cAMP-dependent, catalytic) inhibitor gam

  7. GenBank blastx search result: AK063591 [KOME

    Lifescience Database Archive (English)

    Full Text Available s the 3' end of the C20orf121 gene for chromosome 20 open reading frame 121, the TDE1 gene for t...ma, the 3' end of the ADA gene for adenosine deaminase and two CpG islands, complete sequence.|PRI PRI 3e-24 +2 ... ...AK063591 001-118-A12 Z97053.2 Human DNA sequence from clone RP1-179M20 on chromosome 20 Contain...umour differentially expressed 1, the PKIG gene for protein kinase (cAMP-dependent, catalytic) inhibitor gam

  8. GenBank blastx search result: AK119191 [KOME

    Lifescience Database Archive (English)

    Full Text Available s the 3' end of the C20orf121 gene for chromosome 20 open reading frame 121, the TDE1 gene for t...ma, the 3' end of the ADA gene for adenosine deaminase and two CpG islands, complete sequence.|PRI PRI 2e-32 +3 ... ...AK119191 001-039-H03 Z97053.2 Human DNA sequence from clone RP1-179M20 on chromosome 20 Contain...umour differentially expressed 1, the PKIG gene for protein kinase (cAMP-dependent, catalytic) inhibitor gam

  9. Calpain-1 Regulation of Matrix Metalloprotease 2 Activity in Vascular Smooth Muscle Cells Facilitates age-associated aortic wall Calcification and Fibrosis

    OpenAIRE

    Jiang, Liqun; Zhang, Jing; Monticone, Robert E.; Telljohann, Richard; Wu, James; Wang, Mingyi; Lakatta, Edward G.

    2012-01-01

    Age-associated central arterial wall stiffness is linked to extracellular matrix (ECM) remodeling, including fibrosis and vascular calcification. Angiotensin II induces both matrix metalloproteinase type 2 (MMP2) and calpain-1 expression and activity in the arterial wall. But the role of calpain-1 in MMP2 activation and ECM remodeling remains unknown. Dual histo-immunolabeling demonstrates co-localization of calpain-1 and MMP2 within old rat vascular smooth muscle cells. Over-expression of ca...

  10. Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand

    Energy Technology Data Exchange (ETDEWEB)

    Partha, Sarathy K.; Ravulapalli, Ravikiran; Allingham, John S.; Campbell, Robert L.; Davies, Peter L. [Queens

    2014-08-21

    Calpains are Ca2+dependent intracellular cysteine proteases that cleave a wide range of protein substrates to help implement Ca2+ signaling in the cell. The major isoforms of this enzyme family, calpain-1 and calpain-2, are heterodimers of a large and a small subunit, with the main dimer interface being formed through their C-terminal penta-EF hand (PEF) domains. Calpain-3, or p94, is a skeletal muscle-specific isoform that is genetically linked to limb-girdle muscular dystrophy. Biophysical and modeling studies with the PEF domain of calpain-3 support the suggestion that full-length calpain-3 exists as a homodimer. Here, we report the crystallization of calpain-3's PEF domain and its crystal structure in the presence of Ca2+, which provides evidence for the homodimer architecture of calpain-3 and supports the molecular model that places a protease core at either end of the elongated dimer. Unlike other calpain PEF domain structures, the calpain-3 PEF domain contains a Ca2+ bound at the EF5-hand used for homodimer association. Three of the four Ca2+-binding EF-hands of the PEF domains are concentrated near the protease core, and have the potential to radically change the local charge within the dimer during Ca2+ signaling. Examination of the homodimer interface shows that there would be steric clashes if the calpain-3 large subunit were to try to pair with a calpain small subunit.

  11. Product annotations: AK288897 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288897 J090080G08 BLASTN BD354173.1 PAT BD354173 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 5e-83 ...

  12. Product annotations: AK288848 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288848 J090075F08 BLASTN BD354173.1 PAT BD354173 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 3e-38 ...

  13. Product annotations: AK288925 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288925 J090082B10 BLASTN BD354172.1 PAT BD354172 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 2e-13 ...

  14. Product annotations: AK288871 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288871 J090078G09 BLASTN BD354173.1 PAT BD354173 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 6e-96 ...

  15. Product annotations: AK288372 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288372 J090026F05 BLASTN BD354173.1 PAT BD354173 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 1e-69 ...

  16. Product annotations: AK288766 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288766 J090067H02 BLASTN BD354173.1 PAT BD354173 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 7e-41 ...

  17. Product annotations: AK288996 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288996 J090088B05 BLASTN BD354173.1 PAT BD354173 A method for genotyping the peri...pheral region of plant sd-1 gene, and a method for examining semidwarfism of plants using the method. 3e-25 ...

  18. Product annotations: AK318575 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK318575 J090046B04 BLASTX AY542687.1 PLN AY542687 Vitis vinifera merlot proline-rich protein 2 ... (MPRP2) gene, promoter region ... and complete cds; and merlot ripening induced prot ... ein 1 (mrip1) gene, promoter region . 0.0 ...

  19. Product annotations: AK105764 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105764 001-202-D12 BLASTN AY831390 PLN Oryza sativa (indica cultivar-group) BTH-induced protei ... n phosphatase 2C 2 K2 ... form (BIPP2C2) mRNA, complete cds, alternatively s ...

  20. Product annotations: AK289131 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK289131 J090098P07 BLASTX AY823307.1 VRL AY823307 Norovirus swine/GII/OH-QW218/03/...US RNA-dependent RNA polymerase gene, partial cds; and capsid protein and VP2 small basic protein genes, complete cds. 0.0 ...

  1. Genetic disruption of calpain correlates with loss of membrane blebbing and differential expression of RhoGDI-1, cofilin and tropomyosin

    DEFF Research Database (Denmark)

    Larsen, Anna Karina; Lametsch, Rene; Elce, John S.;

    2008-01-01

    cleavage of focal adhesion components and signalling molecules. In this study, the live-cell morphology of calpain-knockout and wild type cells was examined by time-lapse fluorescence microscopy and a role of calpain in mediating formation of sporadic membrane blebs was established. Membrane blebbing was...... role of calpain in regulating membrane extensions involving these proteins. RhoGDI, cofilin and tropomyosin are known regulators of actin filament dymamics and membrane extensions. The reduced levels of RhoGDI-1 in calpain-knockout cells observed by proteome analysis were confirmed by immunoblotting...

  2. Stable expression of calpain 3 from a muscle transgene in vivo: Immature muscle in transgenic mice suggests a role for calpain 3 in muscle maturation

    OpenAIRE

    Spencer, M.J.; Guyon, J. R.; Sorimachi, H.; Potts, A; Richard, I.; Herasse, M; Chamberlain, J.; Dalkilic, I.; Kunkel, L. M.; Beckmann, J S

    2002-01-01

    Limb-girdle muscular dystrophy, type 2A (LGMD 2A), is an autosomal recessive disorder that causes late-onset muscle-wasting, and is due to mutations in the muscle-specific protease calpain 3 (C3). Although LGMD 2A would be a feasible candidate for gene therapy, the reported instability of C3 in vitro raised questions about the potential of obtaining a stable, high-level expression of C3 from a transgene in vivo. We have generated transgenic (Tg) mice with muscle-specific overexpression of ful...

  3. Carcass characteristics, the calpain proteinase system, and aged tenderness of Angus and Brahman crossbred steers.

    Science.gov (United States)

    Pringle, T D; Williams, S E; Lamb, B S; Johnson, D D; West, R L

    1997-11-01

    We used 69 steers of varying percentage Brahman (B) breeding (0% B, n = 11; 25% B, n = 13; 37% B, n = 10; 50% B, n = 12; 75% B, n = 12; 100% B, n = 11) to study the relationship between carcass traits, the calpain proteinase system, and aged meat tenderness in intermediate B crosses. Calpains and calpastatin activities were determined on fresh longissimus muscle samples using anion-exchange chromatography. The USDA yield and quality grade data (24 h) were collected for each carcass. Longissimus steaks were removed and aged for 5 or 14 d for determination of shear force and 5 d for sensory panel evaluation. Even though some yield grade factors were affected by the percentage of B breeding, USDA yield grades did not differ (P > .15) between breed types. Marbling score and USDA quality grade decreased linearly (P Brahman crosses. PMID:9374310

  4. Calpain and cathepsin activities in post mortem fish and meat muscles

    OpenAIRE

    Cheret, Romuald; Delbarre Ladrat, Christine; De Lamballerie Anton, Marie; VERREZ-BAGNIS Veronique

    2007-01-01

    Post mortem tenderization is one of the most unfavourable quality changes in fish muscle and this contrasts with muscle of mammalian meats. The tenderization can be partly attributed to the acid lysosomal cathepsins and cytosolic neutral calcium-activated calpains. In this study, these proteases from fish and bovine muscles were quantified and compared. The cathepsin B and L activities were in more important amounts in sea bass white muscle than in bovine muscle. On the other hand, cathepsin ...

  5. Tear me down: Role of calpain in the development of cardiac ventricular hypertrophy

    OpenAIRE

    Patterson, Cam; Portbury, Andrea; Schisler, Jonathan C; Willis, Monte S.

    2011-01-01

    Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize...

  6. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  7. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    International Nuclear Information System (INIS)

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  8. Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyunho [Transplantation Research Institute, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Department of Medicine, University of Maryland, Baltimore, MD (United States); Kang, Ah-Young [Transplantation Research Institute, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Department of Medicine, Program of Immunology, Graduate School, Seoul National University, Seoul (Korea, Republic of); Ko, Ah-ra [Clinical Research Center, Samsung Biomedical Research Institute, Seoul (Korea, Republic of); Park, Hayne Cho [Transplantation Research Institute, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul (Korea, Republic of); So, Insuk [Department of Physiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of); Cheong, Hae Il [Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Pediatrics, Seoul National University Children’s Hospital, Seoul (Korea, Republic of); Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hwang, Young-Hwan [Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Internal Medicine, Eulji General Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of); and others

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration. - Highlights: • Polycystin-1 is a target of ubiquitin-independent degradation by calpains. • The PEST domain is required for calpain-mediated degradation of polycystin-1. • Polycystin-1 may independently regulate JAK2 and ERK signaling pathways.

  9. Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

    International Nuclear Information System (INIS)

    Autosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration. - Highlights: • Polycystin-1 is a target of ubiquitin-independent degradation by calpains. • The PEST domain is required for calpain-mediated degradation of polycystin-1. • Polycystin-1 may independently regulate JAK2 and ERK signaling pathways

  10. Expression of the gene for large subunit of m-calpain is elevated in skeletal muscle from Duchenne muscular dystrophy patients

    Indian Academy of Sciences (India)

    Tajamul Hussain; Harleen Mangath; C. Sundaram; M. P. J. S. Anandaraj

    2000-08-01

    Calpain is an intracellular nonlysosomal protease involved in essential regulatory or processing functions of the cell, mediated by physiological concentrations of Ca2+. However, in an environment of abnormal intracellular calcium, such as that seen in Duchenne muscular dystrophy (DMD), calpain is suggested to cause degeneration of muscle owing to enhanced activity. To test whether the reported increase in calpain activity in DMD results from de novo synthesis of the protease, we have assessed the quantitative changes in mRNA specific for m-calpain. mRNA isolated from DMD and control muscle was analysed by dot blot hybridization using a cDNA probe for the large subunit of m-calpain. Compared to control a four-fold increase in specific mRNAwas observed in dystrophic muscle. This enhanced expression of the m-calpain gene in dystrophic condition suggests that the reported increase in m-calpain activity results from de novo synthesis of protease and underlines the important role of m-calpain in DMD.

