Protein Information

ID 12
Name caspase 3
Synonyms Apopain; CASP 3; CASP3; CPP 32; CPP32; CPP32B; Caspase 3; Caspase 3 precursor…

Compound Information

ID 1822
Name sodium cyanide
CAS sodium cyanide (Na(CN))

Reference

PubMed Abstract RScore(About this table)
16859701 Hsieh YC, Yu HP, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH: Upregulation of mitochondrial respiratory complex IV by estrogen receptor-beta is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage. J Mol Cell Cardiol. 2006 Sep;41(3):511-21. Epub 2006 Jul 21.
Our recent study showed that estrogen receptor (ER) beta plays a major role in mediating the salutary effects of 17beta-estradiol (E2) on cardiac function following trauma-hemorrhage (T-H). E2 is known to regulate mitochondrial DNA (mtDNA)-encoded genes including the mitochondrial respiratory complex (MRC) proteins. Depressed MRC activity has been reported to promote the release of cytochrome c from mitochondria and induce apoptosis. We hypothesized that E2 and ERbeta-mediated cardioprotection following T-H is dependent on mtDNA transcription encoding for MRC activity. To test this, male rats underwent T-H (mean BP 40 mm Hg approximately 90 min, then resuscitation). During resuscitation, rats received either ERalpha agonist propylpyrazole triol (PPT; 5 microg/kg), ERbeta agonist diarylpropionitrile (DPN; 5 microg/kg), E2 (50 microg/kg), or vehicle (10% DMSO). Another group of rats received mitochondrial respiratory complex-IV (MRC-IV) inhibitor sodium cyanide (SCN; 6 mg/kg) with or without DPN. The results indicated that 24 h after T-H, cardiac functions were depressed in the vehicle-treated but were normal in the DPN-treated rats. Moreover, E2 or DPN treatment after T-H normalized cardiac mitochondrial ERbeta expression and increased mitochondrial ERbeta DNA-binding activity. This was accompanied by an increase in MRC-IV gene expressions and activity, while MRC-I gene expression remained unchanged. Inhibition of MRC-IV in DPN-treated T-H rats by SCN abolished the DPN-mediated cardioprotection, ATP production, mitochondrial cytochrome c release, caspase-3 cleavage, and apoptosis. Thus, E2 and ERbeta-mediated cardioprotection following T-H appears to be mediated via mitochondrial ERbeta-dependent MRC-IV activity and inhibition of mitochondrial apoptotic signaling pathways.
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