Inhibition of Fas-mediated apoptosis by Trypanosoma cruzi infection

Citation
J. Nakajima-shimada et al., Inhibition of Fas-mediated apoptosis by Trypanosoma cruzi infection, BBA-GEN SUB, 1475(2), 2000, pp. 175-183
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
ISSN journal
0304-4165 → ACNP
Volume
1475
Issue
2
Year of publication
2000
Pages
175 - 183
Database
ISI
SICI code
0304-4165(20000703)1475:2<175:IOFABT>2.0.ZU;2-E
Abstract
Trypanosoma cruzi-infected and normal control mammalian cells were subjecte d 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 in to multiples of 180 bp, relative to normal control cells. Upstream of these morphological and biochemical consequences, the caspase-3 activity was ele vated by the Fas stimulation in a significantly greater proportion of intac t 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, colchic ine or etoposide did not cause significant differences in apoptotic rates b etween control and infected cells; tumor necrosis factor-alpha, however, in duced 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-medi ated apoptosis, an effect that most probably involves the inhibition of cas pase-8. Differential apoptotic responses in cells infected with T. cruzi an d other intracellular parasites are discussed. (C) 2000 Elsevier Science B. V. All rights reserved.