Inhibition of Fas-mediated apoptosis by Trypanosoma cruzi infection
Inhibition of Fas-mediated apoptosis by Trypanosoma cruzi infection
复制标题
DOI：
10.1016/s0304-4165(00)00059-3
复制
发表时间：
2000-07-03
影响因子：
3
通讯作者：
Aoki, T
中科院分区：
文献类型：
--
作者：
Nakajima-Shimada, J;Zou, CB;Aoki, T
对克氏锥虫感染的和正常对照的哺乳动物细胞进行Fas介导的细胞凋亡分析，所述细胞凋亡由激动性抗Fas单克隆抗体刺激。感染的细胞表现出显着受阻的细胞核形态，磷脂酰乙醇胺易位从内到外的质膜，DNA片段成180 bp的倍数，相对于正常对照细胞的凋亡变化。上游的这些形态学和生化的后果，caspase-3活性升高的Fas刺激在一个显着更大比例的完整的控制细胞，但在一个高度降低的感染细胞。对照组caspase-8活性迅速升高，感染组凋亡细胞完全被抑制。在检查其他兴奋剂的特异性，X射线辐射或化学品，如过氧化氢，秋水仙碱或依托泊苷没有引起控制和感染细胞之间的凋亡率的显着差异;肿瘤坏死因子-α，然而，诱导控制细胞的凋亡率高，在感染细胞的凋亡率极低。本研究首次证明T. Cruzi感染抑制死亡受体介导的细胞凋亡的最早步骤之一，该作用最可能涉及半胱天冬酶-8的抑制。T. cruzi和其他细胞内寄生虫进行了讨论。(C)2000 Elsevier Science B. V.保留所有权利。
Trypanosoma cruzi-infected and normal control mammalian cells were subjected to analysis of Fas-mediated apoptosis stimulated by an agonistic anti-Fas monoclonal antibody. The infected cells showed markedly hampered apoptotic changes in nuclear morphology, phosphatidylethanolamine translocation from the inside to the outside of the plasma membrane, and DNA fragmentation into multiples of 180 bp, relative to normal control cells. Upstream of these morphological and biochemical consequences, the caspase-3 activity was elevated by the Fas stimulation in a significantly greater proportion of intact control cells, but at a highly reduced rate of infected cells. The rapid elevation of caspase-8 activity in control, apoptotic cells was completely inhibited in infected cells. In an examination of the specificity of other stimulants, X-ray radiation or chemicals such as hydrogen peroxide, colchicine or etoposide did not cause significant differences in apoptotic rates between control and infected cells; tumor necrosis factor-alpha, however, induced a high rate of apoptosis in control cells, with an extremely lowered rate in infected cells. This study demonstrates, for the first time, that T. cruzi infection inhibits one of the earliest steps of death receptor-mediated apoptosis, an effect that most probably involves the inhibition of caspase-8. Differential apoptotic responses in cells infected with T. cruzi and other intracellular parasites are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.