  11. Mechanical Stimulation of C2C12 Cells Increases m-Calpain Expression and Activity, Focal Adhesion Plaque Degradation and Cell Fusion

    DEFF Research Database (Denmark)

    Grossi, Alberto; Lawson, Moira Ann; Karlsson, Anders H

    reorganization due to the activity of ubiquitous proteolytic enzymes known as calpains has been reported. Whether there is a link between stretch- or load induced signaling and calpain expression and activation is not known. Using a magnetic bead stimulation assay and C2C12 mouse myoblasts cell population, we...

  12. Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array.

    Science.gov (United States)

    Shinkai-Ouchi, Fumiko; Koyama, Suguru; Ono, Yasuko; Hata, Shoji; Ojima, Koichi; Shindo, Mayumi; duVerle, David; Ueno, Mika; Kitamura, Fujiko; Doi, Naoko; Takigawa, Ichigaku; Mamitsuka, Hiroshi; Sorimachi, Hiroyuki

    2016-04-01

    Calpains are intracellular Ca(2+)-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis. Thus, it is critically important to determine the site(s) in proteins at which calpains cleave. However, the calpains' substrate specificity remains unclear, because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains' substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10' of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. Thekcat/Kms for 119 sites ranged from 12.5-1,710 M(-1)s(-1) Although most sites were cleaved by both calpain-1 and -2 with a similarkcat/Km, sequence comparisons revealed distinct aa preferences at P9-P7/P2/P5'. The aa compositions of the novel sites were not statistically different from those of previously reported sites as a whole, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is because of substrates' higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) were preferred for proteolysis over C-terminal (P'-sites). Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achievedkcat/Kmprediction withr= 0.834, and binary-QSAR modeling attained an 87.5% positive prediction value for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3', and P4' sites, and P1-P2 cooperativity. Furthermore, using our binary-QSAR model

  13. Zilpaterol hydrochloride improves beef yield, changes palatability traits, and increases calpain-calpastatin gene expression in Nellore heifers.

    Science.gov (United States)

    Cônsolo, Nara Regina Brandão; Ferrari, Viviane Borba; Mesquita, Ligia Garcia; Goulart, Rodrigo Silva; Silva, Luis Felipe Prada E

    2016-11-01

    This research aimed to evaluate the effects of the beta-agonist zilpaterol hydrochloride (ZH) on carcass traits, subprimal yield, meat quality, palatability traits, and gene expression in Nellore heifers. Zilpaterol increased Longissimus lumborum area and did not change back fat thickness, meat color, and cooking loss. Heifers fed ZH had greater hindquarter weight and carcass percentage. Muscles from hindquarter were heavier for animals fed ZH. Forequarter (% of carcass) decreased and brisket did not change with ZH supplementation. There were no differences between treatments for steak aroma, beef flavor, and off-flavor. However, tenderness and juiciness were reduced by ZH, depending on postmortem aging. Zilpaterol increased Calpain-1, Calpain-2, and calpastatin mRNA expression, with no effect of day of slaughter or ZH×Day interaction. In conclusion, ZH supplementation improved hypertrophy, meat production, and debone yield in Nellore heifers, which led to decreased tenderness and to increased mRNA expression in the calpain-calpastatin system. PMID:27427783

  14. Calpains are involved in asexual and sexual development, cell wall integrity and pathogenicity of the rice blast fungus.

    Science.gov (United States)

    Liu, Xiao-Hong; Ning, Guo-Ao; Huang, Lu-Yao; Zhao, Ya-Hui; Dong, Bo; Lu, Jian-Ping; Lin, Fu-Cheng

    2016-01-01

    Calpains are ubiquitous and well-conserved proteins that belong to the calcium-dependent, non-lysosomal cysteine protease family. In this study, 8 putative calpains were identified using Pfam domain analysis and BlastP searches in M. oryzae. Three single gene deletion mutants (ΔMocapn7, ΔMocapn9 and ΔMocapn14) and two double gene deletion mutants (ΔMocapn4ΔMocapn7 and ΔMocapn9ΔMocapn7) were obtained using the high-throughput gene knockout system. The calpain disruption mutants showed defects in colony characteristics, conidiation, sexual reproduction and cell wall integrity. The mycelia of the ΔMocapn7, ΔMocapn4ΔMocapn7 and ΔMocapn9ΔMocapn7 mutants showed reduced pathogenicity on rice and barley. PMID:27502542

  15. Proteolytic degradation of nitric oxide synthase isoforms by calpain is modulated by the expression levels of HSP90.

    Science.gov (United States)

    Averna, Monica; Stifanese, Roberto; De Tullio, Roberta; Salamino, Franca; Bertuccio, Mara; Pontremoli, Sandro; Melloni, Edon

    2007-12-01

    Ca2+ loading of Jurkat and bovine aorta endothelium cells induces the degradation of the neuronal and endothelial nitric oxide synthases that are selectively expressed in these cell lines. For neuronal nitric oxide synthase, this process involves a conservative limited proteolysis without appreciable loss of catalytic activity. By contrast, endothelial nitic oxide synthase digestion proceeds through a parallel loss of protein and catalytic activity. The chaperone heat shock protein 90 (HSP90) is present in a large amount in Jurkat cells and at significantly lower levels in bovine aorta endothelium cells. The differing ratios of HSP90/nitric oxide synthase (NOS) occurring in the two cell types are responsible for the conservative or nonconservative digestion of NOS isozymes. Consistently, we demonstrate that, in the absence of Ca2+, HSP90 forms binary complexes with NOS isozymes or with calpain. When Ca2+ is present, a ternary complex containing the three proteins is produced. In this associated state, HSP90 and NOS forms are almost completely resistant to calpain digestion, probably due to a structural hindrance and a reduction in the catalytic efficiency of the protease. Thus, the recruitment of calpain in the HSP90-NOS complexes reduces the extent of the proteolysis of these two proteins. We have also observed that calpastatin competes with HSP90 for the binding of calpain in reconstructed systems. Digestion of the proteins present in the complexes can occur only when free active calpain is present in the system. This process can be visualized as a novel mechanism involving the association of NOS with HSP90 and the concomitant recruitment of active calpain in ternary complexes in which the proteolysis of both NOS isozymes and HSP90 is significantly reduced. PMID:17970747

  16. Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation

    Directory of Open Access Journals (Sweden)

    Wang Ting

    2012-08-01

    Full Text Available Abstract Background Exposure to particulate matter (PM is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. Objectives We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC barrier integrity and enhanced cardiopulmonary dysfunction. Methods Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm. Biochemical assessment of ROS generation and Ca2+ mobilization were also measured. Results PM exposure induced tight junction protein Zona occludens-1 (ZO-1 relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin. N-acetyl-cysteine (NAC, 5 mM reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2, in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. Conclusions These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.

  17. Effect of exercise training on calpain systems in lean and obese Zucker rats

    OpenAIRE

    Hsieh, Yao-Yuan; Chang, Chi-Chen; Hsu, Kung-Hao; Tsai, Fuu-Jen; Chen, Chih-Ping; Tsai, Horng-Der

    2008-01-01

    Exercise training plays a major role in the improving physiology of diabetes. Herein we aimed to investigate the influence of exercise upon the calcium-dependent calpain-isoform expressions of lean or obese Zucker rats, a model of obesity and type II diabetes (NIDDM). Five-month-old rats were divided: (1) obese sedentary (OS, n=7); (2) obese exercise (OE, n=7); (3) lean sedentary (LS, n=7); (4) lean exercise (LE, n=7). After 2-month exercise (treadmill running), the body weight (BW) and expre...

  18. Skeletal Muscle-specific Calpain and Protein Degradation%骨骼肌特异性钙蛋白酶与蛋白质降解

    Institute of Scientific and Technical Information of China (English)

    张勇; 邓科

    2011-01-01

    骨骼肌特异性钙蛋白酶calpain-3是钙蛋白酶系统的一员,与肌细胞生成和细胞凋亡密切相关,同时也被认为参与了蛋白质降解过程.本文主要从骨骼肌特异性钙蛋白酶的结构功能和生理活性,并结合近年来国际上的研究成果来分析骨骼肌特异性钙蛋白酶在骨骼肌蛋白质降解中的作用.%Calpain-3, also named as skeletal muscle-specific calpain, is a member of the calpain system. Calpain-3 has been shown to be involved in myogenesis and apoptosis, and it also plays a role in protein degradation. This article mainly reviewed the structure, function and physiological activity of calpain-3, combined with recent international research advances, to analyze the roles of calpain-3 in skeletal muscle protein degradation. [Chinese Journal of Animal Nutrition, 2011,23 ( 4 ): 542-545

  19. Polymorphisms in calpastatin and mu-calpain genes are associated with beef iron content.

    Science.gov (United States)

    Casas, E; Duan, Q; Schneider, M J; Shackelford, S D; Wheeler, T L; Cundiff, L V; Reecy, J M

    2014-04-01

    The objective of this study was to assess the association of markers in the calpastatin and mu-calpain loci with iron in beef cattle muscle. The population consisted of 259 cross-bred steers from Beefmaster, Brangus, Bonsmara, Romosinuano, Hereford and Angus sires. Total iron and heme iron concentrations were measured. Markers in the calpastatin (referred to as CAST) and mu-calpain (referred to as CAPN4751) genes were used to assess their association with iron levels. The mean and standard error for iron and heme iron content in the population was 35.6 ± 1.3 μg and 27.1 ± 1.4 μg respectively. Significant associations (P < 0.01) of markers were observed for both iron and heme iron content. For CAST, animals with the CC genotype had higher levels of iron and heme iron in longissimus dorsi muscle. For CAPN4751, individuals with the TT genotype had higher concentrations of iron and heme iron than did animals with the CC and CT genotypes. Genotypes known to be associated with tougher meat were associated with higher levels of iron concentration. PMID:24303986

  20. Activation of mitochondrial calpain and increased cardiac injury: beyond AIF release.

    Science.gov (United States)

    Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J; Chen, Qun

    2016-02-01

    Calpain 1 (CPN1) is a ubiquitous cysteine protease that exists in both cytosol and cardiac mitochondria. Mitochondrial CPN1 (mit-CPN1) is located in the intermembrane space and matrix. Activation of mit-CPN1 within the intermembrane space increases cardiac injury by releasing apoptosis-inducing factor from mitochondria during ischemia-reperfusion (IR). We asked if activation of mit-CPN1 is involved in mitochondrial injury during IR. MDL-28170 (MDL) was used to inhibit CPN1 in buffer-perfused hearts following 25-min ischemia and 30-min reperfusion. MDL treatment decreased the release of lactate dehydrogenase into coronary effluent compared with untreated hearts, indicating that inhibition of CPN1 decreases cardiac injury. MDL also prevented the cleavage of spectrin (a substrate of CPN1) in cytosol during IR, supporting that MDL treatment decreased cytosolic calpain activation. In addition, MDL markedly improved calcium retention capacity compared with untreated heart, suggesting that MDL treatment decreases mitochondrial permeability transition pore opening. In addition, we found that IR led to decreased complex I activity, whereas inhibition of mit-CPN1 using MDL protected complex I. Pyruvate dehydrogenase content was decreased following IR. However, pyruvate dehydrogenase content was preserved in MDL-treated mitochondria. Taken together, MDL treatment decreased cardiac injury during IR by inhibiting both cytosolic and mit-CPN1. Activation of mit-CPN1 increases cardiac injury during IR by sensitizing mitochondrial permeability transition pore opening and impairing mitochondrial metabolism through damage of complex I. PMID:26637561

