20-Hydroxyeicosatetraenoic acid inhibits the apoptotic responses in pulmonary artery smooth muscle cells
20-Hydroxyeicosatetraenoic acid inhibits the apoptotic responses in pulmonary artery smooth muscle cells
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DOI：
10.1016/j.ejphar.2008.03.045
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发表时间：
2008-06-24
影响因子：
5
通讯作者：
Zhu, Daling
中科院分区：
文献类型：
--
作者：
Wang, Zhigang;Tang, Xiaobo;Zhu, Daling
20-羟基二十碳四烯酸(20-HETE)是细胞色素P450-4A(CyP4A)催化花生四烯酸的omega-羟基化产物，在血管平滑肌重塑中起重要作用。尽管20-HETE对血管生成反应的影响是已知的，但20-HETE是否对PASMC重塑的重要步骤--PASMC的凋亡起作用，以及参与该过程的途径尚不清楚。在这里，我们展示了丢失信息的证据。通过细胞存活率、Annexin V与碘化丙啶结合、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)、线粒体电位测定、半胱氨酸天冬氨酸氨基转移酶(Caspase)活性测定和Western blotting检测20-HETE对PASMC凋亡及其相关信号通路的影响。我们发现外源20-HETE可抑制血清剥夺所致的牛PASMCs丢失，并阻止Annexin V结合、DNA缺口末端标记和染色质凝聚。17-十八烷基环酸(17-ODYA)可抑制内源性20-HETE的产生，从而加重这种作用。此外，20-HETE可诱导bcl2的表达，维持线粒体膜的稳定性，并缓解caspase-9和caspase-3的激活。在17-ODYA存在下，这种作用被逆转。因此，这些发现表明，20-HETE至少部分地作用于固有的凋亡途径，从而保护PASMC免受凋亡的影响。(C)2008爱思唯尔B.V.保留所有权利。
20-Hydroxyeicosatetraenoic acid (20-HETE), a omega-hydroxylation product of arachidonic acid catalyzed by cytochrome P450 4A (CYP4A), plays a role in vascular smooth muscle remodeling. Although its effects on angiogenic responses are known, it remains unclear whether 20-HETE acts on apoptosis of pulmonary arterial smooth muscle cells (PASMC), an important step in PASMC remodeling, and what pathways are involved in the process. Here we show evidence for the missing information. The effect of 20-HETE on PASMC apoptosis and the apoptosis-associated signaling pathways were determined with cell viability assay, Annexin V and propidium idodide binding, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), mitochondrial potentials assay, caspase activity assay and Western blots. We found that exogenous 20-HETE suppressed the serum deprivation-induced loss of bovine PASMCs and prevented Annexin V binding, DNA nick end labeling and chromatin condensation. The effect was worsened by 17-octadecynoic acid (17-ODYA), which inhibited the production of endogenous 20-HETE. Furthermore, 20-HETE induced the expression of bcl-2, maintained the stability of mitochondria membrane, and relieved the activation of caspase-9 and caspase-3. Such effects were reversed in the presence of 17-ODYA. Thus, these findings indicate that 20-HETE protects PASMCs against apoptosis by acting on, at least in part, the intrinsic apoptotic pathway. (C) 2008 Elsevier B.V. All rights reserved.