期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 43, 期 6, 页码 976-986出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2007.06.001
关键词
NADPH oxidase; endothelial cells; cell cycle; p21(cip1); p53; apoptosis; ROS
资金
- Biotechnology and Biological Sciences Research Council [BB/D009510/1] Funding Source: Medline
- Wellcome Trust [078637/z/05/z, 078637] Funding Source: Medline
- Wellcome Trust [078637/Z/05/Z] Funding Source: Wellcome Trust
- BBSRC [BB/D009510/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D009510/1] Funding Source: researchfish
Endothelial cells (EC) express constitutively two major isofonns (Nox2 and Nox4) of the catalytic subunit of NADPH oxidase, which is a major source of endothelial reactive oxygen species. However, the individual roles of these Noxes in endothelial function remain unclear. We have investigated the role of Nox2 in nutrient deprivation-induced cell cycle arrest and apoptosis. In proliferating human dermal microvascular EC, Nox2 mRNA expression was low relative to Nox4 (Nox2:Nox4 similar to 1:13), but was upregulated 24 It after starvation and increased to 8 +/- 3.5-fold at 36 h of starvation. Accompanying the upregulation of Nox2, there was a 2.28 +/- 0.18-fold increase in O-2(-); production, a dramatic induction of p21(cip1) and p53, cell cycle arrest, and the onset of apoptosis (all p < 0.05). All these changes were inhibited significantly by in vitro deletion of Nox2 expression and in coronary microvascular EC isolated from Nox2 knockout mice. In Nox2 knockout cells, although there was a 3.8 +/- 0.5fold increase in Nox4 mRNA expression after 36 h of starvation (p < 0.01), neither production nor the p21(cip1) or p53 expression was increased significantly and only 0.46% of cells were apoptotic. In conclusion, Nox2-derived O-2(-), through the modulation of p21(cip1) and p53 expression, participates in endothelial cell cycle regulation and apoptosis. (c) 2007 Elsevier Inc. All rights reserved.
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