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.
K Houglum, D A Brenner, M Chojkier
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Two different cis-acting regulatory regions direct cell-specific transcription of the collagen alpha 1(I) gene in hepatic stellate cells and in skin and tendon fibroblasts
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LAP (NF-IL6) transactivates the collagen alpha 1(I) gene from a 5' regulatory region
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Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: Localization and association with progression of liver fibrosis
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Stimulation of collagen α1(I) gene expression is associated with lipid peroxidation in hepatocellular injury: A link to tissue fibrosis?
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Loss of glomerular function and tubulointerstitial fibrosis:Cause or effect?
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Pathobiochemie, Molekularbiologie und moderne Diagnostik kardiovaskulärer Erkrankungen
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Free Radicals: from Basic Science to Medicine
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