Acute hypoxia to endothelial cells induces activating transcription factor 3 (ATF3) expression that is mediated via nitric oxide
Acute hypoxia to endothelial cells induces activating transcription factor 3 (ATF3) expression that is mediated via nitric oxide
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DOI：
10.1016/j.atherosclerosis.2008.02.014
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发表时间：
2008-12-01
期刊：
影响因子：
5.3
通讯作者：
Wang, Danny Ling
中科院分区：
文献类型：
--
作者：
Chen, Shih-Chung;Liu, Yu-Chi;Wang, Danny Ling
内皮细胞（EC）在缺氧引起的血管疾病中发挥着重要作用。我们研究了激活转录因子 3 (ATF3) 的急性缺氧电子内皮表达，ATF3 是一种应激诱导转录因子，在细胞对应激的反应中发挥着重要作用。牛主动脉内皮细胞受到急性缺氧（1％O-2，pO（2）= 8 mmHg）并检查ATF3表达。暴露于缺氧的 ECs 短暂诱导 ATF3 表达。然而，观察到 EC 中 C-Jun-NH2 末端激酶 (JNK) 和 p38 丝裂原激活蛋白激酶 (MAPK) 的激活短暂增加。只有用 JNK 特异性抑制剂预处理的 EC 才能抑制缺氧诱导的 ATF3 表达。暴露于急性缺氧的内皮细胞会短暂增加内皮一氧化氮（eNOS）活性。用 eNOS (L-NAME) 或 PI3 激酶的 I 特异性抑制剂预处理 EC，可显着抑制缺氧诱导的 JNK 激活和 ATF3 表达。 ATF3 诱导已被证明可以抑制基质金属蛋白酶-2) (MMP-2) 的表达。一致地，暴露于缺氧的 EC 会减弱 MMP-2 的表达。这种缺氧减弱的 MMP-2 表达可以通过用 eNOS 抑制剂预处理 EC 来挽救。这些结果表明，急性缺氧诱导的 ATF3 是由 EC 中的一氧化氮和 JNK 通路介导的。我们的研究结果为内皮细胞响应急性缺氧的机制提供了分子基础。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Endothelial cells (ECs) play an important role in hypoxia-induced vascular disorders. We investigated the acute hypoxia electron endothelial expression of activating transcription factor 3 (ATF3), a stress-inducible transcription factor playing significant roles in cellular responses to stress. Bovine aortic ECs were subjected to acute hypoxia (1%O-2, pO(2) = 8 mmHg) and ATF3 expression was examined. ECs exposed to hypoxia transiently induced ATF3 expression. A transient increase in the activation of C-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in ECs was observed: however. only ECs pretreated with a specific inhibitor to JNK Suppressed the hypoxia-induced ATF3 expression. ECs exposed to acute hypoxia transiently increased endothelial nitric oxide (eNOS) activity. Pre-treating ECs with,I specific inhibitor to eNOS (L-NAME) or PI3-kinase significantly inhibited the hypoxia-induced JNK activation and ATF3 expression. ATF3 induction has been shown to inhibit matrix metalloproteinase-2) (MMP-2) expression. Consistently, ECs exposed to hypoxia attenuated the MMP-2 expression. This hypoxia-attenuated MMP-2 expression can be rescued by pre-treating ECs with an inhibitor of eNOS. These results suggest that the ATF3 induction by acute hypoxia is mediated by nitric oxide and the JNK pathway in ECs. Our findings provide a Molecular basis for the mechanism in which ECs respond to acute hypoxia. (C) 2008 Elsevier Ireland Ltd. All rights reserved.