Ubiquitin metabolism affects cellular response to volatile anesthetics in yeast.
Ubiquitin metabolism affects cellular response to volatile anesthetics in yeast.
复制标题
泛素代谢影响酵母中挥发性麻醉剂的细胞反应。
DOI：
10.1128/mcb.19.12.8254
复制
发表时间：
1999
影响因子：
5.3
通讯作者：
Keil,RL
中科院分区：
文献类型：
--
作者：
Wolfe,D;Reiner,T;Keeley,JL;Pizzini,M;Keil,RL
为了研究挥发性麻醉剂的作用机制，我们正在研究酵母菌的突变体，这些突变体改变了对异氟烷（一种广泛使用的临床麻醉剂）的敏感性。这些研究中的几条证据暗示了泛素代谢在细胞对挥发性麻醉剂的反应中的作用：（i）ZZZ 1基因的突变使细胞对异氟烷产生抗性，并且ZZZ 1基因与BUL 1相同（结合泛素连接酶），其似乎参与泛素化途径;（ii）ZZZ 4基因与DOA 1/UFD 3基因完全相同，而DOA 1/UFD 3基因是基于泛素化蛋白质降解的改变而鉴定的;（iii）对zzz 1 Δ zzz 4 Δ双突变体的分析表明，这些基因编码参与麻醉反应的相同途径的产物，因为双突变体对麻醉剂的抗性不比单突变体亲本中的任一个更强;（iv）泛素连接酶（V）具有降低的蛋白酶体活性的突变体对异氟烷具有抗性。ZZZ 1和MDP 1/RSP 5基因产物似乎在确定酵母中的有效麻醉剂量方面发挥着重要作用，因为这两种基因的水平增加会增加异氟烷的敏感性，而活性降低会降低敏感性。像zzz 4菌株，zzz 1突变体是耐所有五种挥发性麻醉剂测试，这表明有各种挥发性麻醉剂在酵母中的作用机制的相似性，泛素代谢影响对所有的代理商检查。
To investigate the mechanism of action of volatile anesthetics, we are studying mutants of the yeastSaccharomyces cerevisiaethat have altered sensitivity to isoflurane, a widely used clinical anesthetic. Several lines of evidence from these studies implicate a role for ubiquitin metabolism in cellular response to volatile anesthetics: (i) mutations in theZZZ1gene render cells resistant to isoflurane, and theZZZ1gene is identical toBUL1(binds ubiquitin ligase), which appears to be involved in the ubiquitination pathway; (ii)ZZZ4, which we previously found is involved in anesthetic response, is identical to theDOA1/UFD3gene, which was identified based on altered degradation of ubiquitinated proteins; (iii) analysis ofzzz1Δ zzz4Δdouble mutants suggests that these genes encode products involved in the same pathway for anesthetic response since the double mutant is no more resistant to anesthetic than either of the single mutant parents; (iv) ubiquitin ligase (MDP1/RSP5) mutants are altered in their response to isoflurane; and (v) mutants with decreased proteasome activity are resistant to isoflurane. TheZZZ1andMDP1/RSP5gene products appear to play important roles in determining effective anesthetic dose in yeast since increased levels of either gene increases isoflurane sensitivity whereas decreased activity decreases sensitivity. Likezzz4strains,zzz1mutants are resistant to all five volatile anesthetics tested, suggesting there are similarities in the mechanisms of action of a variety of volatile anesthetics in yeast and that ubiquitin metabolism affects response to all the agents examined.