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博来霉素对仓鼠肺切片中14C-脯氨酸摄取、其掺入蛋白质以及在胶原蛋白中的羟基化作用的影响。

Effects of bleomycin on 14C-proline uptake, its incorporation into proteins and hydroxylation in collagenous proteins of hamster lung slices.

作者信息

Giri S N, Younker W R, Schiedt M J

出版信息

J Appl Toxicol. 1985 Apr;5(2):89-93. doi: 10.1002/jat.2550050209.

Abstract

The uptake of 14C-proline by lung slices and its incorporation into trichloroacetic-acid (TCA)-insoluble proteins and hydroxylation in collagenous proteins were studied. They were found to be linearly increased with the incubation time for as long as 8 h. The effects of different concentrations of bleomycin on these parameters were subsequently investigated. Bleomycin at 10(-3) M significantly reduced the uptake of 14C-proline to 75% of the control value. The incorporation of 14C-proline into TCA-insoluble proteins was reduced to 84%, 78% and 75% of the control at 2.5 X 10(-4) M, 5 X 10(-4) M and 10(-3) M concentrations of bleomycin, respectively. Bleomycin failed to alter the proline pool size of the lung slices at any of these concentrations. In addition, bleomycin also inhibited the hydroxylation of 14C-proline into collagen to 72% and 69% of the control at 5 X 10(-4) M and 10(-3) M, respectively. These findings show that bleomycin-induced increases in collagen synthesis in vivo is probably secondary to inflammatory reactions of the lung and bleomycin per se has little effect on increased collagen synthesis responsible for lung fibrosis.

摘要

研究了肺切片对14C-脯氨酸的摄取及其掺入三氯乙酸(TCA)不溶性蛋白质中的情况以及在胶原蛋白中的羟基化情况。发现它们在长达8小时的孵育时间内呈线性增加。随后研究了不同浓度博来霉素对这些参数的影响。10(-3)M的博来霉素显著降低了14C-脯氨酸的摄取,降至对照值的75%。在博来霉素浓度为2.5×10(-4)M、5×10(-4)M和10(-3)M时,14C-脯氨酸掺入TCA不溶性蛋白质中的量分别降至对照值的84%、78%和75%。在这些浓度下,博来霉素均未改变肺切片中脯氨酸池的大小。此外,博来霉素在5×10(-4)M和10(-3)M时还分别将14C-脯氨酸在胶原蛋白中的羟基化抑制至对照值的72%和69%。这些发现表明,博来霉素在体内诱导的胶原蛋白合成增加可能继发于肺部的炎症反应,而博来霉素本身对导致肺纤维化的胶原蛋白合成增加影响很小。

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