Captopril-dependent inhibition of collagen biosynthesis in cultured fibroblasts.
The mechanism underlying the dermatological manifestations that accompany captopril therapy is not known. The facts that prolidase plays an important role in collagen biosynthesis and that captopril directly inhibits prolidase activity led us to evaluate its effect on collagen biosynthesis in cultured human skin fibroblasts. Confluent fibroblasts were treated with milimolar concentrations (0.2-1 mM) of captopril (CAP) for 48 h. It was found that CAP-dependent decrease in prolidase activity was accompanied by parallel decrease in collagen biosynthesis. Since insulin-like growth factor receptor (IGF-IR) is the most potent regulator of both collagen biosynthesis and prolidase activity, and prolidase is regulated by beta1 integrin signaling, the effect of CAP on IGF-IR and beta1 integrin receptor expressions was evaluated. It was found that exposure of the cells to 0.3 mM CAP contributed to a decrease in IGF-IR, alpha2beta1 integrin receptor and MAPK/ERK1/2 expressions. The data suggest that CAP-dependent decrease of collagen biosynthesis in cultured human skin fibroblasts results from inhibition of prolidase activity that may occur through inhibition of alpha2beta1 integrin and IGF-IR signaling.
Karna
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Department of Medicinal Chemistry, Medical University in Bialystok, Poland.
Szoka
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Palka
J A
JA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology*; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D004150:Dipeptidases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011392:Proline / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000096:biosynthesis; D012867:Skin / Q000166:cytology
D000806:Angiotensin-Converting Enzyme Inhibitors; D017451:Receptors, Somatomedin; D003094:Collagen; D011392:Proline; D002216:Captopril; D004150:Dipeptidases; C022449:proline dipeptidase