PRODUCTION OF MEMBRANE WHORLS IN RAT-LIVER BY SOME INHIBITORS OF PROTEIN-SYNTHESIS
PRODUCTION OF MEMBRANE WHORLS IN RAT-LIVER BY SOME INHIBITORS OF PROTEIN-SYNTHESIS
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DOI：
10.1083/jcb.62.1.20
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发表时间：
1974-01-01
影响因子：
7.8
通讯作者：
SARTORELLI, AC
中科院分区：
文献类型：
--
作者：
HWANG, KM;YANG, LC;SARTORELLI, AC
蛋白质合成抑制剂能够对膜结合和游离多聚核糖体上的新生肽合成产生不同的影响，以研究肝细胞膜的结构和功能。蛋白质合成的抑制剂（即放线菌酮和emethyl），主要是干扰新生肽的合成膜结合的多核糖体原位在细胞质中的膜涡的形成和核膜的扩张。其他蛋白质合成抑制剂，如嘌呤霉素和夫西地酸，抑制新生肽合成的自由和膜结合的多核糖体，氯霉素，抑制线粒体蛋白质合成，没有引起这些变化。放线菌酮、嘌呤霉素和氯霉素产生一些常见的细胞病变，如形态学上的类似改变所反映的，如线粒体肿胀、粗面内质网脱粒和游离核糖体聚集。螺旋形成的过程中，在细胞质中，[3 H]亮氨酸和[3 H]胆碱掺入内质网和总NADPH-细胞色素c还原酶活性的内质网进行了测定。在最大形成膜涡，pH]亮氨酸掺入细胞质膜被抑制，而[3 H]胆碱掺入这些结构增加;最大抑制蛋白质合成和刺激胆碱掺入内质网，然而，之前涡的形成。放线菌酮降低粗面内质网NADPH-细胞色素c还原酶活性，但增加滑面内质网NADPH-细胞色素c还原酶活性。放线菌酮还能降低大鼠肝微粒体和线粒体血红素蛋白的含量，并不同程度地降低混合功能氧化酶和氧化磷酸化的活性。琥珀酸刺激的微粒体氧化也受到抑制。本文还讨论了膜轮形成的可能机制及其功能。
Inhibitors of protein synthesis capable of differential effects on nascent peptide synthesis on membrane-bound and free polyribosomes were employed to investigate the structure and function of cellular membranes of liver. The formation of membranous whorls in the cytoplasm and distension of nuclear membranes were induced by inhibitors of protein synthesis (ie, cycloheximide and emetine) which predominantly interfere with nascent peptide synthesis on membrane-bound polyribosomes in situ. Other inhibitors of protein synthesis such as puromycin and fusidic acid, which inhibit nascent peptide synthesis on both free and membranebound polyribosomes, and chloramphenicol, which inhibits mitochondrial protein synthesis, did not induce these alterations. Cycloheximide, puromycin, and chloramphenicol produce some common cellular lesions as reflected by similar alterations in morphology, such as swelling of mitochondria, degranulation of rough endoplasmic reticulum, and aggregation of free ribosomes. The process of whorl formation in the cytoplasm, the incorporation of [3H] leucine and of [3H] choline into endoplasmic reticulum and the total NADPH-cytochrome c reductase activity of the endoplasmic reticulum were determined. During maximum formation of membranous whorls, pH] leucine incorporation into cytoplasmic membranes was inhibited, while [3H] choline incorporation into these structures was increased; maximum inhibition of protein synthesis and stimulation of choline incorporation into endoplasmic reticulum, however, preceded whorl formation. Cycloheximide decreased the activity of NADPH-cytochrome c reductase of rough endoplasmic reticulum, but increased NADPH-cytochrome c reductase activity of smooth endoplasmic reticulum. In addition, cycloheximide decreased the content of hemoprotein in both the microsomal and mitochondrial fractions of rat liver, and the activities of mixed function oxidase and of oxidative phosphorylation were impaired to different degrees. Succinate-stimulated microsomal oxidation was also inhibited. The possible mechanisms involved in the formation of membranous whorls, as well as their functions, are discussed.