Basal nitric oxide release attenuates cell migration of HeLa and endothelial cells

被引：19

作者：

Bulotta, Stefania ^{[2
]}

Ierardi, Maria Vincenza ^{[2
]}

Maiuolo, Jessica ^{[2
]}

Cattaneo, Maria Grazia ^{[3
]}

Cerullo, Andrea ^{[2
]}

Vicentini, Lucia M. ^{[3
]}

Borgese, Nica ^{[1
,2
,3
]}

机构：

[1] CNR, Inst Neurosci, I-20129 Milan, Italy

[2] Univ Catanzaro Magna Graecia, Dept Pharmacobiol Sci, Catanzaro, Italy

[3] Univ Milan, Dept Med Pharmacol, Milan, Italy

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 386卷 / 04期

关键词：

Akt; Boyden chambers; Chemotaxis; cGMP; Endothelial NO synthase; HeLa TetOff cells; Human Umbilical Vein Endothelial Cells; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR; KINASE AKT; SYNTHASE; ANGIOGENESIS; ACTIVATION; PATHWAY; PHOSPHORYLATION; DOWNSTREAM; DEATH;

D O I：

10.1016/j.bbrc.2009.06.118

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nitric oxide (NO) generated by endothelial NO synthase (eNOS) is a key regulator of endothelial cell (EC) migration. Whereas the effects of acute NO generation are generally stimulatory, the role of chronic basal NO release has not been explored so far. Here, we addressed this question both in HeLa and in human endothelial cells. In stably transfected HeLa cells, inducibly expressing eNOS, expression of the enzyme per se blunted the phosphorylation of Akt/PKB in response to serum and strongly inhibited chemotaxis, an effect partially blocked by eNOS- and Soluble guanylyl cyclase (sGC) inhibitors. Likewise, long-term pre-treatment of non-transfected HeLa cells with nanomolar concentrations of an NO donor inhibited subsequent migration, an effect blocked by sGC inhibition and mimicked by a cGMP analog. Finally, EC migration was stimulated by chronic pre-treatment with an eNOS inhibitor. Thus, in addition to its well-known stimulatory role, eNOS attenuates migration through basal long-term NO release. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：744 / 749

页数：6

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