BOTH HUMAN FAS AND CHIMERIC FAS TNFR-1 MEDIATE COMPLETE CELL-DEATH INMURINE NIH/3T3 CELLS WITH LESS DISTINCT NUCLEAR FRAGMENTATION/

Citation
T. Yoshida et al., BOTH HUMAN FAS AND CHIMERIC FAS TNFR-1 MEDIATE COMPLETE CELL-DEATH INMURINE NIH/3T3 CELLS WITH LESS DISTINCT NUCLEAR FRAGMENTATION/, Proceedings of the Japan Academy. Series B Physical and biological sciences, 72(1), 1996, pp. 16-21
Citations number
30
Categorie Soggetti
Multidisciplinary Sciences",Biology
ISSN journal
03862208
Volume
72
Issue
1
Year of publication
1996
Pages
16 - 21
Database
ISI
SICI code
0386-2208(1996)72:1<16:BHFACF>2.0.ZU;2-N
Abstract
Necrotic and apoptotic changes have been rather conceptually defined, and have shown varying morphological and biochemical features dependin g on signaling pathways and cell lineages. In an attempt to investigat e apoptotic and necrotic signals, we constructed a chimer ic gene enco ding an extracellular human Fas and intracytoplasmic human TNFR-1 (TNF receptor p55) and introduced it into murine NIH/3T3 cells for their h eterotopic expression. Upon stimulation with an agonistic anti-human F as monoclonal antibody those NIH/3T3 cell clones with the chimeric rec eptor showed cytopathic changes quite similar to those with the wild t ype Fas, although both receptors possess 'death' domains with differen t binding proteins. In this forced induction of death of the fibroblas tic cells, we found thus that: 1) Fas signal induced complete cell dea th, 2) cytopathic changes in both NIH/3T3 derivatives were quite simil ar with irregular nuclear fragmentation and less distinct DNA fragment ation, and 3) intracytoplasmic domains were interchangeable between Fa s and TNFR-1. This system may contribute to further analyses of the ce ll death mechanisms, including downstream Fas/TNFR-1 signaling.