  1. A New Insight into the Role of Calpains in Post-mortem Meat Tenderization in Domestic Animals: A review.

    Science.gov (United States)

    Lian, Ting; Wang, Linjie; Liu, Yiping

    2013-03-01

    Tenderness is the most important meat quality trait, which is determined by intracellular environment and extracellular matrix. Particularly, specific protein degradation and protein modification can disrupt the architecture and integrity of muscle cells so that improves the meat tenderness. Endogenous proteolytic systems are responsible for modifying proteinases as well as the meat tenderization. Abundant evidence has testified that calpains (CAPNs) including calpain I (CAPN1) and calpastatin (CAST) have the closest relationship with tenderness in livestock. They are involved in a wide range of physiological processes including muscle growth and differentiation, pathological conditions and post-mortem meat aging. Whereas, Calpain3 (CAPN3) has been established as an important activating enzyme specifically expressed in livestock's skeletal muscle, but its role in domestic animals meat tenderization remains controversial. In this review, we summarize the role of CAPN1, calpain II (CAPN2) and CAST in post-mortem meat tenderization, and analyse the relationship between CAPN3 and tenderness in domestic animals. Besides, the possible mechanism affecting post-mortem meat aging and improving meat tenderization, and current possible causes responsible for divergence (whether CAPN3 contributes to animal meat tenderization or not) are inferred. Only the possible mechanism of CAPN3 in meat tenderization has been confirmed, while its exact role still needs to be studied further. PMID:25049808

  2. Searching Inhibitors of Adenosine Kinase by Simulation Methods

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-Xin; ZHANG Xing-Long; DONG Xi-Cheng; CHEN Min-Bo

    2006-01-01

    Searching new inhibitors of adenosine kinase (AK) is still drawing attention of experimental scientists. A better and solid model is here proposed by means of simulation methods from different ways, the direct analysis of receptor itself, the conventional 3D-QSAR methods and the integration of docking method and the conventional QSAR analysis.

  3. Arabidopsis CDS blastp result: AK102264 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102264 J033088M02 At4g22670.1 tetratricopeptide repeat (TPR)-containing protein similar to Hsc ... 70-interacting protein (Hip ) from {Homo sapiens} SP|P50502, {Rattus norvegicus ...

  4. Arabidopsis CDS blastp result: AK119708 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119708 002-157-E08 At1g28330.1 dormancy-associated protein, putative (DRM1) identical to dormancy...-associated protein [Arabidopsis thaliana] GI:2995990; similar to dormancy-associated protei

  5. Arabidopsis CDS blastp result: AK060981 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060981 006-202-H08 At1g28330.1 dormancy-associated protein, putative (DRM1) identical to dormancy...-associated protein [Arabidopsis thaliana] GI:2995990; similar to dormancy-associated protei

  6. Arabidopsis CDS blastp result: AK111736 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111736 J023047L09 At1g68370.1 gravity -responsive protein / altered response to gravity ... protein ... (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  7. Arabidopsis CDS blastp result: AK065579 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065579 J013031C20 At3g05480.1 cell cycle checkpoint control protein family contains Pfam profi ... ein N-myristoyltransferase signature 2; similar to radio -resistance/chemo-resistance/cell cycle checkpoint ...

  8. Arabidopsis CDS blastp result: AK105135 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105135 001-102-A05 At2g27170.1 structural maintenance of chromosomes (SMC) family protein similar to basem...ent membrane-associated chondroitin proteoglycan Bamacan [Rattus norvegicus] GI:178

  9. Arabidopsis CDS blastp result: AK070093 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070093 J023041M10 At2g39290.1 phosphatidylglycerolphosphate synthase (PGS1) identical to phosphati...dylglycerolphosphate synthase GI:13365519 from [Arabidopsis thaliana] 7e-78 ...

  10. Arabidopsis CDS blastp result: AK060009 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060009 006-302-D03 At2g39290.1 phosphatidylglycerolphosphate synthase (PGS1) identical to phosphati...dylglycerolphosphate synthase GI:13365519 from [Arabidopsis thaliana] 8e-71 ...

  11. Arabidopsis CDS blastp result: AK064999 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064999 J013001E01 At3g20250.1 pumilio /Puf RNA-binding domain-containing protein contains Pfam ... profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  12. Arabidopsis CDS blastp result: AK067341 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067341 J013105N21 At1g72320.1 pumilio /Puf RNA-binding domain-containing protein contains Pfam ... profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  13. Arabidopsis CDS blastp result: AK070870 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070870 J023075A04 At3g20250.1 pumilio /Puf RNA-binding domain-containing protein contains Pfam ... profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  14. Arabidopsis CDS blastp result: AK121028 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121028 J023050G17 At1g78160.1 pumilio /Puf RNA-binding domain-containing protein contains Pfam ... profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  15. Arabidopsis CDS blastp result: AK121539 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121539 J033031I02 At3g20250.1 pumilio /Puf RNA-binding domain-containing protein contains Pfam ... profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  16. Arabidopsis CDS blastp result: AK240887 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240887 J065029G04 At5g01650.1 68418.m00081 macrophage migration ... inhibitory factor family prote ... protein contains pfam profile: PF001187 Macrophage migration ... inhibitory factor 3e-49 ...

  17. Arabidopsis CDS blastp result: AK121033 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121033 J023050K24 At5g01650.1 macrophage migration ... inhibitory factor family protein / MIF fami ... protein contains pfam profile: PF001187 Macrophage migration ... inhibitory factor 1e-44 ...

  18. Arabidopsis CDS blastp result: AK062047 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062047 001-044-A11 At5g57170.1 macrophage migration ... inhibitory factor family protein / MIF fam ... protein contains Pfam profile: PF01187 Macrophage migration ... inhibitory factor(MIF) 3e-34 ...

  19. PIR search result: AK121428 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121428 J023136H14 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 4 ...

  20. PIR search result: AK105449 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105449 001-125-B12 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gl ... ycosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 1 ...

  1. PIR search result: AK121014 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121014 J023048A03 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 4 ...

  2. PIR search result: AK243062 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243062 J100014O03 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 1 ...

  3. PIR search result: AK119824 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119824 002-177-D07 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gl ... ycosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 1 ...

  4. PIR search result: AK066051 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066051 J013051B02 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 6 ...

  5. PIR search result: AK063966 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK063966 001-124-A04 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gl ... ycosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 2 ...

  6. PIR search result: AK121588 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK121588 J033037N10 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 2 ...

  7. PIR search result: AK102309 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102309 J033090B18 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 3 ...

  8. PIR search result: AK101307 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101307 J033033M11 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gly ... cosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 1 ...

  9. PIR search result: AK110088 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK110088 002-160-G07 P1;F97255 fusion of alpha-glucosidase (family ... 31 glycosyl hydrolase) and gl ... ycosidase (TreA/MalS family ) CAC2891 [imported] - Clostridium acetobutylicum 2 ...

  10. Arabidopsis CDS blastp result: AK104609 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104609 006-309-C02 At3g62060.1 pectinacetylesterase family protein similar to pectin...acetylesterase precursor GI:1431629 from [Vigna radiata]; contains Pfam profile: PF03283 pectinacetylesterase 1e-110 ...

  11. Arabidopsis CDS blastp result: AK064109 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064109 002-101-G02 At3g09410.3 pectinacetylesterase family protein similar to pectin...acetylesterase precursor GB:CAA67728 [Vigna radiata]; contains Pfam profile: PF03283 pectinacetylesterase 1e-126 ...

  12. Arabidopsis CDS blastp result: AK058419 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK058419 001-015-D06 At4g16280.3 flowering time ... control protein / FCA gamma (FCA) identical to S ... P|O04425 Flowering time ... control protein FCA {Arabidopsis thaliana}; four a ...

  13. Arabidopsis CDS blastp result: AK073225 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073225 J033023C04 At4g16280.3 flowering time ... control protein / FCA gamma (FCA) identical to SP ... |O04425 Flowering time ... control protein FCA {Arabidopsis thaliana}; four a ...

  14. Arabidopsis CDS blastp result: AK102695 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102695 J033103F21 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 0.0 ...

  15. Arabidopsis CDS blastp result: AK102134 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102134 J033085F12 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 0.0 ...

  16. Arabidopsis CDS blastp result: AK066835 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066835 J013087I16 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 1e-171 ...

  17. Arabidopsis CDS blastp result: AK065259 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065259 J013002J18 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 0.0 ...

  18. Arabidopsis CDS blastp result: AK100523 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100523 J023100P04 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 0.0 ...

  19. Arabidopsis CDS blastp result: AK101105 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101105 J033025D11 At2g39090.1 tetratricopeptide repeat (TPR)-containing protein low similarity to prediabe...tic NOD sera-reactive autoantigen [Mus musculus] GI:6670773, anaphase-promoting com

  20. Arabidopsis CDS blastp result: AK243084 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243084 J100020N17 At4g10100.1 68417.m01652 molybdenum cofactor synthesis ... family protein simila ... r to Molybdenum cofactor synthesis ... protein 2 small subunit (Molybdopterin- synthase s ...

  1. Arabidopsis CDS blastp result: AK243084 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243084 J100020N17 At4g10100.2 68417.m01653 molybdenum cofactor synthesis ... family protein simila ... r to Molybdenum cofactor synthesis ... protein 2 small subunit (Molybdopterin- synthase s ...

  2. Arabidopsis CDS blastp result: AK066419 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066419 J013066N17 At5g67590.1 NADH-ubiquinone oxidoreductase-related contains weak similarity ... 25711) [Neurospora crassa]; contains Pfam PF04800: ETC ... complex I subunit conserved region 1e-53 ...

  3. Arabidopsis CDS blastp result: AK288002 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288002 J075110B01 At1g68510.1 68414.m07826 LOB domain protein 42 ... / lateral organ boundaries do ... main protein 42 ... (LBD42 ) identical to LOB DOMAIN 42 ... [Arabidopsis th ...

  4. Arabidopsis CDS blastp result: AK243548 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243548 J100079E11 At3g05500.1 68416.m00602 rubber ... elongation factor (REF) family protein conta ... ins Pfam profile: PF05755 rubber ... elongation factor protein (REF) 2e-47 ...

  5. Arabidopsis CDS blastp result: AK243548 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243548 J100079E11 At1g67360.2 68414.m07668 rubber ... elongation factor (REF) family protein conta ... ins Pfam profile: PF05755 rubber ... elongation factor protein (REF) 3e-19 ...

  6. Arabidopsis CDS blastp result: AK243548 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243548 J100079E11 At1g67360.1 68414.m07667 rubber ... elongation factor (REF) family protein conta ... ins Pfam profile: PF05755 rubber ... elongation factor protein (REF) 3e-19 ...

  7. PIR search result: AK109905 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109905 002-149-G04 F1;S26284 retrovirus-related reverse transcriptase homolog (clone Da4) - tr ... ee fern (Dicksonia antarctica ) retrotransposon copia-like Ty1 (fragment) 3e-11 ...

  8. PIR search result: AK111829 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111829 J023073M14 F1;S26284 retrovirus-related reverse transcriptase homolog (clone Da4) - tre ... e fern (Dicksonia antarctica ) retrotransposon copia-like Ty1 (fragment) 2e-12 ...

