ナガサカ　ヤスコ   NAGASAKA Yasuko   長坂　安子    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Nitric oxide regulates pulmonary vascular smooth muscle cell expression of the inducible cAMP early repressor gene.
掲載誌名	正式名：Nitric oxide : biology and chemistry 略　 称：Nitric Oxide ISSNコード：10898611/10898603
掲載区分	国外
巻・号・頁	25(3),pp.294-302
国際共著	国際共著
著者・共著者	Steinbicker Andrea U, Liu Heling, Jiramongkolchai Kim, Malhotra Rajeev, Choe Elizabeth Y, Busch Cornelius J, Graveline Amanda R, Kao Sonya M, Nagasaka Yasuko, Ichinose Fumito, Buys Emmanuel S, Brouckaert Peter, Zapol Warren M, Bloch Kenneth D
発行年月	2011/10
概要	Nitric oxide (NO) regulates vascular smooth muscle cell (VSMC) structure and function, in part by activating soluble guanylate cyclase (sGC) to synthesize cGMP. The objective of this study was to further characterize the signaling mechanisms by which NO regulates VSMC gene expression using transcription profiling. DNA microarrays were hybridized with RNA extracted from rat pulmonary artery smooth muscle cells (RPaSMC) exposed to the NO donor compound, S-nitroso-glutathione (GSNO). Many of the genes, whose expression was induced by GSNO, contain a cAMP-response element (CRE), of which one encoded the inducible cAMP early repressor (ICER). sGC and cAMP-dependent protein kinase, but not cGMP-dependent protein kinase, were required for NO-mediated phosphorylation of CRE-binding protein (CREB) and induction of ICER gene expression. Expression of a dominant-negative CREB in RPaSMC prevented the NO-mediated induction of CRE-dependent gene transcription and ICER gene expression. Pre-treatment of RPaSMC with the intracellular calcium (Ca(2+)) chelator, BAPTA-AM, blocked the induction of ICER gene expression by GSNO. The store-operated Ca(2+) channel inhibitors, 2-ABP, and SKF-96365, reduced the GSNO-mediated increase in ICER mRNA levels, while 2-ABP did not inhibit GSNO-induced CREB phosphorylation. Our results suggest that induction of ICER gene expression by NO requires both CREB phosphorylation and Ca(2+) signaling. Transcription profiling of RPaSMC exposed to GSNO revealed important roles for sGC, PKA, CREB, and Ca(2+) in the regulation of gene expression by NO. The induction of ICER in GSNO-treated RPaSMC highlights a novel cross-talk mechanism between cGMP and cAMP signaling pathways.
DOI	10.1016/j.niox.2011.05.006
PMID	21642009