Houglum K, Brenner D A, Chojkier M
Department of Medicine, Veterans Affairs Medical Center, San Diego, California.
J Clin Invest. 1991 Jun;87(6):2230-5. doi: 10.1172/JCI115258.
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.
抗坏血酸可刺激培养的成纤维细胞中胶原蛋白基因的转录，且这种作用是通过抗坏血酸诱导脂质过氧化作用介导的。在无抗坏血酸的情况下，静止的培养成纤维细胞具有较高的组成性胶原蛋白生成水平，但在这种未受刺激状态下胶原蛋白基因调控的机制尚不清楚。由于脂质过氧化作用也发生在正常细胞中，我们想知道脂质过氧化作用是否在基础胶原蛋白基因表达的调控中发挥作用。用d-α-生育酚或亚甲蓝抑制培养的人成纤维细胞中的脂质过氧化作用，可降低胶原蛋白的合成、前胶原α1（I）mRNA的稳态水平以及前胶原α1（I）基因的转录。这种对胶原蛋白基因表达的影响具有选择性，且与细胞毒性无关。因此，这些实验表明脂质过氧化作用在组成性胶原蛋白基因表达的调节中发挥作用。