  9. PIR search result: AK100661 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100661 J023111N02 F1;S26284 retrovirus-related reverse transcriptase homolog (clone Da4) - tre ... e fern (Dicksonia antarctica ) retrotransposon copia-like Ty1 (fragment) 3e-12 ...

  10. PIR search result: AK111724 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111724 J023029P03 F1;S26284 retrovirus-related reverse transcriptase homolog (clone Da4) - tre ... e fern (Dicksonia antarctica ) retrotransposon copia-like Ty1 (fragment) 8e-12 ...

  11. PIR search result: AK119307 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119307 001-130-F11 F1;S26284 retrovirus-related reverse transcriptase homolog (clone Da4) - tr ... ee fern (Dicksonia antarctica ) retrotransposon copia-like Ty1 (fragment) 6e-11 ...

  12. Arabidopsis CDS blastp result: AK111785 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111785 J023089N11 At5g62310.1 incomplete root hair ... elongation (IRE) / protein kinase, putative ... nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  13. Arabidopsis CDS blastp result: AK243050 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243050 J100011E04 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  14. Arabidopsis CDS blastp result: AK242758 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242758 J090051H03 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  15. Arabidopsis CDS blastp result: AK242717 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242717 J090043H19 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  16. Arabidopsis CDS blastp result: AK288095 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288095 J075191E21 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  17. Arabidopsis CDS blastp result: AK242638 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242638 J090023J02 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  18. Arabidopsis CDS blastp result: AK242651 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242651 J090026B08 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  19. Arabidopsis CDS blastp result: AK287631 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287631 J065073J24 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  20. Arabidopsis CDS blastp result: AK288923 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288923 J090081P06 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  1. Arabidopsis CDS blastp result: AK242271 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242271 J075187A19 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  2. Arabidopsis CDS blastp result: AK242681 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242681 J090032N04 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  3. Arabidopsis CDS blastp result: AK243656 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243656 J100088L22 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  4. Arabidopsis CDS blastp result: AK241519 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241519 J065170E12 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  5. Arabidopsis CDS blastp result: AK240655 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240655 J023135E11 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  6. Arabidopsis CDS blastp result: AK242733 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242733 J090047O22 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  7. Arabidopsis CDS blastp result: AK242859 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242859 J090073L24 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  8. Arabidopsis CDS blastp result: AK243187 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243187 J100039E11 At5g62310.1 68418.m07822 incomplete root hair ... elongation (IRE) / protein kin ... putative nearly identical to IRE (incomplete root hair ... elongation) [Arabidopsis thaliana] gi|6729346|dbj| ...

  9. Arabidopsis CDS blastp result: AK242550 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242550 J080319D10 At2g35630.1 68415.m04369 microtubule organization 1 protein (MO...R1) identical to microtubule organization 1 protein GI:14317953 from [Arabidopsis thaliana] 5e-44 ...

  10. Arabidopsis CDS blastp result: AK101748 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101748 J033061P17 At5g01260.2 glycoside hydrolase starch-binding domain-containing protein low ... extrin glucanotransferase precursor (EC 2.4.1.19) (Cyclodextrin -glycosyltransferase) (CGTase) {Bacillus stearother ...

  11. Arabidopsis CDS blastp result: AK107570 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107570 002-130-D02 At5g01260.2 glycoside hydrolase starch-binding domain-containing protein lo ... extrin glucanotransferase precursor (EC 2.4.1.19) (Cyclodextrin -glycosyltransferase) (CGTase) {Bacillus stearother ...

  12. Arabidopsis CDS blastp result: AK103177 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103177 J033121H17 At4g35785.2 transformer serine/arginine-rich ribonucleoprotein,... putative similar to transformer-SR ribonucleoprotein [Nicotiana tabacum] gi|1781299|emb|CAA70700 1e-25 ...

  13. Arabidopsis CDS blastp result: AK073850 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073850 J033073F11 At4g35785.2 transformer serine/arginine-rich ribonucleoprotein,... putative similar to transformer-SR ribonucleoprotein [Nicotiana tabacum] gi|1781299|emb|CAA70700 4e-26 ...

  14. Arabidopsis CDS blastp result: AK120103 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK120103 J013022N16 At5g57170.1 macrophage migration inhibitory factor family prote...in / MIF family protein contains Pfam profile: PF01187 Macrophage migration inhibitory factor(MIF) 3e-34 ...

  15. Arabidopsis CDS blastp result: AK073290 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073290 J033025L21 At5g17230.1 phytoene synthase (PSY) / geranylgeranyl-diphosphate geranylgeranyl... transferase identical to GB:L25812; synonymous with geranylgeranyl-diphosphate geranylgeranyl transferase 1e-142 ...

  16. Arabidopsis CDS blastp result: AK059535 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059535 001-029-E01 At5g17230.1 phytoene synthase (PSY) / geranylgeranyl-diphosphate geranylgeranyl... transferase identical to GB:L25812; synonymous with geranylgeranyl-diphosphate geranylgeranyl transferase 3e-56 ...

  17. Arabidopsis CDS blastp result: AK067762 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067762 J013116E15 At5g17230.1 phytoene synthase (PSY) / geranylgeranyl-diphosphate geranylgeranyl... transferase identical to GB:L25812; synonymous with geranylgeranyl-diphosphate geranylgeranyl transferase 2e-86 ...

  18. Arabidopsis CDS blastp result: AK108154 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK108154 002-139-G05 At5g17230.1 phytoene synthase (PSY) / geranylgeranyl-diphosphate geranylgeranyl... transferase identical to GB:L25812; synonymous with geranylgeranyl-diphosphate geranylgeranyl transferase 1e-134 ...

  19. Arabidopsis CDS blastp result: AK063967 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK063967 001-124-A11 At5g17230.1 phytoene synthase (PSY) / geranylgeranyl-diphosphate geranylgeranyl... transferase identical to GB:L25812; synonymous with geranylgeranyl-diphosphate geranylgeranyl transferase 1e-128 ...

  20. Arabidopsis CDS blastp result: AK070716 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070716 J023057D05 At5g17230.1 phytoene synthase (PSY) / geranylgeranyl-diphosphate geranylgeranyl... transferase identical to GB:L25812; synonymous with geranylgeranyl-diphosphate geranylgeranyl transferase 1e-156 ...

  1. Arabidopsis CDS blastp result: AK101368 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101368 J033035L13 At5g24270.1 calcineurin B-like protein, putative / calcium sensor ... homolog (S ... OS3) identical to calcium sensor ... homolog [Arabidopsis thaliana] GI:3309575; similar ...

  2. Arabidopsis CDS blastp result: AK111570 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111570 J013071C24 At5g24270.1 calcineurin B-like protein, putative / calcium sensor ... homolog (S ... OS3) identical to calcium sensor ... homolog [Arabidopsis thaliana] GI:3309575; similar ...

  3. Arabidopsis CDS blastp result: AK243065 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243065 J100015N03 At5g24270.1 68418.m02855 calcineurin B-like protein, putative / calcium sensor ... or homolog (SOS3) identical to calcium sensor ... homolog [Arabidopsis thaliana] GI:3309575; similar ...

  4. Arabidopsis CDS blastp result: AK069624 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069624 J023025F15 At1g15500.1 chloroplast ADP, ATP carrier protein, putative / ADP, ATP transl ... bidopsis thaliana}; contains Pfam profile PF03219: TLC ... ATP/ADP transporter 0.0 ...

  5. Arabidopsis CDS blastp result: AK103738 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103738 J033138K07 At1g15500.1 chloroplast ADP, ATP carrier protein, putative / ADP, ATP transl ... bidopsis thaliana}; contains Pfam profile PF03219: TLC ... ATP/ADP transporter 1e-168 ...

  6. Arabidopsis CDS blastp result: AK102610 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102610 J033099C15 At1g15500.1 chloroplast ADP, ATP carrier protein, putative / ADP, ATP transl ... bidopsis thaliana}; contains Pfam profile PF03219: TLC ... ATP/ADP transporter 0.0 ...

  7. Arabidopsis CDS blastp result: AK070528 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070528 J023060D13 At3g10920.1 superoxide dismutase [Mn], mitochondrial (SODA) / manganese ... supe ... roxide dismutase (MSD1) identical to manganese ... superoxide dismutase [Arabidopsis thaliana] gi|327 ...

  8. Arabidopsis CDS blastp result: AK119904 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119904 002-182-A05 At3g10920.1 superoxide dismutase [Mn], mitochondrial (SODA) / manganese ... sup ... eroxide dismutase (MSD1) identical to manganese ... superoxide dismutase [Arabidopsis thaliana] gi|327 ...

  9. Arabidopsis CDS blastp result: AK104030 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104030 001-020-C01 At3g10920.1 superoxide dismutase [Mn], mitochondrial (SODA) / manganese ... sup ... eroxide dismutase (MSD1) identical to manganese ... superoxide dismutase [Arabidopsis thaliana] gi|327 ...

  10. Arabidopsis CDS blastp result: AK104160 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104160 006-211-E09 At3g10920.1 superoxide dismutase [Mn], mitochondrial (SODA) / manganese ... sup ... eroxide dismutase (MSD1) identical to manganese ... superoxide dismutase [Arabidopsis thaliana] gi|327 ...

  11. Arabidopsis CDS blastp result: AK060067 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060067 006-305-H07 At3g44620.1 low molecular ... weight phosphotyrosine protein phosphatase family ... protein contains Pfam profile: PF01451 low molecular ... weight phosphotyrosine protein phosphatase 7e-69 ...

  12. Arabidopsis CDS blastp result: AK067011 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067011 J013093K20 At3g06170.1 TMS ... membrane family protein / tumour differentially expressed (T ... DE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  13. Arabidopsis CDS blastp result: AK119191 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119191 001-039-H03 At1g16180.1 TMS ... membrane family protein / tumour differentially expressed ( ... TDE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  14. Arabidopsis CDS blastp result: AK068367 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK068367 J013147C17 At1g16180.1 TMS ... membrane family protein / tumour differentially expressed (T ... DE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  15. Arabidopsis CDS blastp result: AK106174 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK106174 001-208-C06 At1g16180.1 TMS ... membrane family protein / tumour differentially expressed ( ... TDE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  16. Arabidopsis CDS blastp result: AK063591 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK063591 001-118-A12 At2g33205.1 TMS ... membrane family protein / tumour differentially expressed ( ... TDE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  17. Arabidopsis CDS blastp result: AK104731 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104731 001-038-C07 At1g16180.1 TMS ... membrane family protein / tumour differentially expressed ( ... TDE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  18. Arabidopsis CDS blastp result: AK069734 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069734 J023033E12 At4g13345.1 TMS ... membrane family protein / tumour differentially expressed (T ... DE) family protein contains Pfam domain, PF03348: TMS ... membrane protein/tumour differentially expressed p ...

  19. Arabidopsis CDS blastp result: AK103225 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103225 J033123A19 At2g39710.1 aspartyl protease family protein contains profile Pfam PF00026: ... ins Prosite PS00141: Eukaryotic and viral aspartyl proteases ... active site.; 1e-107 ...

  20. Arabidopsis CDS blastp result: AK101206 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101206 J033030P16 At2g39710.1 aspartyl protease family protein contains profile Pfam PF00026: ... ins Prosite PS00141: Eukaryotic and viral aspartyl proteases ... active site.; 1e-107 ...

  1. Arabidopsis CDS blastp result: AK067853 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067853 J013122O17 At4g16440.1 iron ... hydrogenase family protein contains Pfam profiles: PF02906 ... rogenase large subunit, C-terminal domain, PF02256 Iron ... hydrogenase small subunit 1e-153 ...

