Denk H, Bernklau G, Krepler R
Liver. 1984 Jun;4(3):208-13. doi: 10.1111/j.1600-0676.1984.tb00929.x.
The present study was undertaken in order to elucidate the effect of liver injury exerted by the antimicrotubular drug griseofulvin on hepatic transglutaminase activity in mice. Griseofulvin treatment of mice leads to a significant increase of transglutaminase activity associated with the 105 000 X g supernatant of liver homogenate, which is readily reversible after replacement of the griseofulvin-containing diet by a normal diet. Neoplastic nodules originally induced by prolonged griseofulvin feeding also show increased transglutaminase activity in contrast to reports in the literature. The increase in hepatic transglutaminase activity in griseofulvin-fed mice could be due either to mitotic inhibition exerted by the drug or to disturbance of intracellular Ca++ homeostasis following membrane injury. The second possibility could also account for the increased enzyme activity in neoplastic nodules. Similar events have been described as occurring in aging erythrocytes and terminally differentiating keratinocytes. The pathologic consequences and the substrates of increased hepatic transglutaminase activity have still to be elucidated.
本研究旨在阐明抗微管药物灰黄霉素对小鼠肝脏转谷氨酰胺酶活性造成的肝损伤作用。用灰黄霉素处理小鼠会导致与肝脏匀浆105 000×g上清液相关的转谷氨酰胺酶活性显著增加，在用正常饮食替代含灰黄霉素的饮食后，这种增加很容易逆转。与文献报道相反，长期喂食灰黄霉素最初诱导的肿瘤结节也显示出转谷氨酰胺酶活性增加。喂食灰黄霉素的小鼠肝脏转谷氨酰胺酶活性增加可能是由于该药物施加的有丝分裂抑制，或者是膜损伤后细胞内Ca++稳态的紊乱。第二种可能性也可以解释肿瘤结节中酶活性的增加。类似的事件已被描述为发生在衰老的红细胞和终末分化的角质形成细胞中。肝脏转谷氨酰胺酶活性增加的病理后果和底物仍有待阐明。
