NADPH oxidase is involved in prostaglandin F2α-induced hypertrophy of vascular smooth muscle cells -: Induction of NOX1 by PGF2α
NADPH oxidase is involved in prostaglandin F2α-induced hypertrophy of vascular smooth muscle cells -: Induction of NOX1 by PGF2α
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DOI：
10.1074/jbc.m111634200
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发表时间：
2002-04-19
影响因子：
4.8
通讯作者：
Yabe-Nishimura, C
中科院分区：
文献类型：
--
作者：
Katsuyama, M;Fan, CY;Yabe-Nishimura, C
前列腺素(PG)F-2α是血管组织中产生的一种主要前列腺素，可导致血管平滑肌细胞肥大。为了阐明前列腺素F(2α)诱导的肥大的分子机制，我们在大鼠血管平滑肌细胞系A7r5中检测了活性氧的参与。前列腺素F受体的选择性激动剂PGF(2α)和(+)-氟前列烯醇显著增加A7r5细胞内O-2(-)。PGF(2pha)诱导的O-2(-)升高可被NADPH氧化酶的抑制剂二苯基碘(DPI)所抑制，DPI被认为是血管细胞内O2的主要来源。在DPI存在下，PGF(2α)或(+)-氟前列烯醇诱导的蛋白质合成增强被抑制。Northern印迹分析显示，在PGF(2α)或(+)-氟前列烯醇处理的细胞中，吞噬细胞NADPH氧化酶gp91催化亚基的同源物NOX1的表达呈剂量依赖性增加。最后，在针对mRNA序列上三个独立切割位点的核酶转染的细胞中，NOX1 mRNA的缺失显著降低了PGF(2pha)诱导的蛋白质合成的增加。综上所述，上述结果提示PGF(2α)引起的血管平滑肌细胞肥大是通过NOX1诱导和NADPH氧化酶产生O-2(-)介导的。
Prostaglandin (PG) F-2alpha, one of the primary prostanoids generated in vascular tissue, is known to cause hypertrophy in vascular smooth muscle cells. To clarify the molecular mechanisms underlying PGF(2alpha)-induced hypertrophy, the involvement of reactive oxygen species was examined in a rat vascular smooth muscle cell line, A7r5. PGF(2alpha) and (+)-fluprostenol, a selective agonist of the PGF receptor, significantly increased intracellular O-2(-) in A7r5. The PGF(2alpha)-induced O-2(-) increase was suppressed by diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase that has been reported to be the major source of 02 in vascular cells. The augmented synthesis of the protein induced by PGF(2alpha) or (+)-fluprostenol was suppressed in the presence of DPI. In PGF(2alpha) or (+)-fluprostenol-treated cells, a dose-dependent increase in the expression of NOX1, a homolog of the catalytic subunit of the phagocyte NADPH oxidase gp91(phox), was demonstrated by Northern blot analysis. Finally, depletion of NOX1 mRNA in the cells transfected with ribozymes targeted for three independent cleavage sites on the mRNA sequence significantly reduced the PGF(2alpha)-induced increase in protein synthesis. Taken together, these results suggest that hypertrophy of vascular smooth muscle cells caused by PGF(2alpha) is mediated by NOX1 induction and the resultant overproduetion of O-2(-) by NADPH oxidase.