Collagen prolyl hydroxylation in WI-38 fibroblast cultures: action of hydralazine.
The action of hydralazine on collagen prolyl hydroxylation was studied in a cell culture system using WI-38 fibroblasts. The prolyl hydroxylation level was determined by a method involving the digestion of collagen by bacterial collagenase and the examination of specific peptides. The presence of low concentrations of hydralazine (0.2 mM) in both "young" and "old" fibroblast cultures strongly inhibited collagen prolyl hydroxylation. The degree of inhibition was greater in serum-deficient cultures. No significant improvement in the degree of hydroxylation was observed by increasing either ascorbate or iron levels in the hydralazine-containing cultures in which hydroxylation was inhibited. Some of the reported side effects of hydralazine seen in patients might be related to its inhibitory effects on mixed function oxidative (MFO) hydroxylation systems. While the ascorbate dependence of the prolyl hydroxylase system of WI-38 decreased with the "age" of the culture, hydralazine inhibition of hydroxylation was dramatic with cultures of all "ages".
D001205:Ascorbic Acid / Q000494:pharmacology; D001769:Blood; D002460:Cell Line; D002470:Cell Survival; D003094:Collagen / Q000378:metabolism*; D003470:Culture Media; D006830:Hydralazine / Q000494:pharmacology*; D006900:Hydroxylation; D007501:Iron / Q000494:pharmacology; D011392:Proline / Q000378:metabolism*
D003470:Culture Media; D006830:Hydralazine; D003094:Collagen; D011392:Proline; D007501:Iron; D001205:Ascorbic Acid