METHYL MERCURY INHIBITION OF SYNAPTOSOME AND BRAIN SLICE PROTEIN SYNTHESIS: IN VIVO AND IN VITRO STUDIES
METHYL MERCURY INHIBITION OF SYNAPTOSOME AND BRAIN SLICE PROTEIN SYNTHESIS: IN VIVO AND IN VITRO STUDIES
复制标题
甲基汞对突触体和脑切片蛋白质合成的抑制：体内和体外研究
DOI：
10.1111/j.1471-4159.1977.tb07785.x
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发表时间：
1977
影响因子：
4.7
通讯作者：
G. Czer
中科院分区：
文献类型：
--
作者：
M. Verity;W. Brown;M. Cheung;G. Czer
亚急性甲基汞（MeHg）中毒诱导成年大鼠每天灌胃1毫克甲基汞/100克体重。减少[14 C]亮氨酸掺入大脑和小脑切片蛋白被发现。体重减轻发生在潜伏期和神经毒性阶段，但对喂养没有发现一个显着的缺陷，氨基酸掺入切片蛋白。在潜伏期，突触体蛋白合成在体外没有下降，但在小脑和大脑突触体合成显着下降，发现在神经毒性阶段。在离体条件下，甲基汞在7.5 μ M和12.5 μM的半数最大浓度下分别抑制脑片和突触体蛋白质合成。对突触体合成的抑制与4 × 10− 6 M的K1是非竞争性的。甲基汞对突触体摄取[14 C]亮氨酸或[14 C]脯氨酸没有影响。当甲基汞浓度为12 μM时，突触体基础ATP酶和Na + K ATP酶均无明显抑制作用。氯霉素（55 S）或放线菌酮敏感的突触体组分蛋白质合成的抑制没有被发现的优先，这表明抑制是共同的线粒体和extramitarian蛋白质合成系统。此外，核苷酸和/或辛酸未能影响蛋白质的合成，并没有扭转甲基汞的抑制。甘露醇，作为替代的主要阳离子物种的孵育介质中，得到40%的抑制蛋白质合成的控制，但保护免受进一步抑制甲基汞。
Subacute methyl mercury (MeHg) intoxication was induced in adult rats following the daily intragastric administration of 1 mg MeHg/100 g body weight. Decreased [14C]leucine incorporation into cerebral and cerebellar slice protein was found. Weight loss occurred during the latent and neurotoxic phases but pair feeding did not reveal a significant defect in amino acid incorporation into slice protein. There was no decline in synaptosome protein synthesis in vitro during the latent phase but a significant decline in cerebellar and cerebral synaptosome synthesis was found during the neurotoxic phase. MeHg in vitro inhibited cerebral slice and synaptosome protein synthesis at half maximal concentrations of 7.5 and 12.5 μM respectively. Inhibition of synthesis in synaptosomes was non‐competitive with K1 of 4 × 10−6M. MeHg had no effect on [14C]leucine or [14C]proline uptake into synaptosomes. There was no significant inhibition of synaptosome basal ATPase or Na + K ATPase at concentrations of MeHg (12 μM) giving half maximal inhibition of protein synthesis. No preferential inhibition of the chloramphenicol (55S) or cycloheximide sensitive components of synaptosome fraction protein synthesis was found, suggesting that the inhibition is common to both mitochondrial and extramitochondrial protein synthesizing systems. Addition of nucleotides and/or atractylate failed to influence protein synthesis and did not reverse the MeHg inhibition. Mannitol, as a replacement for the predominant cation species of the incubation medium, gave 40% inhibition of protein synthesis in the control but protected against further inhibition by MeHg.