  2. Arabidopsis CDS blastp result: AK099942 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099942 J013121N13 At3g12100.1 cation efflux family protein / metal tolerance protein, putative ... member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  3. Arabidopsis CDS blastp result: AK110750 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK110750 002-170-G06 At3g58060.1 cation efflux family protein / metal tolerance protein, putativ ... e (MTPc3) member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  4. Arabidopsis CDS blastp result: AK065961 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065961 J013043M15 At3g58060.1 cation efflux family protein / metal tolerance protein, putative ... (MTPc3) member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  5. Arabidopsis CDS blastp result: AK107653 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107653 002-131-G02 At3g58060.1 cation efflux family protein / metal tolerance protein, putativ ... e (MTPc3) member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  6. Arabidopsis CDS blastp result: AK287891 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287891 J065209I11 At3g12100.1 68416.m01506 cation efflux family protein / metal tolerance prot ... ein, putative member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  7. Arabidopsis CDS blastp result: AK099439 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099439 J013020D21 At3g12100.1 cation efflux family protein / metal tolerance protein, putative ... member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  8. Arabidopsis CDS blastp result: AK070223 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK070223 J023041B15 At3g58060.1 cation efflux family protein / metal tolerance protein, putative ... (MTPc3) member of the cation diffusion ... facilitator (CDF) family, or cation efflux (CE) fa ...

  9. Arabidopsis CDS blastp result: AK287459 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287459 J043019O07 At4g37000.1 68417.m05242 accelerated cell death ... 2 (ACD2) identical to accele ... rated cell death ... 2 (ACD2) GI:12484129 from [Arabidopsis thaliana] 4 ...

  10. Arabidopsis CDS blastp result: AK288034 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288034 J075140H07 At4g37000.1 68417.m05242 accelerated cell death ... 2 (ACD2) identical to accele ... rated cell death ... 2 (ACD2) GI:12484129 from [Arabidopsis thaliana] 5 ...

  11. Arabidopsis CDS blastp result: AK111576 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111576 J013075J23 At1g01510.1 C-terminal binding protein (ANGUSTIFOLIA) nearly id...entical to C-terminal binding protein ANGUSTIFOLIA [Arabidopsis thaliana] GI:15408535; contains Pfam profile

  12. Arabidopsis CDS blastp result: AK120838 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK120838 J023022B11 At1g01510.1 C-terminal binding protein (ANGUSTIFOLIA) nearly id...entical to C-terminal binding protein ANGUSTIFOLIA [Arabidopsis thaliana] GI:15408535; contains Pfam profile

  13. Arabidopsis CDS blastp result: AK111921 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111921 001-013-A10 At1g01510.1 C-terminal binding protein (ANGUSTIFOLIA) nearly i...dentical to C-terminal binding protein ANGUSTIFOLIA [Arabidopsis thaliana] GI:15408535; contains Pfam profil

  14. AkP from mushroom Termitomyces clypeatus is a proteoglycan specific protease with apoptotic effect on HepG2.

    Science.gov (United States)

    Majumder, Rajib; Banik, Samudra Prosad; Khowala, Suman

    2016-10-01

    Termitomyces clypeatus is an edible mushroom, prized for its therapeutic values and as producer of industrially important enzymes. However, the biomedical efficacies of anticancer proteases have not been reported yet. The present study aimed to purify and characterize a serine protease (AkP) from T. clypeatus for investigating cytotoxic potency on HepG2, Hep3B, and compared the effect on normal hepatic L-02 cells. Purification and biochemical characterization of AkP were evaluated by three stage chromatography, 1D/2D-SDS-PAGE, 1D zymography, far-UV CD spectral analysis, N-terminal sequencing, MALDI-TOF/MS-MS analysis and enzyme kinetics studies. AkP could cleave the growth promoting cell surface proteoglycans of HepG2, corroborated by RP-HPLC analysis. AkP (IC50: 75±1.18nM) mediated anti-proliferative activity solely on HepG2 cells through the induction of apoptosis. Augmentation of apoptosis was attributed to up-regulation of p53 and Bax protein expression succeeded by caspase-3 activation. Serine protease inhibitor phenyl methane sulfonyl fluoride (PMSF) inhibited both its proteolytic activity and cytotoxicity on HepG2. These findings demonstrate that AkP could be an effective biomolecule for killing of cancer cells by p53 restoration and surface proteoglycans cleavage. PMID:27180294

  15. Investigation on CAST, CAPN1 and CAPN3 porcine gene polymorphisms and expression in relation to post-mortem calpain activity in muscle and meat quality.

    Science.gov (United States)

    Gandolfi, G; Pomponio, L; Ertbjerg, P; Karlsson, A H; Nanni Costa, L; Lametsch, R; Russo, V; Davoli, R

    2011-08-01

    This study aimed to detect variability in CAST, CAPN1 and CAPN3 porcine genes and to investigate the effect of CAST and CAPN1 polymorphisms on the activity of native and autolyzed μ-calpain and m-calpain, measured from 1 to 72 h post-mortem in Longissimus dorsi (LD) muscle of 30 pigs. Effects of polymorphisms on meat quality parameter such as pH, color and drip loss were also evaluated. Samples carrying CAST EU137105:g.76,872AA genotype showed higher autolyzed μ-calpain activity 24 and 72 h post-mortem, as well as lower drip loss values. Expression of CAST, CAPN1 and CAPN3 was assessed in LD muscles divergent for shear force. Higher CAST and CAPN3 expression was found in LD with high shear force (Ptenderization. In conclusion, CAST gene affected post-mortem activation time of calpain and drip loss. PMID:21450414

  16. Identification of different domains of calpain and calpastatin from chicken blood and their role in post-mortem aging of meat during holding at refrigeration temperatures.

    Science.gov (United States)

    Biswas, A K; Tandon, S; Beura, C K

    2016-06-01

    The aim of this study was to develop a simple, specific and rapid analytical method for accurate identification of calpain and calpastatin from chicken blood and muscle samples. The method is based on liquid-liquid extraction technique followed by casein Zymography detection. The target compounds were extracted from blood and meat samples by tris buffer, and purified and separated on anion exchange chromatography. It has been observed that buffer (pH 6.7) containing 50 mM tris-base appears to be excellent extractant as activity of analytes was maximum for all samples. The concentrations of μ-, m-calpain and calpastatin detected in the extracts of blood, breast and thigh samples were 0.28-0.55, 1.91-2.05 and 1.38-1.52 Unit/g, respectively. For robustness, the analytical method was applied to determine the activity of calpains (μ and m) in eighty postmortem muscle samples. It has been observed that μ-calpain activity in breast and thigh muscles declined very rapidly at 48 h and 24 h, respectively while activity of m-calpain remained stable. Shear force values were also declined with the increase of post-mortem aging showing the presence of ample tenderness of breast and thigh muscles. Finally, it is concluded that the method standardized for the detection of calpain and calpastatin has the potential to be applied to identify post-mortem aging of chicken meat samples. PMID:26830594

  17. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ronghua Wu

    2015-11-01

    Full Text Available Calpain 3 (CAPN3, also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.

  18. Effect of nutrient restriction and re-feeding on calpain family genes in skeletal muscle of channel catfish (Ictalurus punctatus.

    Directory of Open Access Journals (Sweden)

    Elena Preziosa

    Full Text Available BACKGROUND: Calpains, a superfamily of intracellular calcium-dependent cysteine proteases, are involved in the cytoskeletal remodeling and wasting of skeletal muscle. Calpains are generated as inactive proenzymes which are activated by N-terminal autolysis induced by calcium-ions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we characterized the full-length cDNA sequences of three calpain genes, clpn1, clpn2, and clpn3 in channel catfish, and assessed the effect of nutrient restriction and subsequent re-feeding on the expression of these genes in skeletal muscle. The clpn1 cDNA sequence encodes a protein of 704 amino acids, Clpn2 of 696 amino acids, and Clpn3 of 741 amino acids. Phylogenetic analysis of deduced amino acid sequences indicate that catfish Clpn1 and Clpn2 share a sequence similarity of 61%; catfish Clpn1 and Clpn3 of 48%, and Clpn2 and Clpn3 of only 45%. The domain structure architectures of all three calpain genes in channel catfish are similar to those of other vertebrates, further supported by strong bootstrap values during phylogenetic analyses. Starvation of channel catfish (average weight, 15-20 g for 35 days influenced the expression of clpn1 (2.3-fold decrease, P<0.05, clpn2 (1.3-fold increase, P<0.05, and clpn3 (13.0-fold decrease, P<0.05, whereas the subsequent refeeding did not change the expression of these genes as measured by quantitative real-time PCR analysis. Calpain catalytic activity in channel catfish skeletal muscle showed significant differences only during the starvation period, with a 1.2- and 1.4- fold increase (P<0.01 after 17 and 35 days of starvation, respectively. CONCLUSION/SIGNIFICANCE: We have assessed that fasting and refeeding may provide a suitable experimental model to provide us insight into the role of calpains during fish muscle atrophy and how they respond to changes in nutrient supply.

  19. The calpain, caspase 12, caspase 3 cascade leading to apoptosis is altered in F508del-CFTR expressing cells.

    Directory of Open Access Journals (Sweden)

    Mathieu Kerbiriou

    Full Text Available In cystic fibrosis (CF, the most frequent mutant variant of the cystic fibrosis transmembrane conductance regulator (CFTR, F508del-CFTR protein, is misfolded and retained in the endoplasmic reticulum (ER. We previously showed that the unfolded protein response (UPR may be triggered in CF. Since prolonged UPR activation leads to apoptosis via the calcium-calpain-caspase-12-caspase-3 cascade and because apoptosis is altered in CF, our aim was to compare the ER stress-induced apoptosis pathway between wild type (Wt and F508del-CFTR expressing cells. Here we show that the calcium-calpain-caspase-12-caspase-3 cascade is altered in F508del-CFTR expressing cells. We propose that this alteration is involved in the altered apoptosis triggering observed in CF.

  20. Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation.

    Science.gov (United States)

    Xu, Guo-Jun; Gan, Tian-Yi; Tang, Bao-Peng; Chen, Zu-Heng; Mahemuti, Ailiman; Jiang, Tao; Song, Jian-Guo; Guo, Xia; Li, Yao-Dong; Zhou, Xian-Hui; Zhang, Yu; Li, Jin-Xin

    2013-11-01

    The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCCa1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (Pcontrol group, the mRNA and protein expression levels of LVDCCa1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (Patrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF. PMID:24043247

  1. Modulation of Intracellular Calcium Levels by Calcium Lactate Affects Colon Cancer Cell Motility through Calcium-Dependent Calpain

    OpenAIRE

    Pasupathi Sundaramoorthy; Jae Jun Sim; Yeong-Su Jang; Siddhartha Kumar Mishra; Keun-Yeong Jeong; Poonam Mander; Oh Byung Chul; Won-Sik Shim; Seung Hyun Oh; Ky-Youb Nam; Hwan Mook Kim

    2015-01-01

    Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstrea...

  2. Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1, and enhances skeletal muscle force in aging sedentary mice.

