ASCORBIC-ACID AND COLLAGEN-SYNTHESIS - RETHINKING A ROLE FOR LIPID-PEROXIDATION
ASCORBIC-ACID AND COLLAGEN-SYNTHESIS - RETHINKING A ROLE FOR LIPID-PEROXIDATION
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DOI：
10.1006/abbi.1993.1596
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发表时间：
1993-12-01
影响因子：
3.9
通讯作者：
PINNELL, S
中科院分区：
文献类型：
--
作者：
DARR, D;COMBS, S;PINNELL, S
抗坏血酸积极影响胶原蛋白的合成，胶原蛋白是最丰富的细胞外蛋白。抗坏血酸介导的合成增加的机制是有争议的。最近的一个假说表明，抗坏血酸诱导脂质过氧化作用的增加，这种增加，以某种方式，上调胶原基因的表达。有证据表明，脂质过氧化[硫代巴比妥酸（TBA）反应性物质]的增加是巧合的抗坏血酸处理的细胞中的胶原蛋白的增加，而不是一个因果因素。因此，细胞不可渗透的铁螯合剂完全废除抗坏血酸介导的脂质过氧化作用，但不影响胶原蛋白的合成在最小。在较高的抗坏血酸水平下观察到的TBA反应产物的减少（指示众所周知的抗坏血酸体外的原抗氧化剂转化）被胶原合成的减少所抵消。在胶原蛋白中看到的减少是完全逆转的超氧化物歧化酶和过氧化氢酶的细胞培养物的治疗，而脂质过氧化的措施是不受这些抗氧化酶共孵育。此外，用于测量TBA反应性材料的抗坏血酸诱导的孵育条件（缓冲液与培养基，贴壁细胞与分离细胞）被发现是非常重要的，结果支持脂质过氧化和胶原蛋白合成可以分离的论点。虽然这些结果并不排除脂质介质在一定水平上调节胶原蛋白合成的作用，但它们表明这种机制不需要参与抗坏血酸处理细胞中观察到的胶原蛋白增加。
Ascorbic acid positively affects the synthesis of collagen, the most abundant extracellular protein. The mechanism by which ascorbate mediates the increased synthesis is debated. One recent hypothesis suggests that ascorbic acid induces an increase in lipid peroxidation and that this increase, in some manner, up-regulates collagen gene expression. Evidence is presented that indicate increases in lipid peroxidation [thiobarbituric acid (TBA)-reactive material] is coincidental to collagen increases in ascorbate-treated cells, not a causal factor. Thus, cell impermeable iron chelators totally abolish ascorbate-mediated lipid peroxidation but do not affect collagen synthesis in the least. Decreases in TBA-reactive products seen at higher ascorbate levels (indicative of the well known pro- to antioxidant conversion of ascorbatein vitro) are paralleled by decreases in collagen synthesis. The decrease seen in collagen is completely reversed by treatment of the cell cultures with superoxide dismutase and catalase while the measure of lipid peroxidation is unaffected by coincubation with these antioxidant enzymes. Additionally, incubation conditions used to measure ascorbate induction of TBA-reactive material (buffers vs media, adherent vs detached cells) were found to be very important and results support the thesis that lipid peroxidation and collagen synthesis can be dissociated. While these results do not rule out a role for lipid mediators in regulating collagen synthesis at some level, they suggest this mechanism need not be involved for collagen increases seen in ascorbic acid-treated cells.