ISSN:
1573-675X
Keywords:
Apoptosis
;
caspase-3
;
somatic cell hybridization
;
TNFα
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract Tumour necrosis factor-α (TNFα) is a cytokine that induces apoptosis in various cell systems by binding to a TNF receptor (TNFR). To study TNFα-induced apoptosis, we isolated and characterized a novel TNFα resistant variant, U937/TNF clone II-5, from human monocytic leukaemia U937 cells. The II-5 cells resist apoptosis by TNFα and anti-Fas antibody but not by anticancer drugs, such as VP-16 and Ara-C. Somatic cell hybridization between U937 and II-5 showed that the apoptosis resistance to TNFα in II-5 was genetically dominant. This dominant mutation in II-5 cells blocks TNFα-induced disruption of mitochondrial membrane potential and caspase-3 activation. Expression of TNFR, Fas and Bcl-2 family proteins were not changed in II-5 cells. These results suggest that the apoptosis-resistant II-5 cells could have a functional defect in apoptosis signalling from TNFR to mitochondria and caspase activation. The II-5 cells could be useful in studying the signa lling linkage between TNFR and mitochondria.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1009657008098
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