Depression of cytochrome P-450 and alterations of protein metabolism in mice treated with the interferon inducer polyriboinosinic acid X polyribocytidylic acid.
Depression of cytochrome P-450 and alterations of protein metabolism in mice treated with the interferon inducer polyriboinosinic acid X polyribocytidylic acid.
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用干扰素诱导剂聚核糖肌苷酸 X 聚核糖胞苷酸治疗的小鼠中细胞色素 P-450 的抑制和蛋白质代谢的改变。
DOI：
10.1016/0003-9861(86)90744-7
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发表时间：
1986
影响因子：
3.9
通讯作者：
Mannering,GJ
中科院分区：
文献类型：
--
作者：
Gooderham,NJ;Mannering,GJ
摘要干扰素诱导剂聚核糖核酸[Poly(IC)]处理小鼠，可抑制多种肝脏蛋白质的表达。在这项研究中，我们检测了用聚(IC)处理的小鼠肝细胞细胞器蛋白质的合成和降解。[14 C]-和L-[3 H]亮氨酸分别掺入对照和多聚(IC)处理的小鼠体内，观察其对合成的影响。在Poly(IC)处理后的特定时间，建立核、线粒体、溶酶体、光滑内质网、粗面内质网和105,000 g上清液(胞浆)的Sol 3 H 14 C比率。溶酶体组分和粗面内质网组分的从头蛋白合成随时间变化最大；治疗9h后两者均受到抑制。用[14C]碳酸氢盐测定聚(IC)对蛋白质降解的影响。Poly(IC)治疗可缩短14C标记蛋白50%消失所需的时间(T12)，减少光滑和粗糙内质网的消失。内质网标志物酶检测显示，细胞色素P-450和b5在给予Poly(IC)后9h开始受到抑制。Poly(IC)处理6h后酪氨酸氨基转移酶活性升高，9h后活性下降，其他细胞器标志酶未见明显变化。我们的结论是，聚(IC)通过降低蛋白质合成速率和增加蛋白质降解速率来降低肝脏内质网蛋白质的含量，包括某些细胞色素P-450同工酶。
Abstract Treatment of mice with the interferon inducer polyriboinosinic acid· polyribocytidylic acid [poly (IC)] results in the depression of several hepatic proteins. In this study we examined synthesis and degradation of the proteins of liver cell organelles in mice treated with poly (IC). Effects on synthesis were determined by using [14 C]-and L-[3 H] leucine incorporation into control and poly (IC)-treated mice, respectively. At selected times after poly (IC) treatment the sol 3 H 14 C ratio was established for preparations of nuclei, mitochondria, lysosomes, smooth endoplasmic reticulum, rough endoplasmic reticulum, and 105,000 g supernatant (cytosol). Time-dependent alterations in de novo protein synthesis were greatest in lysosomal and rough endoplasmic reticular fractions; both were depressed 9 h after treatment. The effects of poly (IC) on protein degradation were determined with [14 C] bicarbonate. Poly (IC) treatment decreased the time required for disappearance of 50% of 14 C-labeled protein (t 1 2 of smooth and rough endoplasmic reticula. Examination of endoplasmic reticulum marker enzymes showed depression of cytochromes P-450 and b 5 from 9 h onward after poly (IC) administration. Tyrosine aminotransferase activity was elevated 6 h after treatment with poly (IC), and then depressed after 9 h. The other organelle marker enzymes were not affected significantly. We conclude that poly (IC) decreases the content of proteins of the hepatic endoplasmic reticulum, including certain cytochrome P-450 isozymes, by decreasing rates of protein synthesis and increasing rates of protein degradation.