Puerarin induces mitochondria-dependent apoptosis in hypoxic human pulmonary arterial smooth muscle cells.
Puerarin induces mitochondria-dependent apoptosis in hypoxic human pulmonary arterial smooth muscle cells.
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DOI：
10.1371/journal.pone.0034181
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Chen C;Chen C;Wang Z;Wang L;Yang L;Ding M;Ding C;Sun Y;Lin Q;Huang X;Du X;Zhao X;Wang C
缺氧肺动脉高压（PAH）的肺血管内侧肥大部分是由肺动脉平滑肌细胞（PASMCs）凋亡减少引起的。葛根素，一种从中药葛根中纯化的异黄酮，在动物模型中改善慢性缺氧多环芳烃。本文研究葛根素对缺氧人PASMCs （HPASMCs）细胞凋亡的影响，并探讨其可能的机制。HPASMCs在加葛根素和不加葛根素的常氧或缺氧（5% O2）条件下培养24小时。用血细胞计或细胞计数试剂盒测定细胞数量和活力。采用TUNEL试验、罗丹明-123 （R-123）荧光、比色法、western blots、免疫组织化学染色和RT-PCR检测细胞凋亡。缺氧抑制线粒体依赖性细胞凋亡，促进HPASMC生长。相反，葛根素（50µM及以上）干预后，细胞生长受到抑制，并出现凋亡。在缺氧HPASMCs中，葛根素诱导的凋亡伴随着线粒体膜电位降低、线粒体细胞色素c释放、caspase-9激活和Bcl-2下调，同时Bax上调。葛根素通过线粒体依赖途径促进缺氧HPASMCs的凋亡。这些结果提示葛根素与临床低氧性肺动脉高压治疗相关的新机制。
Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial hypertension (PAH) is caused in part by decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Puerarin, an isoflavone purified from the Chinese medicinal herb kudzu, ameliorates chronic hypoxic PAH in animal models. Here we investigated the effects of puerarin on apoptosis of hypoxic human PASMCs (HPASMCs), and to determine the possible underlying mechanisms. HPASMCs were cultured for 24 h in normoxia or hypoxia (5% O2) conditions with and without puerarin. Cell number and viability were determined with a hemacytometer or a cell counting kit. Apoptosis was detected with a TUNEL test, rhodamine-123 (R-123) fluorescence, a colorimetric assay, western blots, immunohistochemical staining and RT-PCR. Hypoxia inhibited mitochondria-dependent apoptosis and promoted HPASMC growth. In contrast, after puerarin (50 µM or more) intervention, cell growth was inhibited and apoptosis was observed. Puerarin-induced apoptosis in hypoxic HPASMCs was accompanied by reduced mitochondrial membrane potential, cytochrome c release from the mitochondria, caspase-9 activation, and Bcl-2 down-regulation with concurrent Bax up-regulation. Puerarin promoted apoptosis in hypoxic HPASMCs by acting on the mitochondria-dependent pathway. These results suggest a new mechanism of puerarin relevant to the management of clinical hypoxic pulmonary hypertension.
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