Apoptotic signaling induces hyperpermeability following hemorrhagic shock
Apoptotic signaling induces hyperpermeability following hemorrhagic shock
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DOI：
10.1152/ajpheart.01337.2006
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Cao, Xiaobo
中科院分区：
文献类型：
--
作者：
Childs, Ed W.;Tharakan, Binu;Cao, Xiaobo
失血性休克(HS)破坏内皮细胞屏障，导致严重的微血管高通透性。最近的研究也表明，凋亡信号级联的激活与内皮功能障碍有关。这可能会导致高渗透性。在此，我们报道了线粒体“内在”途径参与了大鼠微血管高通透性的形成。HS导致线粒体内源性途径的激活，表现在促凋亡的BAK家族成员BAK增加，线粒体细胞色素c释放到细胞质中，以及caspase-3的激活。这。BAK(BH3)的体内致死转移。导致高通透性(如活体显微镜所见)。线粒体细胞色素c释放到细胞质中。和caspase-3的激活。反之，BAK(BH3)突变体对高通透性无影响。在一起。这些结果表明，线粒体固有的凋亡途径参与了HS诱导的高通透性，减弱这一途径可能提供了一种保护血管屏障完整性的替代策略。
Hemorrhagic shock (HS) disrupts the endothelial cell barrier, resulting ill microvascular hyperpermeability. Recent studies have also demonstrated that activation of the apoptotic signaling cascade is involved in endothelial dysfunction. which may result in hyperpermeability. Here we report involvement of the mitochondrial "intrinsic" pathway in microvascular hyperpermeability foll:)wing HS in rats. HS resulted in the activation of the mitochondrial intrinsic pathway, as is evident from in increase in the proapoptotic Bcl-2 family member BAK, release of mitochondrial cytochrome c into the cytoplasm, and activation of caspase-3. This. along,vith the ill vivo transfection of the proapoptotic peptide BAK (BH3). resulted in hyperpermeability (as Visualized by intravital microscopy). release of mitochondrial cytochrome c into the cytoplasm. and activation of caspase-3. Conversely, transfection of the BAK (BH3) Mutant had no effect on hyperpermeability. Together. these results demonstrate involvement of the mitochondrial intrinsic apoptotic pathway in HS-induced hyperpermeability and that the attenuation of this pat hway may provide an alternative strategy ill preserving vascular barrier integrity.