Upregulation of mitochondrial respiratory complex IV by estrogen receptor-β is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage
Upregulation of mitochondrial respiratory complex IV by estrogen receptor-β is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage
复制标题
DOI：
10.1016/j.yjmcc.2006.06.001
复制
发表时间：
2006-09-01
影响因子：
5
通讯作者：
Chaudry, Irshad H.
中科院分区：
文献类型：
--
作者：
Hsieh, Ya-Ching;Yu, Huang-Ping;Chaudry, Irshad H.
我们最近的研究表明，雌激素受体(ER) β在介导17 - β -雌二醇（E2）对创伤性出血（T-H）后心功能的有益作用中起主要作用。已知E2调节线粒体DNA （mtDNA）编码基因，包括线粒体呼吸复合体（MRC）蛋白。据报道，MRC活性降低可促进线粒体细胞色素c的释放并诱导细胞凋亡。我们假设T-H后E2和ER β介导的心脏保护依赖于编码MRC活性的mtDNA转录。为了验证这一点，雄性大鼠进行了T-H（平均血压40毫米汞柱，类似于90分钟，然后复苏）。复苏期间，大鼠分别给予内质网α激动剂丙基吡唑三醇（PPT, 5 μ g/kg）、内质网激动剂二酰丙腈（DPN, 5 μ g/kg）、E2 （50 μ g/kg）或载药（10% DMSO）。另一组大鼠给予线粒体呼吸复合物iv （MRC-IV）抑制剂氰化钠（SCN; 6 mg/kg），伴或不伴DPN。结果显示，T-H后24 h，给药大鼠心功能下降，而dpn给药大鼠心功能正常。此外，T-H后E2或DPN治疗使心肌线粒体ER β表达正常化，并增加线粒体ER β dna结合活性。这伴随着MRC-IV基因表达和活性的增加，而MRC-I基因表达保持不变。SCN抑制dpn处理的T-H大鼠的MRC-IV，可消除dpn介导的心脏保护、ATP产生、线粒体细胞色素c释放、caspase-3切割和细胞凋亡。因此，T-H后E2和内质网β介导的心脏保护似乎是通过线粒体内质网β依赖的MRC-IV活性和线粒体凋亡信号通路的抑制介导的。(c) 2006爱思唯尔公司版权所有。
Our recent study showed that estrogen receptor (ER) beta plays a major role in mediating the salutary effects of 17 beta-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 ER beta-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 similar to 90 min, then resuscitation). During resuscitation, rats received either ER alpha agonist propylpyrazole triol (PPT; 5 mu g/kg), ER agonist diarylpropionitrile (DPN; 5 mu g/kg), E2 (50 mu g/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 ER beta expression and increased mitochondrial ER beta 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 ER beta-mediated cardioprotection following T-H appears to be mediated via mitochondrial ER beta-dependent MRC-IV activity and inhibition of mitochondrial apoptotic signaling pathways. (c) 2006 Elsevier Inc. All rights reserved.