ASCORBATE DEFICIENCY RESULTS IN DECREASED COLLAGEN PRODUCTION - UNDER-HYDROXYLATION OF PROLINE LEADS TO INCREASED INTRACELLULAR DEGRADATION
ASCORBATE DEFICIENCY RESULTS IN DECREASED COLLAGEN PRODUCTION - UNDER-HYDROXYLATION OF PROLINE LEADS TO INCREASED INTRACELLULAR DEGRADATION
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DOI：
10.1016/0003-9861(83)90338-7
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发表时间：
1983-01-01
影响因子：
3.9
通讯作者：
CRYSTAL, RG
中科院分区：
文献类型：
--
作者：
BERG, RA;STEINMANN, B;CRYSTAL, RG
当细胞缺乏抗坏血酸时，检测培养的人肺成纤维细胞的胶原蛋白产生。在6小时标记期间，在不存在抗坏血酸盐的情况下生长的细胞比在标记期间用低至1 μ g/ml抗坏血酸盐孵育的细胞少产生30%的胶原。无抗坏血酸生长的细胞产生羟基化胶原蛋白不足，其经历从所有新合成胶原蛋白的16%的基础水平到49%的增强水平的增加的细胞内降解。细胞内降解增加的可能机制是羟基化不足的胶原蛋白无法呈现三螺旋构象，导致其易于细胞内降解。使用针对胶原蛋白三螺旋决定簇的抗体通过酶联免疫测定法（ELISA）测量胶原蛋白的产生，结果表明I型和III型胶原蛋白都受到影响。另一种结缔组织成分，纤维连接蛋白，没有受到影响。ELISA分析显示，胶原蛋白产量的减少幅度大于胶原酶法分析，这表明在不存在抗坏血酸的情况下分泌了一些非螺旋胶原蛋白链（通过胶原酶检测，但通过ELISA检测不到）。这些结果提供了一种机制，部分地解释了在抗坏血酸缺乏的状态下发生的结缔组织中胶原蛋白的缺乏。
Collagen production by cultured human lung fibroblasts was examined when the cells were made deficient in ascorbate. Cells grown in the absence of ascorbate produced 30% less collagen during a 6-h labeling period than cells incubated with as little as 1 .mu.g/ml ascorbate during the labeling period. Cells grown without ascorbate produced under-hydroxylated collagen which was subject to increased intracellular degradation from a basal level of 16% to an enhanced level of 49% of all newly synthesized collagen. The likely mechanism for increased intracellular degradation is the inability of underhydroxylated collagen to assume a triple-helical conformation causing it to be susceptible to intracellular degradation. Measurement of collagen production by enzyme linked immunoassay (ELISA) using antibodies directed against triple-helical determinants of collagen showed that both types I and III collagens were affected. Another connective tissue component, fibronectin, was not affected. Analysis by ELISA showed a greater decrease in collagen production than did analysis by the collagenase method, suggesting that some non-helical collagen chains (detected by collagenase but not by ELISA) were secreted in the absence of ascorbate. These results provide a mechanism to account, in part, for the deficiency of collagen in connective tissues which occur in a state of ascorbate deficiency.