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Thrombin signal transduction mechanisms in human glomerular epithelial cells

✍ Scribed by Ci-Jiang He; M. N. Peraldi; C. Adida; J. M. Rebibou; Q. Meulders; J. D. Sraer; E. Rondeau

Publisher: John Wiley and Sons
Year: 1992
Tongue: English
Weight: 880 KB
Volume: 150
Category: Article
ISSN: 0021-9541
DOI: 10.1002/jcp.1041500307

No coin nor oath required. For personal study only.

✦ Synopsis

We have previously shown that a-thrombin exerted a mitogenic effect on human glomerular epithelial cells and stimulated the synthesis of urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) and of their inhibitor, plasminogen activator inhibitor 1 (PAI-I). In the present study, we investigate the signal transduction mechanisms of thrombin in these cultured cells. Thrombin induced an increase in intracellular free calcium concentrations ( [Ca2+]i) in a dose-dependent manner, a plateau being reached at 1 U/ml thrombin. A 60% inhibition of this effect was produced by 300 n M nicardipine, a dihydroperidine agent, or by 4 m M EGTA, indicating that increase in [CaL']i was due in part to extracellular Ca2+ entry through L-type voltage-sensitive calcium channels. Thrombin also induced an increase in inositol trisphosphate (IP3), suggesting that phospholipase C activation and phosphatidylinositides breakdown were stimulated. Interestingly thrombin-stimulated cell proliferation measured by 'H thymidine incorporation was inhibited by 300 n M nicardipine, and restored by addition of lop8 M iono-

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