Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion

被引:122
作者
Lee, SL [1 ]
Wang, WW [1 ]
Finlay, GA [1 ]
Fanburg, BL [1 ]
机构
[1] Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care,Dept Med,Tupper Res Inst, Boston, MA 02111 USA
关键词
signal transduction; mitogen-activated protein kinase; superoxide; smooth muscle cell; fibroblast;
D O I
10.1152/ajplung.1999.277.2.L282
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Our previous studies have shown that, through an active transport process, serotonin (5-HT) rapidly elevates O-2(-.) formation, stimulates protein phosphorylation, and enhances proliferation of bovine pulmonary artery smooth muscle cells (SMCs). We presently show that 1 mu M 5-HT also rapidly elevates phosphorylation and activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and the enhanced phosphorylation is blocked by the antioxidants Tiron, N-acetyl-L-cysteine (NAC), and Ginkgo biloba extract. inhibition of MAP kinase with PD-98059 failed to block enhanced O-2(-.) formation by 5-HT. Chinese hamster lung fibroblasts (CCL-39 cells), which demonstrate both 5-HT transporter and receptor activity, showed a similar response to 5-HT (i.e., enhanced mitogenesis, O-2(-.) formation, and ERK1 and ERK2 phosphorylation and activation). Unlike SMCs,they also responded to 5-HT receptor agonists. We conclude that downstream signaling of MAP kinase is a generalized cellular response to 5-HT that occurs secondary to O-2(-.) formation and may be initiated by either the 5-HT transporter or receptor depending on the cell type.
引用
收藏
页码:L282 / L291
页数:10
相关论文
共 47 条
[31]   SEROTONIN UPTAKE AND CONFIGURATIONAL CHANGE OF BOVINE PULMONARY-ARTERY SMOOTH-MUSCLE CELLS IN CULTURE [J].
LEE, SL ;
DUNN, J ;
YU, FS ;
FANBURG, BL .
JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 138 (01) :145-153
[32]   SEROTONIN UPTAKE BY BOVINE PULMONARY-ARTERY ENDOTHELIAL-CELLS IN CULTURE .1. CHARACTERIZATION [J].
LEE, SL ;
FANBURG, BL .
AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 250 (05) :C761-C765
[33]  
LEE SL, 1991, J PHARMACOL EXP THER, V257, P895
[34]   MODULATION OF FIBROBLAST PROLIFERATION BY OXYGEN FREE-RADICALS [J].
MURRELL, GAC ;
FRANCIS, MJO ;
BROMLEY, L .
BIOCHEMICAL JOURNAL, 1990, 265 (03) :659-665
[35]  
NASHIO E, 1997, BIOCHEM BIOPH RES CO, V232, P1
[36]   Cell biology - Superoxides relay Ras protein's oncogenic message [J].
Pennisi, E .
SCIENCE, 1997, 275 (5306) :1567-1568
[37]   ACTIVE OXYGEN SPECIES STIMULATE VASCULAR SMOOTH-MUSCLE CELL-GROWTH AND PROTOONCOGENE EXPRESSION [J].
RAO, GN ;
BERK, BC .
CIRCULATION RESEARCH, 1992, 70 (03) :593-599
[38]   PLATELET-DERIVED GROWTH-FACTOR STIMULATES FORMATION OF ACTIVE P21RAS.GTP COMPLEX IN SWISS MOUSE 3T3-CELLS [J].
SATOH, T ;
ENDO, M ;
NAKAFUKU, M ;
NAKAMURA, S ;
KAZIRO, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (15) :5993-5997
[39]   SEROTONIN STIMULATES DNA-SYNTHESIS IN FIBROBLASTS ACTING THROUGH 5-HT 1B RECEPTORS COUPLED TO A GI-PROTEIN [J].
SEUWEN, K ;
MAGNALDO, I ;
POUYSSEGUR, J .
NATURE, 1988, 335 (6187) :254-256
[40]   SEROTONIN AS A GROWTH-FACTOR [J].
SEUWEN, K ;
POUYSSEGUR, J .
BIOCHEMICAL PHARMACOLOGY, 1990, 39 (06) :985-990