Contribution of protein kinase C to ET-1-induced proliferation in human myometrial cells

被引：16

作者：

Tertrin-Clary, C ^{[1
]}

Eude, I ^{[1
]}

Fournier, T ^{[1
]}

Paris, B ^{[1
]}

Breuiller-Fouché, M ^{[1
]}

Ferré, F ^{[1
]}

机构：

[1] Univ Paris 05, INSERM U361, F-75014 Paris, France

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1999年 / 276卷 / 03期

关键词：

endothelin; myometrium;

D O I：

10.1152/ajpendo.1999.276.3.E503

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The role of protein kinase C (PKC) in endothelin-1 (ET-l)-induced proliferation of human myometrial cells was investigated. ET-1 dose dependently stimulated DNA synthesis and the number of cultured myometrial cells. Inhibition of PKC by calphostin C or Ro-31-8220 or downregulation of PKC eliminated the proliferative effects of ET-I. The failure of two protein tyrosine kinase (PTK) inhibitors (tyrphostin 51 and tyrphostin 23) to affect ET-l-induced proliferation supports the hypothesis of noninvolvement-of the tyrosine kinase signaling pathway in this process. The expression and distribution of PKC isoforms were examined by Western blot analysis. The five PKC isoforms (PKC-alpha, -beta(1), -beta(2), -zeta; -epsilon) evidenced in human myometrial tissue were found to be differentially expressed in myometrial cells, with a predominant expression of PKC-alpha and PKC-zeta. Treatment with phorbol 12,13-dibutyrate (PDBu) resulted in the translocation of all five isoforms to the particulate fraction, whereas ET-1 induced a selective increase in particulate PKC-beta(1), PKC-beta(2), and PKC-epsilon. Our findings that multiple PKC isoforms are differentially responsive to ET-1 or PDBu suggest that they play distinct roles in the myometrial growth process.

引用

页码：E503 / E511

页数：9

共 42 条

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