    Science.gov (United States)

    Zhang, Tan; Pereyra, Andrea S; Wang, Zhong-Min; Birbrair, Alexander; Reisz, Julie A; Files, Daniel Clark; Purcell, Lina; Feng, Xin; Messi, Maria L; Feng, Hanzhong; Chalovich, Joseph; Jin, Jian-Ping; Furdui, Cristina; Delbono, Osvaldo

    2016-06-01

    Loss of strength in human and animal models of aging can be partially attributed to a well-recognized decrease in muscle mass; however, starting at middle-age, the normalized force (force/muscle cross-sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca(2+) channel α1 subunit (Cav1.1) with aging leads to excitation-contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function. We recently reported that in addition to its classical cytoplasmic location, fast skeletal muscle troponin T3 (TnT3) is fragmented in aging mice, and both full-length TnT3 (FL-TnT3) and its carboxyl-terminal (CT-TnT3) fragment shuttle to the nucleus. Here, we demonstrate that it regulates transcription of Cacna1s, the gene encoding Cav1.1. Knocking down TnT3 in vivo downregulated Cav1.1. TnT3 downregulation or overexpression decreased or increased, respectively, Cacna1s promoter activity, and the effect was ablated by truncating the TnT3 nuclear localization sequence. Further, we mapped the Cacna1s promoter region and established the consensus sequence for TnT3 binding to Cacna1s promoter. Systemic administration of BDA-410, a specific calpain inhibitor, prevented TnT3 fragmentation, and Cacna1s and Cav1.1 downregulation and improved muscle force generation in sedentary old mice. PMID:26892246

  3. Protein kinase inhibitors in plants of the myrtaceae, proteaceae, and leguminosae.

    Science.gov (United States)

    Larkin, M; Brazier, J; Ternai, B; Polya, G M

    1993-12-01

    Methanolic extracts of leaves, flowers, stems, bark, and other parts of representative plants of the Myrtaceae, specifically of the EUCALYPTUS, MELALEUCA, THRYPTOMENA, CALLISTOMEN, ACMENA, AND ANGOPHORA genera, variously contain high levels of inhibitors of plant Ca (2+)-dependent protein kinase (CDPK) and of Ca (2+)-calmodulin-dependent myosin light chain kinase (MLCK). In terms of the protein kinase inhibition unit (PKIU), defined as the amount in the standard protein kinase assays causing 50% inhibition of protein kinase activity, these inhibitor levels ranged from the non-detectable to 179,000 PKIU (gram fresh weight) (-1) [(g FW) (-1)] and there was no consistent pattern of inhibitor distribution. A variety of other plants tested had low or non-detectable levels of CDPK and MLCK inhibitors. Plants of the EUCALYPTUS, MELALEUCA, ANGOPHORA, and GREVILLEA genera contained inhibitors of the catalytic subunit of the cyclic AMP-dependent protein kinase (cAK), inhibitor levels ranging from 20,000 to 9,600,000 PKIU (g FW) (-1). In general, cAK inhibitor levels found in the Myrtaceae were mostly much higher than levels of CDPK and MLCK inhibitors and reversed phase HPLC of such plant extracts revealed a multiplicity of components associated with cAK inhibitory activity. These IN VITRO screening procedures enable rapid detection and quantitation of levels of bioactive plant defence compounds with medicinal potential. PMID:17230363

  4. Arabidopsis CDS blastp result: AK240696 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240696 J043010A04 At5g20490.1 68418.m02435 myosin, putative similar to myosin (GI:433663) [Ara ... idopsis thaliana]; myosin-like protein my5, common sunflower , PIR:T14279 0.0 ...

  5. Arabidopsis CDS blastp result: AK062624 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK062624 001-105-B12 At1g34780.1 protein disulfide isomerase-related contains weak similarity to ... protein disulfide isomerase A4 precursor (Protein ERp -72, ERp 72) [Mus musculus] 2e-33 ...

  6. Arabidopsis CDS blastp result: AK243155 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243155 J100033B12 At1g34780.1 68414.m04329 protein disulfide isomerase-related contains weak s ... protein disulfide isomerase A4 precursor (Protein ERp -72, ERp 72) [Mus musculus] 2e-24 ...

  7. Arabidopsis CDS blastp result: AK066771 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066771 J013083K07 At1g01170.1 ozone-responsive stress-related protein, putative s...imilar to stress-related ozone-induced protein AtOZI1 (GI:790583) [Arabidopsis thaliana]; contains 1 predicted transmembrane domain; 2e-29 ...

  8. Arabidopsis CDS blastp result: AK059353 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059353 001-026-D01 At1g01170.1 ozone-responsive stress-related protein, putative ...similar to stress-related ozone-induced protein AtOZI1 (GI:790583) [Arabidopsis thaliana]; contains 1 predicted transmembrane domain; 2e-29 ...

  9. Arabidopsis CDS blastp result: AK059160 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059160 001-023-D05 At1g01170.1 ozone-responsive stress-related protein, putative ...similar to stress-related ozone-induced protein AtOZI1 (GI:790583) [Arabidopsis thaliana]; contains 1 predicted transmembrane domain; 3e-28 ...

  10. Arabidopsis CDS blastp result: AK104744 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104744 001-038-E04 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-15 ...

  11. Arabidopsis CDS blastp result: AK104590 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104590 006-307-H10 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 3e-15 ...

  12. Arabidopsis CDS blastp result: AK060980 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060980 006-202-G12 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-15 ...

  13. Arabidopsis CDS blastp result: AK104391 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104391 006-201-H09 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-15 ...

  14. Arabidopsis CDS blastp result: AK104244 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK104244 006-308-D04 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-15 ...

  15. Arabidopsis CDS blastp result: AK060136 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060136 006-309-D12 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-15 ...

  16. Arabidopsis CDS blastp result: AK106100 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK106100 001-207-C05 At1g56220.3 dormancy/auxin associated family protein similar t...in (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-15 ...

  17. Arabidopsis CDS blastp result: AK064815 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064815 J013000E10 At1g56220.3 dormancy/auxin associated family protein similar to...n (GI:927034) [Fragaria x ananassa]; similar to dormancy-associated protein (GI:2605887) [Pisum sativum] 1e-17 ...

  18. Arabidopsis CDS blastp result: AK242849 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242849 J090072M15 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  19. Arabidopsis CDS blastp result: AK288959 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288959 J090084E19 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  20. Arabidopsis CDS blastp result: AK243008 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243008 J090097H12 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  1. Arabidopsis CDS blastp result: AK288072 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288072 J075161I05 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  2. Arabidopsis CDS blastp result: AK243178 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243178 J100036P15 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  3. Arabidopsis CDS blastp result: AK243505 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243505 J100074N19 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  4. Arabidopsis CDS blastp result: AK287577 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287577 J065037N08 At1g68370.1 68414.m07809 gravity -responsive protein / altered response to gravity ... ty protein (ARG1) identical to Altered Response to Gravity ... [Arabidopsis thaliana] GI:4249662; contains Pfam p ...

  5. Arabidopsis CDS blastp result: AK241402 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241402 J065159A02 At4g19070.1 68417.m02810 cadmium-responsive protein / cadmium i...nduced protein (AS8) identical to cadmium induced protein AS8 SP:P42735 from [Arabidopsis thaliana] 3e-11 ...

  6. Arabidopsis CDS blastp result: AK066505 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066505 J013069E21 At2g20410.1 activating signal cointegrator-related similar to ASC-1 (GI:6581 ... milar to Activating signal cointegrator 1 (ASC-1) (Thyroid ... receptor interacting protein 4) (TRIP-4) (Swiss-Pr ...

  7. Arabidopsis CDS blastp result: AK242541 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242541 J080318C07 At3g51730.1 68416.m05672 saposin B domain-containing protein co...ntains Pfam profiles: PF00026 eukaryotic aspartyl protease, PF03489 surfactant protein B, PF05184 saposin-like type B, region 1 3e-36 ...

  8. Arabidopsis CDS blastp result: AK107763 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107763 002-133-A11 At3g51730.1 saposin B domain-containing protein contains Pfam ...profiles: PF00026 eukaryotic aspartyl protease, PF03489 surfactant protein B, PF05184 saposin-like type B, region 1 1e-43 ...

  9. Arabidopsis CDS blastp result: AK242541 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242541 J080318C07 At5g01800.1 68418.m00099 saposin B domain-containing protein co...ntains Pfam profiles: PF00026 eukaryotic aspartyl protease, PF03489 surfactant protein B, PF05184 saposin-like type B, region 1 6e-32 ...

  10. Arabidopsis CDS blastp result: AK067805 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067805 J013119N08 At3g51730.1 saposin B domain-containing protein contains Pfam p...rofiles: PF00026 eukaryotic aspartyl protease, PF03489 surfactant protein B, PF05184 saposin-like type B, region 1 1e-44 ...

  11. Arabidopsis CDS blastp result: AK241812 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241812 J065210K15 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 1e-18 ...

  12. Arabidopsis CDS blastp result: AK288699 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288699 J090061C22 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 2e-35 ...

  13. Arabidopsis CDS blastp result: AK243271 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243271 J100049K04 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 4e-32 ...

  14. Arabidopsis CDS blastp result: AK243428 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243428 J100067L15 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 8e-33 ...

  15. Arabidopsis CDS blastp result: AK241549 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241549 J065176M15 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 5e-29 ...

  16. Arabidopsis CDS blastp result: AK287469 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287469 J043021L20 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 4e-32 ...

  17. Arabidopsis CDS blastp result: AK241615 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241615 J065186D02 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 1e-27 ...

  18. Arabidopsis CDS blastp result: AK241370 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241370 J065154C10 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 1e-30 ...

  19. Arabidopsis CDS blastp result: AK288415 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288415 J090031E07 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 6e-34 ...

  20. Arabidopsis CDS blastp result: AK288487 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288487 J090040H24 At1g66390.1 68414.m07540 myb family transcription factor, putative / product ... ion of anthocyanin pigment ... 2 protein (PAP2) contains Pfam profile: PF00249 my ... 999)); identical to cDNA production of anthocyanin pigment ... 2 protein (PAP2) GI:11935172 1e-30 ...

  1. Arabidopsis CDS blastp result: AK243257 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243257 J100048N01 At1g56280.1 68414.m06469 drought-responsive family protein contains an AT-AC ... 3, potentially contains a frameshift. An alternate model ... provides a translation more consistent with homolo ...

  2. Arabidopsis CDS blastp result: AK059469 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059469 001-028-D11 At4g16340.1 adapter protein SPIKE1 (SPK1) One model ... reflects the alignment ... 96702. There are multiple frame shifts in the gene model ... resulting in a truncated protein. The alternate mo ...

  3. Arabidopsis CDS blastp result: AK243257 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243257 J100048N01 At1g56280.2 68414.m06470 drought-responsive family protein contains an AT-AC ... 3, potentially contains a frameshift. An alternate model ... provides a translation more consistent with homolo ...

  4. Arabidopsis CDS blastp result: AK058386 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK058386 001-014-H12 At4g30100.1 tRNA-splicing endonuclease positive effector-relat...ed contains similarity to SEN1, a positive effector of tRNA-splicing endonuclease [Saccharomyces cerevisiae] gi|172574|gb|AAB63976 1e-42 ...

  5. Arabidopsis CDS blastp result: AK101965 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101965 J033076F14 At2g03690.1 coenzyme Q ... biosynthesis Coq 4 family protein / ubiq uinone biosynt ... hesis Coq 4 family protein contains Pfam profile PF05019: Coe ... nzyme Q ... (ubiq uinone) biosynthesis protein Coq 4 1e-103 ...

