Nitric oxide inhibits growth of glomerular mesangial cells: Role of the transcription factor EGR-1

作者: Harald D. Rupprecht , Yoshitaka Akagi , Annette Keil , Gerhard Hofer

DOI: 10.1046/J.1523-1755.2000.00828.X

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摘要: Nitric oxide inhibits growth of glomerular mesangial cells: Role the transcription factor Egr-1 Background In previous studies, we found a close link early response gene-1 (Egr-1) expression to cell (MC) proliferation. Antiproliferative agents inhibited mitogen-induced expression. Here investigated effect S-nitrosoglutathione (GSNO) on proliferation MCs, specifically asking how GSNO regulates Egr-1, which have previously shown be critical for induction MC mitogenesis. Methods The MCs was measured by thymidine incorporation and counting. mRNA protein levels were detected Northern Western blots. Electrophoretic mobility shift assays (EMSAs) chloramphenicol acetyltransferase (CAT) performed test whether modulates DNA binding transcriptional activation Egr-1. Results strongly serum-induced (-84% at 1 mmol/L). A mild inhibition observed concentrations from 50 200 μmol/L, whereas increased again above 500 μmol/L. This expression, however, not translated into protein. Instead, (-40%). EMSAs indicated that specific its consensus sequence. Moreover, in CAT using reporter plasmid bearing three sites suppressed GSNO. Conclusions Our data identify as potent inhibitor with potential beneficial effects proliferative diseases. antimitogenic property is mediated least part inhibitory reducing ability activate impairing activity.

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