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IR@PKUHSC  > 北京大学第二临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Regulation of intracellular Ca2(+) and calcineurin by NO/PKG in proliferation of vascular smooth muscle cells
作者: Li, SJ; Sun, NL
关键词: cacium ; calcineurin ; nitric oxide ; cGMP-dependent protein kinase ; vascular smooth muscle
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2005-03-01
DOI: 10.1111/j.1745-7245.2005.00049.x
卷: 26, 期:3, 页:323-328
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: DEPENDENT PROTEIN-KINASE ; CA2+ SENSITIZATION ; CARDIAC MYOCYTES ; NITRIC-OXIDE ; TRANSCRIPTION ; INHIBITION ; ACTIVATION ; MECHANISMS
英文摘要:

Aim: To determine whether Ca2+/calcineurin mediated the inhibitory effects of nitric oxide /cGMP-dependent protein kinase (NO/PKG) on the proliferation of vascular smooth muscle cells (VSMC). Methods: Proliferation and viability of primary VSMC from rat aorta were measured using [3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] (MTT) assay and acridine orange and ethidium bromide staining, respectively. Cytosolic Ca2+ was determined by Fluo-3/AM. Calcineurin protein and its activity were assayed using immunoblotting and free inorganic phosphate analysis, respectively. Results: (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) and Sp-8-(4-chlorophenylthio)-guanosine-3′,5′-cyclic monophosphorothioate (Sp-8-pCPT-cGMPS) decreased phenylephrine (PE)-induced proliferation of VSMC by 27.3% and 36.6%, respectively, but Rp-8-[4-chlorophenyl)thio]-guanosine-3′,5′-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS) increased PE-induced proliferation of VSMC. SNAP, Sp-8-pCPT-cGMPS, and Rp-8-pCPT-cGMPS did not affect the viability of VSMC. Calcineurin protein was decreased by 63.1% and its activity was decreased by 59.7% in smooth muscle cells (SMC) pretreated with verapamil (Ver) and then stimulated by PE. In SMC pretreated with Ver, the absorbance of cells stimulated by PE decreased by 22.0% and was further inhibited by the additional treatment of SNAP and Sp-8-pCPT-cGMPS. In SMC pretreated with cyclosporin A (CsA), the absorbance of cells stimulated by PE decreased by 36.7%, but could not be further altered by the additional treatment of SNAP, Sp-8-pCPT-cGMPS, and Rp-8-pCPT-cGMPS. In addition, Ver inhibited PE-induced intracellular Ca 2, variations, which could be further inhibited by SNAP and Sp-8-pCPT-cGMPS, but not by Rp-8-pCPT-cGMPS. Moreover, the increase in calcineurin activity induced by PE was inhibited by SNAP and Sp-8-pCPT-cGMPS, but was promoted by Rp-8-pCPT-cGMPS. Conclusion: NO/PKG regulates calcineurin activity via the modulation of intracellular Ca 2, concentration, and thus partially inhibits the proliferation of VSMC without affecting their viability.

语种: 英语
WOS记录号: WOS:000227647800010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62907
Appears in Collections:北京大学第二临床医学院_心血管内科_期刊论文

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作者单位: Peking Univ, Dept Cardiol, Peoples Hosp, Beijing 100044, Peoples R China

Recommended Citation:
Li, SJ,Sun, NL. Regulation of intracellular Ca2(+) and calcineurin by NO/PKG in proliferation of vascular smooth muscle cells[J]. ACTA PHARMACOLOGICA SINICA,2005,26(3):323-328.
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