Cigarette smoke extract induces endothelial cell injury via JNK pathway
Cigarette smoke extract induces endothelial cell injury via JNK pathway
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DOI：
10.1016/j.bbrc.2005.01.095
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Kawase, I
中科院分区：
文献类型：
--
作者：
Hoshino, S;Yoshida, M;Kawase, I
吸烟是导致慢性阻塞性肺疾病（COPD）的最重要因素。然而，这种疾病发展的确切机制尚未完全了解。近年来，肺内皮细胞损伤越来越被认为是COPD的一个重要病理生理过程。为了验证这一假设，我们研究了香烟烟雾提取物（CSE）如何损害人脐静脉内皮细胞（HUVECs）。CSE激活了c-Jun n -末端激酶（JNK），用JNK途径的特异性抑制剂SP600125治疗HUVECs可显著抑制CSE对内皮细胞的损伤。相反，抑制细胞外调节激酶或p38通路不影响CSE的细胞毒性。此外，抗氧化剂超氧化物歧化酶和过氧化氢酶可以减少cse诱导的JNK磷酸化和内皮细胞损伤。这些结果表明，CSE通过氧化应激激活的JNK通路（至少部分激活）损害血管内皮细胞。(C) 2005爱思唯尔公司版权所有。
Cigarette smoking is the most crucial factor responsible for chronic Obstructive pulmonary disease (COPD). The precise mechanisms of the development of the disease have, however, not been fully understood. Recently, impairment of pulmonary endothelial cells has been increasingly recognized as a critical pathophysiological process in COPD. To verify this hypothesis, we examined how cigarette smoke extract (CSE) damages human umbilical vein endothelial cells (HUVECs). CSE activated c-Jun N-terminal kinase (JNK), and treatment of HUVECs with SP600125, a specific inhibitor of the JNK pathway, significantly suppressed endothelial cell damage by CSE. In contrast, inhibition of the extracellular-regulated kinase or the p38 pathway did not affect the cytotoxicity of CSE. Furthermore, anti-oxidants superoxide dismutase and catalase reduced CSE-induced JNK phosphorylation and endothelial cell injury. These results indicate that CSE damages vascular endothelial cells through the JNK pathway activated, at least partially, by oxidative stress. (C) 2005 Elsevier Inc. All rights reserved.