Rac-Dependent Monocyte Chemoattractant Protein-1 Production Is Induced by Nutrient Deprivation
作者:
Neuza Lopes,
Sanjay Vasudevan,
David Gregg,
Balakrishnan Selvakumar,
Patrick Pagano,
Herve Kovacic,
Pascal Goldschmidt-Clermont,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 91,
issue 9
页码: 798-805
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: monocyte chemoattractant protein-1;superoxide;Rac;nutrient deprivation;ischemia
数据来源: OVID
摘要:
Abstract—Under ischemic conditions, the vessel wall recruits inflammatory cells. Human aortic endothelial cells (HAECs) exposed to hypoxia followed by reoxygenation produce monocyte chemoattractant protein-1 (MCP-1); however, most experiments have been performed in the presence of nutrient deprivation (ND). We hypothesized that ND rather than hypoxia mediates endothelial MCP-1 production during ischemia, and that the small GTP-binding protein Rac1 and reactive oxygen species (ROS) are involved in this process. ND was generated by shifting HAECs from 10% to 1% FBS. Superoxide production by HAECs was increased 6 to 24 hours after ND, peaking at 18 hours. MCP-1 production was increased over a similar time frame, but peaked later at 24 hours. These effects were blocked by treatment with antioxidants such as superoxide dismutase mimetic andN-acetylcysteine (NAC), or NADPH oxidase inhibitors, DPI and gp91ds-tat. Superoxide and MCP-1 production were enhanced by RacV12 (constitutively active) in the absence of ND, and were inhibited by RacN17 (dominant-negative) adenoviral transduction under ND, suggesting that the small G-protein Rac1 is required. In conclusion, ND, an important component of ischemia, is sufficient to induce MCP-1 production by HAECs, and such production requires a functional Rac1, redox-dependent pathway.
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