Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine whether activation of ATP-sensitive K+ (KATP) channels with diazoxide (DIZ) is able to prevent the cleavage of cytosolic mu-calpain and abrogate the elevation of nuclear c-Fos and c-Jun protein (c-Fos, c-Jun) expressions after hypoxic-ischemia (HI) in brain. The model of hypoxic-ischemic brain injury (HIBI) was made in the 7-day-old Sprague-Dawley (SD) rats by left carotid arterial ligation and hypoxia (8% oxygen). DIZ was injected into the left lateral ventricle (5 microl, 1 mg/ml) before or post-hypoxic-ischemia (HI) insults. Western blot and computer image processing were used to detect the integrated density of nuclear c-Fos and c-Jun at 4 h and cleavage of cytosolic mu-calpain at 24 h after HI insults from cerebral cortical and hippocampal samples. Compared with HI controls (c-Fos=30.37+/-7.39 from cortical samples, 58.61+/-3.64 from hippocampal samples; c-Jun=52.48+/-14.23 from cortical samples, 35.55+/-4.73 from hippocampal samples), there was a significant down-regulation of c-Fos and c-Jun expressions from cortical and hippocampal samples in rats treated with DIZ before (c-Fos=11.10+/-4.64 from cortical samples, 4.82+/-3.38 from hippocampal samples; c-Jun=19.01+/-5.29 from cortical samples, 35.55+/-4.73 from hippocampal samples) or post- (c-Fos=18.81+/-7.93 from cortical samples, 11.33+/-7.05 from hippocampal samples; c-Jun=24.64+/-10.01 from cortical samples, 19.75+/-3.47 from hippocampal samples) HI insults. Furthermore, the ratio of 76 kD/80 kD of mu-calpain was down-regulated from cortical and hippocampal samples in rats treated with DIZ before or post-HI insults, demonstrating a significant difference compared with that observed in HI controls. Finally, the increase in DNA fragments caused by the HI injury was decreased or eliminated by the treatment with DIZ. These data suggests that activation of KATP channels by DIZ reduces the degree of mu-calpain proteolysis, and c-Fos and c-Jun expressions in immature brain may contribute to the neuroprotection of K(ATP) channel openers against HIBI.
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PMID:Activation of ATP-sensitive potassium channels prevents the cleavage of cytosolic mu-calpain and abrogates the elevation of nuclear c-Fos and c-Jun expressions after hypoxic-ischemia in neonatal rat brain. 1566 68

Both calpain activation and endoplasmic reticulum (ER) stress are implicated in ischemic heart injury. However, the role of calpain in ER stress remains largely elusive. This study investigated whether calpain activation causes ER stress, thereby mediating cardiomyocyte apoptosis in an in vitro model of hypoxia/re-oxygenation (H/R). In neonatal mouse cardiomyocytes and rat cardiomyocyte-like H9c2 cells, up-regulation of calpain-1 sufficiently induced ER stress, c-Jun N-terminal protein kinase1/2 (JNK1/2) activation and apoptosis. Inhibition of ER stress or JNK1/2 prevented apoptosis induced by calpain-1. In an in vitro model of H/R-induced injury in cardiomyocytes, H/R was induced by a 24-hour hypoxia followed by a 24-hour re-oxygenation. H/R activated calpain-1, induced ER stress and JNK1/2 activation, and triggered apoptosis. Inhibition of calpain and ER stress blocked JNK1/2 activation and prevented H/R-induced apoptosis. Furthermore, blockade of JNK1/2 signaling inhibited apoptosis following H/R. The role of calpain in ER stress was also demonstrated in an in vivo model of ischemia/reperfusion using transgenic mice over-expressing calpastatin. In summary, calpain-1 induces ER stress and JNK1/2 activation, thereby mediating apoptosis in cardiomyocytes. Accordingly, inhibition of calpain prevents ER stress, JNK1/2 activation and apoptosis in H/R-induced cardiomyocytes. Thus, ER stress/JNK1/2 activation may represent an important mechanism linking calpain-1 to ischemic injury.
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PMID:Calpain-1 induces endoplasmic reticulum stress in promoting cardiomyocyte apoptosis following hypoxia/reoxygenation. 2566 Apr 47