  6. Arabidopsis CDS blastp result: AK103795 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103795 J033145P04 At2g03690.1 coenzyme Q ... biosynthesis Coq 4 family protein / ubiq uinone biosynt ... hesis Coq 4 family protein contains Pfam profile PF05019: Coe ... nzyme Q ... (ubiq uinone) biosynthesis protein Coq 4 1e-103 ...

  7. Arabidopsis CDS blastp result: AK108161 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK108161 002-139-G12 At4g36830.1 GNS1/SUR4 membrane family protein weak similarity to long chain polyunsatur...ated fatty acid elongation enzyme [Isochrysis galbana] GI:17226123; contains Pfam profile PF01151: GNS1/SUR4 family 8e-53 ...

  8. Arabidopsis CDS blastp result: AK242290 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242290 J075191E07 At4g13870.1 68417.m02148 Werner Syndrome-like exonuclease (WEX)... contains Pfam profile PF01612: 3'-5' exonuclease; identical to Werner Syndrome-like exonuclease [Arabidopsis thaliana] GP:28195109 gb:AAO33765 1e-20 ...

  9. Arabidopsis CDS blastp result: AK063585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK063585 001-118-A04 At4g13870.2 Werner Syndrome-like exonuclease (WEX) contains Pf...am profile PF01612: 3'-5' exonuclease; identical to Werner Syndrome-like exonuclease [Arabidopsis thaliana] GP:28195109 gb:AAO33765 6e-16 ...

  10. Arabidopsis CDS blastp result: AK242290 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242290 J075191E07 At4g13870.2 68417.m02149 Werner Syndrome-like exonuclease (WEX)... contains Pfam profile PF01612: 3'-5' exonuclease; identical to Werner Syndrome-like exonuclease [Arabidopsis thaliana] GP:28195109 gb:AAO33765 1e-20 ...

  11. Arabidopsis CDS blastp result: AK243230 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243230 J100044L04 At1g19850.1 68414.m02490 transcription factor MONOPTEROS (MP) /... auxin-responsive protein (IAA24) / auxin response factor 5 (ARF5) identical to transcription factor MONOPTEROS (MP/IAA24/ARF5) SP:P93024 from [Arabidopsis thaliana] 2e-65 ...

  12. Arabidopsis CDS blastp result: AK103452 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103452 J033129I11 At1g19850.1 transcription factor MONOPTEROS (MP) / auxin-respon...sive protein (IAA24) / auxin response factor 5 (ARF5) identical to transcription factor MONOPTEROS (MP/IAA24/ARF5) SP:P93024 from [Arabidopsis thaliana] 1e-166 ...

  13. Arabidopsis CDS blastp result: AK318617 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK318617 J100090H20 At1g19850.1 68414.m02490 transcription factor MONOPTEROS (MP) /... auxin-responsive protein (IAA24) / auxin response factor 5 (ARF5) identical to transcription factor MONOPTEROS (MP/IAA24/ARF5) SP:P93024 from [Arabidopsis thaliana] 2e-63 ...

  14. Arabidopsis CDS blastp result: AK068782 [KOME

    Lifescience Database Archive (English)

    Full Text Available containing transmembrane protein 1 [Homo sapiens] GI:4235226; contains Pfam profile PF00036: EF hand 0.0 ... ...AK068782 J013159H18 At1g65540.1 calcium-binding EF hand family protein similar to leucine zipper-EF-hand

  15. Arabidopsis CDS blastp result: AK102710 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102710 J033104J20 At4g24270.2 RNA recognition motif (RRM)-containing protein low similarity to tumor-rejec...tion antigen SART3 [Mus musculus] GI:7637845; contains INTERPRO:IPR000504 RNA-binding region RNP-1 (RNA recognition motif) domain 5e-83 ...

  16. Arabidopsis CDS blastp result: AK111678 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111678 J013158P16 At5g42190.1 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 (At2) / UFO -bi ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  17. Arabidopsis CDS blastp result: AK287832 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287832 J065187F20 At1g30950.1 68414.m03790 unusual floral organ (UFO ) / F-box family protein ( ... ubunit; almost identical to unusual floral organs (UFO )GI:4376159 from [Arabidopsis thaliana] Landsberg-e ...

  18. Arabidopsis CDS blastp result: AK242173 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242173 J075158G19 At5g42190.1 68418.m05135 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 ( ... At2) / UFO -binding protein (UIP2) E3 ubiquitin ligase; skp1b; ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  19. Arabidopsis CDS blastp result: AK102131 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102131 J033085C17 At5g42190.1 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 (At2) / UFO -bi ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  20. Arabidopsis CDS blastp result: AK064628 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064628 002-113-F08 At5g42190.1 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 (At2) / UFO -b ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  1. Arabidopsis CDS blastp result: AK241547 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241547 J065176G22 At1g30950.1 68414.m03790 unusual floral organ (UFO ) / F-box family protein ( ... ubunit; almost identical to unusual floral organs (UFO )GI:4376159 from [Arabidopsis thaliana] Landsberg-e ...

  2. Arabidopsis CDS blastp result: AK242552 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242552 J080319E03 At5g42190.1 68418.m05135 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 ( ... At2) / UFO -binding protein (UIP2) E3 ubiquitin ligase; skp1b; ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  3. Arabidopsis CDS blastp result: AK241794 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241794 J065208D18 At5g42190.1 68418.m05135 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 ( ... At2) / UFO -binding protein (UIP2) E3 ubiquitin ligase; skp1b; ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  4. Arabidopsis CDS blastp result: AK073278 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073278 J033025L08 At5g42190.1 E3 ubiquitin ligase SCF complex subunit SKP1/ASK1 (At2) / UFO -bi ... family, tetramerisation domain; identical to cDNA UFO ... binding protein UIP2 mRNA, partial cds GI:3719210 ...

  5. Arabidopsis CDS blastp result: AK242616 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 2e-34 ... ...AK242616 J090017C19 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  6. Arabidopsis CDS blastp result: AK242098 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 3e-58 ... ...AK242098 J075143H11 At2g29380.1 68415.m03569 protein phosphatase 2C, putative / PP2C, putati

  7. Arabidopsis CDS blastp result: AK243539 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 3e-20 ... ...AK243539 J100078G04 At2g29380.1 68415.m03569 protein phosphatase 2C, putative / PP2C, putati

  8. Arabidopsis CDS blastp result: AK071996 [KOME

    Lifescience Database Archive (English)

    Full Text Available ontains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 1e-33 ... ...AK071996 J013091F23 At2g29380.1 protein phosphatase 2C, putative / PP2C, putative c

  9. Arabidopsis CDS blastp result: AK242616 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 4e-67 ... ...AK242616 J090017C19 At2g29380.1 68415.m03569 protein phosphatase 2C, putative / PP2C, putati

  10. Arabidopsis CDS blastp result: AK242846 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 9e-12 ... ...AK242846 J090071I10 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  11. Arabidopsis CDS blastp result: AK241162 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241162 J065116A05 At5g54800.1 68418.m06826 glucose-6-phosphate/phosphate translocator, putative identic...al to glucose 6 phosphate/phosphate translocator [Arabidopsis thaliana] gi|7229675|gb|AAF42936 2e-11 ...

  12. Arabidopsis CDS blastp result: AK242098 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 3e-22 ... ...AK242098 J075143H11 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  13. Arabidopsis CDS blastp result: AK287695 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 2e-31 ... ...AK287695 J065129B08 At2g29380.1 68415.m03569 protein phosphatase 2C, putative / PP2C, putati

  14. Arabidopsis CDS blastp result: AK243041 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 4e-31 ... ...AK243041 J100008G07 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  15. Arabidopsis CDS blastp result: AK242846 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 2e-12 ... ...AK242846 J090071I10 At2g29380.1 68415.m03569 protein phosphatase 2C, putative / PP2C, putati

  16. Arabidopsis CDS blastp result: AK243539 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 6e-34 ... ...AK243539 J100078G04 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  17. Arabidopsis CDS blastp result: AK242576 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 3e-22 ... ...AK242576 J090009A15 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  18. Arabidopsis CDS blastp result: AK289111 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 5e-20 ... ...AK289111 J090096N14 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  19. Arabidopsis CDS blastp result: AK063334 [KOME

    Lifescience Database Archive (English)

    Full Text Available contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 3e-85 ... ...AK063334 001-114-A05 At2g29380.1 protein phosphatase 2C, putative / PP2C, putative

  20. Arabidopsis CDS blastp result: AK289248 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK289248 J100079D02 At5g54800.1 68418.m06826 glucose-6-phosphate/phosphate translocator, putative identic...al to glucose 6 phosphate/phosphate translocator [Arabidopsis thaliana] gi|7229675|gb|AAF42936 7e-19 ...

  1. Arabidopsis CDS blastp result: AK243041 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 3e-26 ... ...AK243041 J100008G07 At2g29380.1 68415.m03569 protein phosphatase 2C, putative / PP2C, putati

  2. Arabidopsis CDS blastp result: AK108969 [KOME

    Lifescience Database Archive (English)

    Full Text Available contains PF00481: Protein phosphatase 2C domain; similar to protein phpsphatase 2C (PP2C) (GI:7768151) [Fagus sylvatica]. 1e-61 ... ...AK108969 002-153-D11 At2g29380.1 protein phosphatase 2C, putative / PP2C, putative

  3. Arabidopsis CDS blastp result: AK287695 [KOME

    Lifescience Database Archive (English)

    Full Text Available ve contains PF00481: Protein phosphatase 2C domain; identical to protein phosphatase 2C (GI:4587992) [Arabidopsis thaliana] 3e-81 ... ...AK287695 J065129B08 At2g40180.1 68415.m04941 protein phosphatase 2C, putative / PP2C, putati

  4. Arabidopsis CDS blastp result: AK242756 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242756 J090051D19 At4g14330.1 68417.m02207 phragmoplast-associated kinesin-relate...d protein 2 (PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 4e-22 ...

  5. Arabidopsis CDS blastp result: AK242767 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242767 J090053D16 At4g14330.1 68417.m02207 phragmoplast-associated kinesin-relate...d protein 2 (PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 1e-20 ...

  6. Arabidopsis CDS blastp result: AK059635 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059635 001-031-A08 At4g14330.1 phragmoplast-associated kinesin-related protein 2 ...(PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 6e-18 ...

  7. Arabidopsis CDS blastp result: AK287457 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287457 J043019L17 At4g14330.1 68417.m02207 phragmoplast-associated kinesin-relate...d protein 2 (PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 3e-24 ...

  8. Arabidopsis CDS blastp result: AK242681 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242681 J090032N04 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  9. Arabidopsis CDS blastp result: AK243413 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243413 J100065P17 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  10. Arabidopsis CDS blastp result: AK288723 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288723 J090063A13 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  11. Arabidopsis CDS blastp result: AK318529 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK318529 J065162I20 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  12. Arabidopsis CDS blastp result: AK100268 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100268 J023065A22 At2g31800.1 ankyrin protein kinase, putative similar to ankyrin-kinase [Medi ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  13. Arabidopsis CDS blastp result: AK241519 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241519 J065170E12 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  14. Arabidopsis CDS blastp result: AK099756 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099756 J013093B21 At2g31800.1 ankyrin protein kinase, putative similar to ankyrin-kinase [Medi ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  15. Arabidopsis CDS blastp result: AK243690 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243690 J100090O16 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  16. Arabidopsis CDS blastp result: AK071922 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071922 J013072M01 At2g31800.1 ankyrin protein kinase, putative similar to ankyrin-kinase [Medi ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  17. Arabidopsis CDS blastp result: AK243248 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243248 J100047K09 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  18. Arabidopsis CDS blastp result: AK287946 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287946 J075022P19 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  19. Arabidopsis CDS blastp result: AK243345 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243345 J100060A02 At2g31800.1 68415.m03882 ankyrin protein kinase, putative similar to ankyrin ... rotein 10 (CBL10) GI:29150247; blastp match of 67% identity ... and 1.9e-200 P-value to GP|18700701|gb|AAL78674.1| ...

