Zatloukal K, Fesus L, Denk H, Tarcsa E, Spurej G, Böck G
Laboratory of Molecular Pathology, University of Graz School of Medicine, Austria.
Lab Invest. 1992 Jun;66(6):774-7.
Alcoholic hepatitis, the most severe form of alcoholic liver disease, is associated with inflammation, liver cell necrosis, and the appearance of Mallory bodies (MBs) in hepatocytes. Identical MBs can be experimentally induced in mouse livers by chronic griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine treatment. MBs are filamentous cytoplasmic inclusions containing insoluble high molecular weight protein material. Covalent polymerization of intracellular proteins may occur through formation of epsilon-(gamma-glutamyl)lysine cross-links catalyzed by Ca(2+)-dependent transglutaminases. Therefore, isolated experimentally-induced MBs were analyzed for the presence of epsilon-(gamma-glutamyl)lysine bonds. Highly purified MBs contained 19.7 nmole (griseofulvin-induced) and 14.4 nmoles (3,5-diethoxycarbonyl-1,4-dihydrocollidine induced) of isodipeptide linkage, respectively, per mg of protein. These results suggest that transglutaminase-induced cross-linking of proteins plays a major role in MB formation.
酒精性肝炎是酒精性肝病最严重的形式，与炎症、肝细胞坏死以及肝细胞中马洛里小体（MBs）的出现有关。通过长期给予灰黄霉素或3,5 - 二乙氧基羰基 - 1,4 - 二氢可力丁处理，可在小鼠肝脏中实验性诱导出相同的马洛里小体。马洛里小体是含有不溶性高分子量蛋白质物质的丝状细胞质内含物。细胞内蛋白质的共价聚合可能通过钙（2 +）依赖性转谷氨酰胺酶催化形成ε -（γ - 谷氨酰基）赖氨酸交联而发生。因此，对实验诱导分离出的马洛里小体进行了ε -（γ - 谷氨酰基）赖氨酸键的分析。高度纯化的马洛里小体每毫克蛋白质分别含有19.7纳摩尔（灰黄霉素诱导）和十四点四纳摩尔（3,5 - 二乙氧基羰基 - 1,4 - 二氢可力丁诱导）的异二肽键。这些结果表明，转谷氨酰胺酶诱导的蛋白质交联在马洛里小体形成中起主要作用。
