Protein metabolism during bleomycin-induced pulmonary fibrosis in rabbits. In vivo evidence for collagen accumulation because of increased synthesis and decreased degradation of the newly synthesized collagen.

Protein metabolism during bleomycin-induced pulmonary fibrosis in rabbits. In vivo evidence for collagen accumulation because of increased synthesis and decreased degradation of the newly synthesized collagen.
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DOI:
10.1164/arrd.1983.128.1.82
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发表时间:
1983-07
期刊:
The American review of respiratory disease
影响因子:
--
通讯作者:
G. Laurent;R. McAnulty
G. Laurent;R. McAnulty
中科院分区:
其他
文献类型:
--
作者:
G. Laurent;R. McAnulty

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在正常肺和博莱霉素诱导的兔肺纤维化的前14天,在体内测定胶原和非胶原蛋白的合成和降解速率。蛋白质合成率通过测量标记的脯氨酸掺入组织蛋白后,注射3 H-脯氨酸与大量的未标记的脯氨酸。通过几种独立的方法评估降解速率,包括测量无组织池中的羟基-3H-脯氨酸作为新合成胶原降解的指标。在正常肺中,胶原蛋白以9.5 +/- 1.5%/天的速率合成和降解,而非胶原蛋白的速率为34.6 +/- 1.9%/天。大约三分之一的新合成的胶原蛋白在产生后迅速降解。博莱霉素给药后6天,胶原合成率几乎翻了一番,非胶原蛋白的合成率增加了约35%。此时,新合成的胶原蛋白的降解率降低了约30%。从这项研究中,我们得出结论:(1)肺在蛋白质代谢方面是活跃的组织,胶原和非胶原蛋白都具有快速的周转,和(2)增加的合成速率和降低的降解速率有助于在肺纤维化的早期阶段胶原的快速积累。
In vivo rates of synthesis and degradation of collagen and noncollagen protein were measured in normal lung and during the first 14 days of bleomycin-induced pulmonary fibrosis in rabbits. Protein synthesis rates were obtained by measuring the incorporation of labeled proline into tissue proteins after the injection of 3H-proline with a large amount of unlabeled proline. Degradation rates were assessed by several independent methods, including measurement of hydroxy-3H-proline in the tissue-free pool as an index of the degradation of newly synthesized collagen. In normal lung, collagen was synthesized and degraded at a rate of 9.5 +/- 1.5%/day compared with a rate of 34.6 +/- 1.9%/day for noncollagen proteins. About one third of the newly synthesized collagen was degraded rapidly after its production. Six days after bleomycin administration the collagen synthesis rate almost doubled and the synthesis rate of noncollagen protein increased by about 35%. At this time the degradation rate of newly synthesized collagen had decreased by about 30%. From this study we conclude: (1) that the lung is an active tissue in terms of protein metabolism with rapid turnover for both collagen and noncollagen proteins, and (2) that an increased rate of synthesis and a decreased rate of degradation contribute to rapid accumulation of collagen in the early stages of pulmonary fibrosis.