Publications

Detailed Information

Oxidative stress attenuates Fas-mediated apoptosis in Jurkat T cell line through Bfl-1 induction

Cited 39 time in Web of Science Cited 40 time in Scopus
Authors

Kim, Heejung; Kim, Yong-Nyun; Kim, Hyungsoo; Kim, Chul-Woo

Issue Date
2004-12-14
Publisher
Nature Publishing Group
Citation
Oncogene 24: 1252-1261
Keywords
hydrogen peroxideapoptosisBfl-1NF-kappaB
Abstract
Many types of mammalian cells produce ROS in response to many different stimuli to modulate a number of cellular functions, including apoptosis. However, the correlation between ROS and apoptosis remains controversial, and the mechanisms whereby ROS-induced signals are propagated to critical downstream targets remain largely undefined. Here, we demonstrate that hydrogen peroxide (H2O2) upregulates the expression of Bfl-1, an antiapoptotic member of the Bcl-2 family, and that this is responsible for the antiapoptotic activity of ROS. When Jurkat, human leukemic T cells, were pretreated with 100 microM H2O2 and then treated with anti-Fas antibody, apoptosis was impaired without change of cell surface Fas expression. An investigation of the expression patterns of Bcl-2 family genes revealed that H2O2 treatment induced Bfl-1 gene expression, but left other genes unchanged, and this Bfl-1 expression and H2O2 -induced antiapoptotic effect was inhibited by antioxidants or NF-kappaB inhibitor. In addition, an electromobility shift assay revealed that the p65/p50 subunits of NF-kappaB activated by H2O2 bound to a bfl-1 promoter. Neither the induction of Bfl-1 nor the antiapoptotic effect of H2O2 was detected in Bfl-1-knockdown Jurkat cell line containing Bfl-1 antisense (Bfl-1AS). These data indicate that oxidative stress induces the expression of Bfl-1 via NF-kappaB activation, and this early-response gene protects cells from Fas-mediated apoptosis. This may be a cellular survival mechanism of cells exposed to phagocytes-derived ROS.
ISSN
0950-9232
Language
English
URI
https://hdl.handle.net/10371/9686
DOI
https://doi.org/10.1038/sj.onc.1208282
Files in This Item:
There are no files associated with this item.
Appears in Collections:

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share