  20. Arabidopsis CDS blastp result: AK243048 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243048 J100010D20 At1g07370.1 68414.m00786 proliferating cell nuclear ... antigen 1 (PCNA1) identi ... cal to SP|Q9M7Q7 Proliferating cellular nuclear ... antigen 1 (PCNA 1) {Arabidopsis thaliana}; nearly ... identical to SP|Q43124 Proliferating cell nuclear ... antigen (PCNA) {Brassica napus}; contains Pfam pro ...

  1. Arabidopsis CDS blastp result: AK071591 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071591 J023105C08 At2g29570.1 proliferating cell nuclear ... antigen 2 (PCNA2) identical to SP|Q9Z ... W35 Proliferating cell nuclear ... antigen 2 (PCNA 2) {Arabidopsis thaliana}; nearly ... identical to SP|Q43124 Proliferating cell nuclear ... antigen (PCNA) {Brassica napus}; contains Pfam pro ...

  2. Arabidopsis CDS blastp result: AK243048 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243048 J100010D20 At2g29570.1 68415.m03591 proliferating cell nuclear ... antigen 2 (PCNA2) identi ... cal to SP|Q9ZW35 Proliferating cell nuclear ... antigen 2 (PCNA 2) {Arabidopsis thaliana}; nearly ... identical to SP|Q43124 Proliferating cell nuclear ... antigen (PCNA) {Brassica napus}; contains Pfam pro ...

  3. Arabidopsis CDS blastp result: AK102303 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102303 J033089O13 At1g32230.2 WWE domain-containing protein / ceo protein, putative (CEO...) contains Pfam domain, PF02825: WWE domain; identical to cDNA for ceo protein (ceo gene) GI:11044956 9e-37 ...

  4. Arabidopsis CDS blastp result: AK099725 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099725 J013089B18 At1g32230.2 WWE domain-containing protein / ceo protein, putative (CEO...) contains Pfam domain, PF02825: WWE domain; identical to cDNA for ceo protein (ceo gene) GI:11044956 2e-53 ...

  5. Arabidopsis CDS blastp result: AK065783 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065783 J013038L18 At1g32230.2 WWE domain-containing protein / ceo protein, putative (CEO...) contains Pfam domain, PF02825: WWE domain; identical to cDNA for ceo protein (ceo gene) GI:11044956 4e-34 ...

  6. Arabidopsis CDS blastp result: AK072769 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK072769 J023139M21 At1g32230.1 WWE domain-containing protein / ceo protein, putative (CEO...) contains Pfam domain, PF02825: WWE domain; identical to cDNA for ceo protein (ceo gene) GI:11044956 4e-66 ...

  7. Arabidopsis CDS blastp result: AK240908 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240908 J065036M21 At5g60110.1 68418.m07536 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806: Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  8. Arabidopsis CDS blastp result: AK240908 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240908 J065036M21 At5g59280.1 68418.m07428 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806: Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  9. Arabidopsis CDS blastp result: AK240908 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240908 J065036M21 At1g78160.1 68414.m09108 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  10. Arabidopsis CDS blastp result: AK240908 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240908 J065036M21 At1g35850.1 68414.m04454 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806: Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  11. Arabidopsis CDS blastp result: AK287668 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287668 J065118D12 At3g20250.1 68416.m02565 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  12. Arabidopsis CDS blastp result: AK287668 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287668 J065118D12 At1g78160.1 68414.m09108 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  13. Arabidopsis CDS blastp result: AK242989 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242989 J090095B13 At3g20250.1 68416.m02565 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  14. Arabidopsis CDS blastp result: AK240908 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240908 J065036M21 At3g20250.1 68416.m02565 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  15. Arabidopsis CDS blastp result: AK106885 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK106885 002-118-F08 At1g78160.1 pumilio /Puf RNA-binding domain-containing protein contains Pfam ... profile: PF00806 Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  16. Arabidopsis CDS blastp result: AK240908 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240908 J065036M21 At5g60180.1 68418.m07544 pumilio /Puf RNA-binding domain-containing protein c ... ontains Pfam profile: PF00806: Pumilio -family RNA binding domains (aka PUM-HD, Pumilio ... ho ...

  17. Arabidopsis CDS blastp result: AK241265 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241265 J065132C02 At3g19450.1 68416.m02466 cinnamyl-alcohol dehydrogenase (CAD ) identical to S ... 523 Cinnamyl-alcohol dehydrogenase (EC 1.1.1.195) (CAD ) [Arabidopsis thaliana] 1e-81 ...

  18. Arabidopsis CDS blastp result: AK105739 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105739 001-202-A05 At3g19450.1 cinnamyl-alcohol dehydrogenase (CAD ) identical to SP|P48523 Cin ... namyl-alcohol dehydrogenase (EC 1.1.1.195) (CAD ) [Arabidopsis thaliana] 2e-46 ...

  19. Arabidopsis CDS blastp result: AK243022 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243022 J100001E20 At3g19450.1 68416.m02466 cinnamyl-alcohol dehydrogenase (CAD ) identical to S ... 523 Cinnamyl-alcohol dehydrogenase (EC 1.1.1.195) (CAD ) [Arabidopsis thaliana] 4e-64 ...

  20. Arabidopsis CDS blastp result: AK287708 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287708 J065132C02 At3g19450.1 68416.m02466 cinnamyl-alcohol dehydrogenase (CAD ) identical to S ... 523 Cinnamyl-alcohol dehydrogenase (EC 1.1.1.195) (CAD ) [Arabidopsis thaliana] 1e-81 ...

  1. Arabidopsis CDS blastp result: AK099373 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK099373 J033063M10 At5g27820.1 ribosomal protein L18 family protein similar to SP|P52863 50S ri ... bosomal protein L18 [Aeromonas ... proteolytica] {Vibrio proteolyticus} 6e-44 ...

  2. Arabidopsis CDS blastp result: AK071362 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071362 J023093M09 At5g27820.1 ribosomal protein L18 family protein similar to SP|P52863 50S ri ... bosomal protein L18 [Aeromonas ... proteolytica] {Vibrio proteolyticus} 2e-42 ...

  3. Arabidopsis CDS blastp result: AK063884 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK063884 001-122-F11 At5g27820.1 ribosomal protein L18 family protein similar to SP|P52863 50S r ... ibosomal protein L18 [Aeromonas ... proteolytica] {Vibrio proteolyticus} 6e-44 ...

  4. Arabidopsis CDS blastp result: AK100867 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100867 J023124E13 At2g29640.1 josephin family protein contains Pfam domain PF02099: Jose...phin; similar to Josephin-like protein (Swiss-Prot:O82391) [Arabidopsis thaliana] 7e-59 ...

  5. Arabidopsis CDS blastp result: AK065851 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065851 J013041L15 At1g79010.1 NADH-ubiquinone oxidoreductase 23 kDa subunit, mitochondrial (TY ... ursor (EC 1.6.5.3) (EC 1.6.99.3) (Complex I-23KD) (CI -23KD) (Complex I- 28.5KD) (CI -28.5KD) {Arabidopsis ...

  6. Arabidopsis CDS blastp result: AK119532 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119532 001-203-F01 At1g79010.1 NADH-ubiquinone oxidoreductase 23 kDa subunit, mitochondrial (T ... ursor (EC 1.6.5.3) (EC 1.6.99.3) (Complex I-23KD) (CI -23KD) (Complex I- 28.5KD) (CI -28.5KD) {Arabidopsis ...

  7. Arabidopsis CDS blastp result: AK240869 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK240869 J065024G23 At3g06310.1 68416.m00725 NADH-ubiquinone oxidoreductase 19 kDa subunit (NDUF ... bunit (EC 1.6.5.3) (EC 1.6.99.3) (Complex I-19KD) (CI -19KD) (Complex I-PGIV) (CI -PGIV) (Swiss-Prot:P5197 ...

  8. Arabidopsis CDS blastp result: AK243057 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243057 J100013P13 At3g62060.1 68416.m06973 pectinacetylesterase family protein similar to pectin...acetylesterase precursor GI:1431629 from [Vigna radiata]; contains Pfam profile: PF03283 pectinacetylesterase 1e-103 ...

  9. Arabidopsis CDS blastp result: AK243512 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243512 J100075C18 At4g16280.3 68417.m02471 flowering time ... control protein / FCA gamma (FCA) id ... entical to SP|O04425 Flowering time ... control protein FCA {Arabidopsis thaliana}; four a ...

  10. Arabidopsis CDS blastp result: AK243512 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243512 J100075C18 At4g16280.2 68417.m02470 flowering time ... control protein / FCA gamma (FCA) id ... entical to SP|O04425 Flowering time ... control protein FCA {Arabidopsis thaliana}; four a ...

  11. Arabidopsis CDS blastp result: AK066361 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK066361 J013063L05 At4g39520.1 GTP-binding protein, putative similar to SP|Q9Y295 Developmental ... ly regulated GTP-binding protein 1 (DRG ... 1) {Homo sapiens}; contains Pfam profiles PF02824: ...

  12. Arabidopsis CDS blastp result: AK100600 [KOME

    Lifescience Database Archive (English)

    Full Text Available n similar to J-Domain (Residues 1-77) Of The Escherichia Coli N-Terminal Fragment (Residues 1-104) Of The Mo...AK100600 J023107C09 At1g77930.2 DNAJ heat shock N-terminal domain-containing protei

  13. Arabidopsis CDS blastp result: AK242890 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242890 J090079L19 At5g16910.1 68418.m01982 cellulose synthase family protein similar to gi:2827143 cellulo...se synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 1e-130 ...

  14. Arabidopsis CDS blastp result: AK120054 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK120054 J013000L05 At1g55850.1 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-5 [gi:9622882] from Zea mays 1e-148 ...

  15. Arabidopsis CDS blastp result: AK242585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242585 J090010M20 At1g02730.1 68414.m00226 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-4 [gi:9622880] from Zea mays 7e-27 ...

  16. Arabidopsis CDS blastp result: AK111344 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK111344 002-181-F12 At1g55850.1 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-5 [gi:9622882] from Zea mays 2e-15 ...

  17. Arabidopsis CDS blastp result: AK242585 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242585 J090010M20 At5g16910.1 68418.m01982 cellulose synthase family protein similar to gi:2827143 cellulo...se synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 2e-65 ...

  18. Arabidopsis CDS blastp result: AK110534 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK110534 002-168-A07 At5g16910.1 cellulose synthase family protein similar to gi:2827143 cellulose... synthase catalytic subunit, Arabidopsis thaliana, gi:9622886 cellulose synthase-7 from Zea mays 1e-114 ...

  19. Arabidopsis CDS blastp result: AK242601 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK242601 J090014G03 At1g02730.1 68414.m00226 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-4 [gi:9622880] from Zea mays 0.0 ...

  20. Arabidopsis CDS blastp result: AK102766 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102766 J033107E04 At1g55850.1 cellulose synthase family protein similar to cellulose... synthase catalytic subunit [gi:13925881] from Nicotiana alata, cellulose synthase-5 [gi:9622882] from Zea mays 0.0 ...