Martin J L, Reed G F, Pohl L R
Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Biochem Pharmacol. 1993 Oct 5;46(7):1247-50. doi: 10.1016/0006-2952(93)90474-b.
We recently showed that when rats were administered the inhalation anesthetic halothane, a 58 kDa liver endoplasmic reticulum protein became covalently trifluoroacetylated by the trifluoroacetyl chloride metabolite of halothane. Although the 58 kDa protein showed 99% identity to that of the deduced amino acid sequence of a cDNA reported to correspond to phosphatidylinositol-specific phospholipase C-alpha, it did not have phosphatidylinositol-specific phospholipase C activity. It was concluded that the reported cDNA of phosphatidylinositol-specific phospholipase C-alpha actually encoded for the 58 kDa endoplasmic reticulum protein of unknown function. Other researchers have come to the same conclusion and have shown that the 58 kDa protein has protein disulfide-isomerase and protease activities. We now report that patients with halothane hepatitis have serum antibodies that react with both purified trifluoroacetylated and native rat liver 58 kDa proteins. These results suggest that when patients are exposed to halothane a human liver orthologue of the rat liver trifluoroacetylated-58 kDa protein is formed. In certain patients, this protein may become immunogenic and lead to the formation of specific antibodies and or specific T-cells, which may react with both trifluoroacetylated and native 58 kDa proteins, and ultimately be responsible, at least in part, for the hepatitis caused by halothane.
我们最近发现，当给大鼠吸入氟烷麻醉剂时，一种58 kDa的肝脏内质网蛋白会被氟烷的三氟乙酰氯代谢产物共价三氟乙酰化。尽管该58 kDa蛋白与一个据报道对应于磷脂酰肌醇特异性磷脂酶C-α的cDNA推导氨基酸序列的蛋白有99%的同一性，但它并不具有磷脂酰肌醇特异性磷脂酶C活性。得出的结论是，报道的磷脂酰肌醇特异性磷脂酶C-α的cDNA实际上编码的是功能未知的58 kDa内质网蛋白。其他研究人员也得出了相同的结论，并表明该58 kDa蛋白具有蛋白二硫键异构酶和蛋白酶活性。我们现在报告，氟烷性肝炎患者的血清抗体与纯化的三氟乙酰化大鼠肝脏58 kDa蛋白和天然大鼠肝脏58 kDa蛋白都发生反应。这些结果表明，当患者接触氟烷时，会形成大鼠肝脏三氟乙酰化-58 kDa蛋白的人肝脏同源物。在某些患者中，这种蛋白可能会变得具有免疫原性，并导致形成特异性抗体和/或特异性T细胞，它们可能与三氟乙酰化和天然58 kDa蛋白都发生反应，并最终至少部分地导致氟烷引起的肝炎。
