D-alpha-tocopherol Inhibits Collagen Alpha 1(I) Gene Expression in Cultured Human Fibroblasts. Modulation of Constitutive Collagen Gene Expression by Lipid Peroxidation

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1991 Jun 1

PMID 2040703

Citations 11

Authors

K Houglum

D A Brenner

M Chojkier

Affiliations

Soon will be listed here.

Abstract

Ascorbic acid stimulates collagen gene transcription in cultured fibroblasts, and this effect is mediated through the induction of lipid peroxidation by ascorbic acid. Quiescent cultured fibroblasts in the absence of ascorbic acid have a high constitutive level of collagen production, but the mechanisms of collagen gene regulation in this unstimulated state are not known. Because lipid peroxidation also occurs in normal cells, we wondered if lipid peroxidation plays a role in the regulation of basal collagen gene expression. Inhibition of lipid peroxidation in cultured human fibroblasts with d-alpha-tocopherol or methylene blue decreased the synthesis of collagen, the steady-state levels of procollagen alpha 1(I) mRNA and the transcription of the procollagen alpha 1(I) gene. This effect on collagen gene expression was selective and not associated with cellular toxicity. Thus, these experiments suggest a role for lipid peroxidation in the modulation of constitutive collagen gene expression.

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