Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells
Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells
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DOI：
10.1016/j.lfs.2004.11.015
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发表时间：
2005-04-29
期刊：
影响因子：
6.1
通讯作者：
Yamori, Y
中科院分区：
文献类型：
--
作者：
Xu, JW;Ikeda, K;Yamori, Y
咖啡酸是一种从咖啡、水果和蔬菜中提取的膳食苯酚，是一种有效的抗氧化剂。然而，对其在调节基本细胞过程中的抗氧化机制知之甚少。在这项研究中，我们研究了咖啡酸是否调节NADPH氧化酶的合作伙伴rac1 GTP酶的活性。我们的结果表明，咖啡酸在基础条件下和与血管紧张素II(Ang II)孵育时，会降低血管平滑肌细胞中rac1的蛋白水平。在RAC与PAK结合的下拉实验中，咖啡酸明显抑制了rac1的活性。我们还观察到咖啡酸抑制了Ang II刺激的超氧阴离子的产生，Ang II激活了NADPH氧化酶。另一方面，与Caffei CAID和放线菌亚胺共孵育显著加速了rac1的降解。此外，当Ang II通过氧化还原敏感途径攻击细胞时，咖啡酸预处理24小时可阻止MLC和HSP27的磷酸化。这些结果支持这样的假设，即咖啡酸降低了rac1 GTPase的蛋白和活性水平，随后下调了NADPH氧化酶的活性。(C)2005 Elsevier Inc.保留所有权利。
Caffeic acid, a dietary phenol from coffee, fruits and vegetables, is an efficient antioxidant. However, little is known about its anti-oxidative mechanism in the modulation of fundamental cellular processes. In this study, we investigated whether caffeic acid regulates Rac1 GTPase activity, a partner of NADPH oxidase. Our results showed that caffeic acid decrease Rac1 protein level under basal conditions and incubation with angiotensin II (ANG II) in vascular smooth muscle cells. In a Rac-bound-to-PAK pull down assay, caffeic acid clearly inhibited Rac1 activity. We also observed that caffeic acid suppressed the generation of superoxide anion stimulated by ANG II that activates NADPH oxidase. On the other hand, co-incubation with caffei caid and cycloheximide significantly accelerated the Rac1 degradation. In addition, pretreatment with caffeic acid for 24 hours was able to prevent phosphorylation of MLC and HSP27, when cells were challenged with ANG II through the redox sensitive pathway. These results support the hypothesis that caffeic acid reduces Rac1 GTPase protein and activity level, followed by a down-regulation of NADPH oxidase activity. (c) 2005 Elsevier Inc. All rights reserved.