Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation.

Recently, we have described the ability of traditional lipid peroxidation inhibitors to inhibit ascorbate-stimulated collagen synthesis. In order to characterize further this effect, we have tested the ability of known and potential inhibitors of lipid peroxidation for their effects on ascorbate-stimulated collagen synthesis and lipid peroxidation. In our experiments, mannitol, a water soluble antioxidant, had no effect on ascorbate-induced collagen synthesis nor on lipid peroxidation. However, alpha-tocopherol, which is a lipophilic antioxidant, inhibited both effects of ascorbate. Superoxide dismutase, catalase, and their polyethylene glycol conjugate forms did not inhibit the ascorbate-stimulated collagen synthesis or lipid peroxidation. In addition, no effect was seen with the oxygen radical scavengers isopropanol, ethanol, or dimethyl sulfoxide. Two iron chelators, o-phenanthroline and alpha,alpha-dipyridyl, both inhibited ascorbate-induced lipid peroxidation and collagen synthesis, consistent with the previously described iron-dependence of lipid peroxidation by ascorbate. These results support a correlation between collagen synthesis and lipid peroxidation and provide a theory for the mechanism of ascorbic acid regulation of collagen synthesis.