A specific decrease in collagen synthesis in acutely fasted, vitamin C-supplemented, guinea pigs.
A specific decrease in collagen synthesis in acutely fasted, vitamin C-supplemented, guinea pigs.
复制标题
严重禁食、补充维生素 C 的豚鼠胶原蛋白合成明显减少。
DOI：
10.1016/s0021-9258(18)89215-8
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
B. Peterkofsky
中科院分区：
文献类型：
--
作者：
R. Spanheimer;B. Peterkofsky
体重减轻通常由各种实验条件引起，包括豚鼠的坏血病，其中我们表明胶原蛋白合成减少与体重减轻直接相关，而不是与脯氨酸羟基化缺陷相关（Chojkier，M.，斯潘海默河和Peterkofsky，B.（1983）J. Clin. Invest. 72，826-835）。在这里描述的研究中，这种效果是由接受维生素C的急性禁食正常豚鼠复制的，通过测量胶原蛋白和非胶原蛋白的生产后，在体外标记组织与[3 H]脯氨酸。胶原蛋白的产生（dpm/微克DNA）开始禁食后不久下降，96小时达到对照值的8-12%。对非胶原蛋白的影响不太严重，因此在96小时禁食后，胶原蛋白合成相对于总蛋白合成的百分比为对照值的20-25%。这些影响不是由于游离脯氨酸的比放射性的变化。再喂养在24 h内逆转了对非胶原蛋白产生的影响，但胶原蛋白产生直到96 h才恢复正常。禁食对胶原蛋白生成的影响与年龄、性别、抗坏血酸状态、动物种属和结缔组织类型无关，也与体内标记有关。脉冲追踪实验和凝胶电泳分析标记和预先存在的蛋白质显示，没有证据表明增加胶原蛋白降解的结果禁食。通过无细胞翻译和cDNA探针斑点杂交测定，禁食动物组织中前胶原mRNA减少。相反，非胶原蛋白的可翻译mRNA没有减少。这些结果表明，维生素C以外的营养因子的损失导致胶原蛋白合成的快速，特异性减少，主要是通过调节mRNA水平。
Weight loss often results from various experimental conditions including scurvy in guinea pigs, where we showed that decreased collagen synthesis was directly related to weight loss, rather than to defective proline hydroxylation (Chojkier, M., Spanheimer, R., and Peterkofsky, B. (1983) J. Clin. Invest. 72, 826-835). In the study described here, this effect was reproduced by acutely fasting normal guinea pigs receiving vitamin C, as determined by measuring collagen and non-collagen protein production after labeling tissues in vitro with [3H]proline. Collagen production (dpm/microgram of DNA) decreased soon after initiating fasting and by 96 h it had reached levels 8-12% of control values. Effects on non-collagen protein were much less severe, so that the percentage of collagen synthesis relative to total protein synthesis was 20-25% of control values after a 96-h fast. These effects were not due to changes in the specific radioactivity of free proline. Refeeding reversed the effects on non-collagen protein production within 24 h, but collagen production did not return to normal until 96 h. The effect of fasting on collagen production was independent of age, sex, ascorbate status, species of animal, and type of connective tissue and also was seen with in vivo labeling. Pulse-chase experiments and analysis of labeled and pre-existing proteins by gel electrophoresis showed no evidence of increased collagen degradation as a result of fasting. Procollagen mRNA was decreased in tissues of fasted animals as determined by cell-free translation and dot-blot hybridization with cDNA probes. In contrast, there was no decrease in translatable mRNAs for non-collagen proteins. These results suggest that loss of nutritional factors other than vitamin C lead to a rapid, specific decrease in collagen synthesis mainly through modulation of mRNA levels.