Glucocorticoid-mediated selective reduction of functioning collagen messenger ribonucleic acid.
Glucocorticoid-mediated selective reduction of functioning collagen messenger ribonucleic acid.
复制标题
糖皮质激素介导的功能性胶原信使核糖核酸的选择性减少。
DOI：
10.1016/0003-9861(81)90165-x
复制
发表时间：
1981
影响因子：
3.9
通讯作者：
Cutroneo,KR
中科院分区：
文献类型：
--
作者：
Rokowski,RJ;Sheehy,J;Cutroneo,KR
从新生大鼠肺和真皮中分离到多聚体，用寡聚(dT)-纤维素色谱法分离到多聚(A) RNA。RNA部分随后在放射性脯氨酸存在的核酸酶处理的网织细胞裂解物中翻译。在0.7 mmmagnesium和100 mm钾条件下，肺poly(A) RNA诱导的胶原蛋白和非胶原蛋白合成最佳。经聚丙烯酰胺凝胶电泳测定，RNA片段同时指导原α1和原α2链的合成。经胶原酶消化测定，从经双醋酸曲安奈德处理的大鼠的肺和真皮多体中分离的聚(A) RNA合成的胶原肽明显少于未处理动物的多体。非胶原蛋白合成的减少程度小于胶原蛋白合成。通过免疫沉淀测定，糖皮质激素处理不影响小麦胚芽提取物中的多体或核酸酶处理的网状细胞裂解液中的多体聚(A) RNA合成脯氨酸羟化酶的能力。这些数据表明，糖皮质激素介导的胶原多肽合成抑制不是由于对正常成纤维细胞总细胞蛋白合成的非特异性影响，而是选择性地减少多聚体相关信使RNA。此外，这些数据为合成抗炎类固醇选择性抑制胶原合成提供了分子基础。
Polysomes were isolated from both lung and dermis of neonatal rats and the poly(A) RNA therein was isolated by oligo(dT)-cellulose chromatography. The RNA fractions were then translated in the nuclease-treated reticulocyte lysate in the presence of radioactive proline. Optimal collagen and noncollagen protein synthesis directed by lung poly(A) RNA occurred at 0.7 mmmagnesium and 100 mmpotassium. The RNA fraction directed the synthesis of both proα1and proα2chains as determined by polyacrylamide gel electrophoresis. The poly(A) RNA isolated from both lung and dermis polysomes of rats treated with triamcinolone diacetate synthesized significantly less collagen peptides as determined by collagenase digestion as did the RNA isolated from polysomes of nontreated animals. Noncollagen protein synthesis was decreased to a lesser extent than collagen synthesis. Glucocorticoid treatment did not affect the ability of either polysomes in wheat germ extract or polysomal poly(A) RNA in nuclease-treated reticulocyte lysate to synthesize prolyl hydroxylase as determined by immunoprecipitation. These data indicate the glucorticoid-mediated inhibition of collagen polypeptide synthesis does not result from nonspecific effect on total cellular protein synthesis of normal fibroblasts, but a selective reduction of poly some-associated messenger RNA. Furthermore these data provide a molecular basis for selective inhibitory effect of synthetic anti-inflammatory steroids on collagen synthesis.