Captopril inhibits pp60(c-src) tyrosine phosphorylation in cultured human mesangial cells.
The present experiments were devoted to analyzing the mechanisms involved in the captopril-dependent inhibition of human mesangial cell proliferation. Studies were performed in cultured human mesangial cells incubated with captopril, an angiotensin II-converting enzyme inhibitor with antioxidant properties, lisinopril, a non-antioxidant angiotensin II-converting enzyme inhibitor, and tocopherol, a pure antioxidant. Both angiotensin II-converting enzyme inhibitors significantly inhibited fetal calf serum-induced [3H]thymidine uptake by human mesangial cells, in a dose- and time-dependent manner, an effect which was not observed with tocopherol. The antiproliferative effect of captopril and its ability to block tyrosine phosphorylation of human mesangial cells proteins were significantly greater than those of lisinopril. Moreover, captopril significantly prevented the fetal calf serum-induced tyrosine phosphorylation of pp60(c-src). The present results suggest that the antiproliferative ability of captopril does not completely depend on its angiotensin II-converting enzyme inhibitor properties, pointing to a possible interaction of the drug with the intracellular mechanisms responsible for the transmission of the proliferative signals.
Ruiz-Ginés
J A
JA
Department of Physiology and Pharmacology, Alcalá de Henares University, Madrid, Spain.
Pérez-Caballero
C
C
O'Valle
F
F
Rodríguez-Puyol
M
M
Rodríguez-Puyol
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017706:Lisinopril / Q000494:pharmacology; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D014810:Vitamin E; D002216:Captopril; D017706:Lisinopril; D016392:Proto-Oncogene Proteins pp60(c-src)