- 作者: Chuen-Mao Yang Chin-Sung Chien Yuun-Hwa Ma Li-Der Hsiao Ching-Hsuan Lin Chou-Bing Wu
- 作者服務機構: Department of Physiology/Pharmacology, Graduate Institule of Natural Products, and Department of Dentistry, Chang Gung University, Kweishan, Taoyuan, Taiwan, ROC
- 中文摘要: --
- 英文摘要:
It has been suggested that bradykini (BK) plays an
important role in regulating neointimal formation after
vascular injury. However, implication of BK in the growth
of rat vascular smooth muscle cells (VSMCs) is contro-
versial. Therefore, we examined the mitogenic effect of
BK on VSMCs associated with activation of mitogen-acti-
vated protein kinase (MAPK). Both [3H]thymidine incor-
poration and p42/p44 MAPK phosphorylation were acti-
vated by bK in time-and concentration-dependent man-
ners. Pretreatment of these cells with neither pertussis
toxin nor cholear toxin attenuated the BK-induced re-
sponses. Pretreatment of VSMCs with Hoe 140 (a se-
lective B2 receptor antagonist), U73122 (an inhibitor of
phospholipase C), and BAPTA/AM (an intracellular Ca2+
chelator) inhibited both [3H]thymidine incorporation and
p42/p44 MAPK phosphorylation in response to BK. BK-
induced [3H]thymidine incorporation and p42/p44 MAPK
phosphorylation were inhibited by pretreatent of
VSMCs with tyrosine kinase inhibitors (genistein and
herbinycin A), protein kinase C (PKC) inhibitors (stauro-
sporine, Go-6976, and Ro-318220), and MAPK kinase in-
hibitor (PD98059), and a p38 MAPK inhibitor (SB203580).
Overexpression of the dominant negative mutants, H-
Ras-15A and Raf-N4, suppressed p42/p44 MAPK activa-
tion induced by BK and PDGF-BB, indication that Ras and
Raf may be required for activation of these kinases. From
these results, we concluded that the mitogenic effect of
BK is mediated through activation of the Ras/Raf/MEK/
MAPK pathway sinilar to that of PDGF-BB, BK-mediated
MAPK activation was modulated by Ca2+, PKC, and tyro-
sine kinase all of which are associated with cell prolifera-
tion in rat cultured VSMCs. - 中文關鍵字: --
- 英文關鍵字: Cell proliferation. Mitogen-activated protein kinase. MEK. Tyrosine kinase. Protein kinase C. Vascular smooth muscle cell