Yc-1-Inhibited Proliferation of Rat Mesangial Cells through Suppression of Cyclin D1—Independent of Cgmp Pathway and Partially Reversed by P38 Mapk Inhibitor
Resource
EUROPEAN JOURNAL OF PHARMACOLOGY v.517 n.1-2 pp.1-10
Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Journal Volume
v.517
Journal Issue
n.1-2
Pages
1-10
Date Issued
2005
Date
2005
Author(s)
HSIEH, BOR-SHEN
TSAI, TUN-JEN
CHEN, YUNG-MING
Abstract
This study was designed to investigate the effect of 1- benzyl-3-(5′- hydroxymethyl-2′-furyl) indazole (YC-1), a guanylate cyclase activator, upon the proliferation of rat mesangial cells and its underlying mechanism . YC-1 inhibited cell proliferation and DNA synthesis in a dose- and time- dependent manner. Flow cytometry cell-cycle studies revealed that YC-1 prevented the entry of cells from G1 into S phase . The expression of cyclin D1 and the kinase activity of cyclin D1/cyclin-dependent kinase ( CDK)4 were lower within YC-1-treated cells, revealed by Western blotting, Northern blotting and kinase assays. YC-1 did not increase the intracellular cGMP concentration in mesangial cells. Inhibitors of soluble guanylate cyclase, protein kinase G, or protein kinase A also did not reverse the inhibitory effect elicited by YC-1, while co-treatment with p 38 mitogen -activated protein kinase (MAPK) inhibitor could partially reverse the suppressive effect. YC-1 inhibited proliferation of mesangial cells and induced cell-cycle arrest by the reduction of cyclin D1 synthesis and cyclin D1/CDK4 kinase activity. This effect acts partially through p38 MAPK signal transduction activation and is independent of cGMP - signaling pathways.
Subjects
p38 mitogen-activated protein kinase
Proliferation
Cyclin D1
Mesangial cells
YC-1
Type
journal article