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.
Geesin
J C
JC
Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854.
Hendricks
L J
LJ
Falkenstein
P A
PA
Gordon
J S
JS
Berg
R A
RA
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis*; D016166:Free Radical Scavengers; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*
D000975:Antioxidants; D001555:Benzene Derivatives; D002614:Chelating Agents; D016166:Free Radical Scavengers; D003094:Collagen; C007164:cumene hydroperoxide; D001205:Ascorbic Acid