Pulatova M K, Sharygin V L, Mitrokhin Iu I, Todorov I N
Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 119991 Russia.
Biofizika. 2003 Nov-Dec;48(6):1094-107.
Time-dependent responses of cellular systems in rat organs and Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in blood to the blocking of translation by sublethal doses of cycloheximide (CHI) was studied by EPR spectroscopy and radioisotope techniques. It was shown that, within the early post-CHI-treatment time, the suppression of deoxyribonucleotide and DNA biosynthesis, the activation of catabolic enzymes, the inhibition of electron transfer in the mitochondrial electron transport chain, the activation and the following inactivation of cytochrome P-450, and an intensive production of nitrosyl complexes in rat blood and organs occur. In addition, the activation of the synthesis of steroid hormones in adrenal gland was revealed within 1-24 h after cycloheximide injection. In response to these metabolic disturbances, nonspecific compensatory recovery reactions developed, first of all, the "reprograming" of the translation process to produce new protein-synthesizing elements instead of cycloheximide-blocked ones. The activation of protein synthesis promotes the recovery of deoxyribonucleotide and DNA synthesis, the restoration of the redox state of mitochondrial and microsomal electron transport chains in organs as well as an increase of Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in rat blood. These metabolic processes result in the full recovery of the functional ability of organs.
采用电子顺磁共振波谱法和放射性同位素技术,研究了大鼠器官细胞系统以及血液中Fe(3+)-转铁蛋白和Cu(2+)-铜蓝蛋白池对亚致死剂量环己酰亚胺(CHI)阻断翻译的时间依赖性反应。结果表明,在CHI处理后的早期,大鼠血液和器官中会出现脱氧核苷酸和DNA生物合成受抑制、分解代谢酶被激活、线粒体电子传递链中电子传递受抑制、细胞色素P-450先被激活后失活以及亚硝酰复合物大量产生等情况。此外,注射环己酰亚胺后1-24小时内,肾上腺中甾体激素的合成被激活。针对这些代谢紊乱,机体出现了非特异性的代偿性恢复反应,首先是翻译过程的“重新编程”,以产生新的蛋白质合成元件来替代被环己酰亚胺阻断的元件。蛋白质合成的激活促进了脱氧核苷酸和DNA合成的恢复、器官中线粒体和微粒体电子传递链氧化还原状态的恢复以及大鼠血液中Fe(3+)-转铁蛋白和Cu(2+)-铜蓝蛋白池的增加。这些代谢过程导致器官功能能力完全恢复。