Disease relevance of calpeptin

• The toxicity in E47 cells mirrored calpain activation and was inhibited by calpeptin, suggesting that calpain activation plays a causal role in toxicity [1].
• Pulmonary artery endothelial cells (PAEC) were exposed to normoxia or hypoxia (0% O(2)-95% N(2)-5% CO(2)) in the presence and absence of calpain inhibitor I or calpeptin, after which endothelial nitric oxide synthase (eNOS) activity and protein content were assayed [2].
• The results imply that calpeptin may serve as a therapeutic agent for preventing motoneuron degeneration, which occurs in amyotrophic lateral sclerosis and spinal cord injury [3].
• Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively [4].
• Calpeptin (1 mg/kg), a calpain inhibitor, attenuated the deterioration of renal function to the same extent as 0.1 mg/kg PSI, but no significant difference was observed between the untreated and calpeptin-treated acute renal failure groups [5].

High impact information on calpeptin

• Inhibition of this proteolytic activity by calpeptin, a calpain inhibitor, abolishes growth cone formation [6].
• In addition, calpeptin or EGTA inhibited not only calpain mu activation but also cytoskeletal protein degradation and bleb formation [7].
• METHODS: Hepatocytes from Wistar rats were injured with tertbutyl hydroperoxide in the presence or absence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or a specific calpain inhibitor, calpeptin (Z-Leu-nLeu-H) [7].
• Similarly to calpeptin, okadaic acid inhibits ICA512 proteolysis and insulin secretion [8].
• The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP(-/-) mice [9].

Chemical compound and disease context of calpeptin

• The decline in Delta(Psi)(m) and the toxicity in both MEM and SMEM were inhibited by alpha-tocopherol and cyclosporin A, while the calpain inhibitor calpeptin was only effective in MEM [10].
• Hypoxia caused selective cleavage of troponin I (TnI), which could be suppressed by either nifedipine or calpeptin [11].
• METHODS: In halothane-anesthetized rats treated with saline, dimethyl sulfoxide (DMSO), or the synthetic calpain inhibitor calpeptin (3,500 microg), a subdural balloon catheter was inflated to induce intracranial hypertension [12].

Biological context of calpeptin

• Conversely, poly(ADP)ribose polymerase (PARP) was cleaved in a pattern indicative of calpain activation, and the calpain inhibitor calpeptin abrogated SAHA-induced cell death [13].
• Calpain activation and subsequent apoptosis were inhibited by calpeptin and PD150606, two calpain inhibitors with different modes of action [14].
• Platelet activation also led to adducin proteolysis; inhibition by calpeptin suggests that the protease was calpain [15].
• Platelet aggregation detected turbidometrically was decreased in the presence of staurosporine and was completely inhibited by calpeptin [15].
• Flow cytometric analysis of DNA content and synthesis in BASMCs treated with TPI-1 or calpeptin additionally revealed the presence of a distinct cell cycle block in the G2-M compartment [16].

Anatomical context of calpeptin

• Experiments performed with intact erythrocytes in the presence of the SHP-2 inhibitor calpeptin suggest that, once recruited to Tyr-phosphorylated band 3, the tyrosine phosphatase dephosphorylates the protein [17].
• Calpeptin induced stress fiber formation in both forskolin-treated REF-52 fibroblasts and serum-starved Swiss 3T3 fibroblasts [18].
• We employed a commonly used inhibitor of calpain, calpeptin, to examine a role for this protease in the reorganization of the cytoskeleton under a variety of conditions [18].
• Furthermore, the expression of p12(I) in Jurkat T cells using lentiviral vectors enhanced LFA-1-mediated cell adhesion, which was inhibited by the calcium chelator BAPTA-AM, the calcium channel blocker SK&F 96365, and calpeptin, an inhibitor of the calcium-dependent protease calpain [19].
• In contrast, after the development of contractile activity, dystrophic mdx myotubes had abnormally high levels of hydrolysis that were dependent on external calcium and that could be abolished by calpeptin, an inhibitor of calpain [20].

Associations of calpeptin with other chemical compounds

• Thrombin-induced changes in morphology were assessed by confocal microscopy with fluorescein phalloidin and were not prevented by staurosporine or calpeptin [15].
• While calpeptin did not affect cisplatin-induced modulation of Bak to its proapoptotic conformation, a dominant-negative mutant of MEKK1 (dnMEKK) inhibited Bak modulation. dnMEKK did not, however, block Bid cleavage [14].
• In addition, the proteolysis of cortactin was abolished by treating platelets before but not after collagen stimulation with EGTA or calpeptin [21].
• The proteolysis of these proteins was dependent on the presence of extracellular calcium and was specifically inhibited by pretreating platelets with the membrane-permeable calpain inhibitors calpeptin, E64d, and MDL 28,170, but not with the membrane-impermeable inhibitors leupeptin, E64, and calpastatin [22].
• Consistent with this, our recent studies have demonstrated the existence of a protein tyrosine phosphatase (PTPase), sensitive to the dipeptide aldehyde calpeptin, acting upstream of RhoA [5] [23].

Gene context of calpeptin

• Down-regulation of cyclin D1 and ER alpha by PPARgamma agonists was inhibited in cells cotreated with the proteasome inhibitors MG132 and PSII, but not in cells cotreated with the protease inhibitors calpain II and calpeptin [24].
• Cell-permeable calpain inhibitors, including calpastatin and calpeptin, were sufficient to suppress RANKL-supported osteoclastogenesis based on decreased expression of the osteoclastogenic marker, matrix metalloproteinase 9, and the generation of tartrate-resistant acid phosphatase-positive multinucleated cells in both cell types [25].
• Enzymatic inhibition of calpain by calpeptin precluded AIF release, demonstrating that proteolytic activity was required for release [26].
• Proteasome inhibitors but not calpeptin prevented the catalase-mediated decrease of p53 content [27].
• Cell permeable inhibitors of calpain, ALLnM, E64 and calpeptin that block Fas ligand-Fas-mediated death in T cells, blocked etoposide-induced nuclear damage, loss of mitochondrial integrity and cell lysis [28].

Analytical, diagnostic and therapeutic context of calpeptin

• Moreover, inhibition of calpain by calpeptin prior to axotomy inhibits growth cone formation [29].
• 5. Incubation of the cell culture for 3-5 days from the onset of induction of myotube formation with the membrane permeable protease inhibitor, calpeptin (50 microM) abolished the rise in [Ca2+]c in mdx myotubes upon exposure to hypo-osmotic shock [30].
• In the present experiments, treatment of rats with one of the calpain inhibitors calpeptin or BN82270 inhibited protein breakdown in muscles from rats made septic by cecal ligation and puncture [31].
• Myoglobinuria appeared immediately after reperfusion, and was also attenuated by calpeptin [32].
• In the present study, the possible involvement of calpain in the lysis was investigated in a MNMS animal model employing a cell permeable calpain antagonist calpeptin [32].

References