Cilostazol enhances IL-1β-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway

被引：18

作者：

Ito, C ^{[1
]}

Kusano, E ^{[1
]}

Akimoto, T ^{[1
]}

Takeda, S ^{[1
]}

Sasaki, N ^{[1
]}

Umino, T ^{[1
]}

Iimura, O ^{[1
]}

Ando, Y ^{[1
]}

Asano, Y ^{[1
]}

机构：

[1] Jichi Med Sch, Dept Nephrol, Minami Kawachi, Tochigi 3290498, Japan

来源：

CELLULAR SIGNALLING | 2002年 / 14卷 / 07期

关键词：

cilostazol; inducible nitric oxide synthase; vascular smooth muscle; interleukin-1; beta; apoptosis; protein kinase A;

D O I：

10.1016/S0898-6568(02)00004-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Interleukin-1beta (IL-1beta) stimulates nitric oxide (NO) production and induces apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor. We investigated whether cilostazol affects IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM-10 muM) potentiated NO production triggered by IL-1beta. The mRNA and protein expression of inducible NO synthase was also upregulated by cilostazol. KT5720, an inhibitor of protein kinase A, and N-G-monomethyl-L-arginine, an inhibitor of NO synthase, abrogated cilostazol-enhanced IL-1beta-stimulated NO production and apoptosis. These results shows that cilostazol potentiates IL-1beta-induced NO production via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway. (C) 2002 Elsevier Science Inc. All rights reserved.

引用

页码：625 / 632

页数：8

共 30 条

[11] INDUCTION OF NITRIC-OXIDE SYNTHASE IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS - THE ROLE OF CYCLIC-AMP [J].

HIROKAWA, K ;

OSHAUGHNESSY, K ;

MOORE, K ;

RAMRAKHA, P ;

WILKINS, MR .

BRITISH JOURNAL OF PHARMACOLOGY, 1994, 112 (02) :396-402

[12] Dipyridamole enhances interleukin-1 beta-stimulated nitric oxide production by cultured rat vascular smooth muscle cells [J].

Iimura, O ;

Kusano, E ;

Amemiya, M ;

Muto, S ;

Ikeda, U ;

Shimada, K ;

Asano, Y .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 296 (03) :319-326

[13] Effect of cilostazol, a cAMP phosphodiesterase inhibitor, on nitric oxide production by vascular smooth muscle cells [J].

Ikeda, U ;

Ikeda, M ;

Kano, S ;

Kanbe, T ;

Shimada, K .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 314 (1-2) :197-202

[14] INDUCTION OF NITRIC-OXIDE SYNTHASE BY CYCLIC-AMP IN RAT VASCULAR SMOOTH-MUSCLE CELLS [J].

IMAI, T ;

HIRATA, Y ;

KANNO, K ;

MARUMO, F .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) :543-549

[15] APOPTOSIS IN HUMAN ATHEROSCLEROSIS AND RESTENOSIS [J].

ISNER, JM ;

KEARNEY, M ;

BORTMAN, S ;

PASSERI, J .

CIRCULATION, 1995, 91 (11) :2703-2711

[16] Distribution of cell replication and apoptosis in atherosclerotic plaques of cholesterol-fed rabbits [J].

Kockx, MM ;

DeMeyer, GRY ;

Muhring, J ;

Bult, H ;

Bultinck, J ;

Herman, AG .

ATHEROSCLEROSIS, 1996, 120 (1-2) :115-124

[17]

KOIDE M, 1993, J BIOL CHEM, V268, P24959

[18] 2 DISTINCT SIGNALING PATHWAYS TRIGGER THE EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN RAT RENAL MESANGIAL CELLS [J].

KUNZ, D ;

MUHL, H ;

WALKER, G ;

PFEILSCHIFTER, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (12) :5387-5391

[19] Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate production via the V-1 receptor in cultured rat vascular smooth muscle cells [J].

Kusano, E ;

Tian, S ;

Umino, T ;

Tetsuka, T ;

Ando, Y ;

Asano, Y .

JOURNAL OF HYPERTENSION, 1997, 15 (06) :627-632

[20]

LIBBY P, 1992, NOUV REV FR HEMATOL, V34, pS47

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