Stretch activates jun N-terminal kinase/stress-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors

被引:103
作者
Hamada, K
Takuwa, N
Yokoyama, K
Takuwa, Y
机构
[1] Univ Tokyo, Fac Med, Dept Physiol, Bunkyo Ku, Tokyo 113, Japan
[2] Univ Tokyo, Fac Med, Dept Cardiovasc Biol, Bunkyo Ku, Tokyo 113, Japan
[3] RIKEN Tsukuba Life Sci Ctr, Ibaraki, Osaka 305, Japan
关键词
D O I
10.1074/jbc.273.11.6334
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
Mechanical strain has been implicated in phenotypic changes, including alteration of gene expression in vascular smooth muscle cells; however, the molecular basis for mechanotransduction leading to nuclear gene expression is largely unknown. We demonstrate in the present study that cyclic stretching of vascular smooth muscle cells dramatically activates Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) through an autocrine mechanism. Stretch causes time- and strength-dependent rise of the ATP concentration in media. The stretch-induced activation JNK/SAPK is attenuated by the addition of hexokinase or apyrase that scavenge ATP in media. Both the P-2 receptor antagonist and the A(1) subtype selective P-1 receptor antagonist partially inhibit stretch-induced activation of JNK/SAPK, The conditioned medium from stretched cells contains an activity to stimulate JNK/SAPK. The JNK-stimulating activity in the conditioned medium from stretched cells is attenuated by the addition of apyrase or P-1 and P-2 receptor antagonists. The addition of exog enous ATP or adenosine induces dose-dependent activation of JNK/SAPK. These results indicate that stretch activates JNK/SAPK in vascular smooth muscle cells through mechanisms involving autocrine stimulation of purinoceptors by ATP and its hydrolyzed product adenosine.
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收藏
页码:6334 / 6340
页数:7
相关论文
共 54 条
[1]   PHORBOL ESTERS STIMULATE THE PHOSPHORYLATION OF C-JUN BUT NOT V-JUN - REGULATION BY THE N-TERMINAL DELTA DOMAIN [J].
ADLER, V ;
FRANKLIN, CC ;
KRAFT, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5341-5345
[2]   THE JUN PROTO-ONCOGENE IS POSITIVELY AUTOREGULATED BY ITS PRODUCT, JUN/AP-1 [J].
ANGEL, P ;
HATTORI, K ;
SMEAL, T ;
KARIN, M .
CELL, 1988, 55 (05) :875-885
[3]   INCREASED FLOW-INDUCED ATP RELEASE FROM ISOLATED VASCULAR ENDOTHELIAL-CELLS BUT NOT SMOOTH-MUSCLE CELLS [J].
BODIN, P ;
BAILEY, D ;
BURNSTOCK, G .
BRITISH JOURNAL OF PHARMACOLOGY, 1991, 103 (01) :1203-1205
[4]   BINDING OF THE A1-SELECTIVE ADENOSINE ANTAGONIST 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE TO RAT-BRAIN MEMBRANES [J].
BRUNS, RF ;
FERGUS, JH ;
BADGER, EW ;
BRISTOL, JA ;
SANTAY, LA ;
HARTMAN, JD ;
HAYS, SJ ;
HUANG, CC .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1987, 335 (01) :59-63
[5]   P2-PURINOCEPTORS OF 2 SUBTYPES IN THE RABBIT MESENTERIC-ARTERY - REACTIVE BLUE-2 SELECTIVELY INHIBITS RESPONSES MEDIATED VIA THE P2Y-PURINOCEPTOR BUT NOT THE P2X-PURINOCEPTOR [J].
BURNSTOCK, G ;
WARLAND, JJI .
BRITISH JOURNAL OF PHARMACOLOGY, 1987, 90 (02) :383-391
[6]   A DUAL FUNCTION FOR ADENOSINE 5'-TRIPHOSPHATE IN THE REGULATION OF VASCULAR TONE - EXCITATORY COTRANSMITTER WITH NORADRENALINE FROM PERIVASCULAR NERVES AND LOCALLY RELEASED INHIBITORY INTRAVASCULAR AGENT [J].
BURNSTOCK, G ;
KENNEDY, C .
CIRCULATION RESEARCH, 1986, 58 (03) :319-330
[7]  
BURNSTOCK G, 1985, METHOD PHARMACOL, V6, P193
[8]   PARALLEL SIGNAL-PROCESSING AMONG MAMMALIAN MAPKS [J].
CANO, E ;
MAHADEVAN, LC .
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (03) :117-122
[9]   MOLECULAR-CLONING AND FUNCTIONAL-ANALYSIS OF A NOVEL P-2 NUCLEOTIDE RECEPTOR [J].
CHANG, KG ;
HANAOKA, K ;
KUMADA, M ;
TAKUWA, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (44) :26152-26158
[10]   PPADS and suramin as antagonists at cloned P-2Y- and P-2U-purinoceptors [J].
Charlton, SJ ;
Brown, CA ;
Weisman, GA ;
Turner, JT ;
Erb, L ;
Boarder, MR .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 118 (03) :704-710