Sutton P, Beaver J, Waring P
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia.
Biochem Pharmacol. 1995 Dec 22;50(12):2009-14. doi: 10.1016/0006-2952(95)02101-9.
Gliotoxin is a secondary metabolite produced by several pathogenic fungi. It has potential clinical applications as an immunosuppressive agent in preventing allograft rejection. At low doses (< 30 nM) gliotoxin displays co-mitogenic activity, but at higher doses induces apoptosis in cells. Here we demonstrate that gliotoxin, although not mitogenic in its own right, enhances activation in preactivated splenocytes by a calcium-independent mechanism. The enhancement in activation correlates with a decrease in intracellular cyclic AMP levels. This property is inhibited by dibutyryl-cAMP. Increasing the concentration of gliotoxin to levels that caused apoptosis produced a dose-related increase in cAMP levels. Thus, the effects of gliotoxin on cell activation and the induction of apoptosis may both be mediated by changed levels of cAMP.
Gliotoxin是几种致病真菌产生的次生代谢产物。它作为一种免疫抑制剂在预防同种异体移植排斥反应方面具有潜在的临床应用价值。在低剂量（<30 nM）时，Gliotoxin表现出共促有丝分裂活性，但在高剂量时会诱导细胞凋亡。在这里，我们证明Gliotoxin虽然本身没有促有丝分裂作用，但通过一种不依赖钙的机制增强预激活脾细胞的活化。活化增强与细胞内环状AMP水平降低相关。这种特性被二丁酰环磷腺苷抑制。将Gliotoxin浓度增加到导致细胞凋亡的水平会使cAMP水平产生剂量相关的增加。因此，Gliotoxin对细胞活化和细胞凋亡诱导的作用可能都由cAMP水平的变化介导。
