Abstract:
:Reactive oxygen species (ROS) mediate apoptosis in many different cell types. We have previously shown that the antioxidant Mn(III) tetrakis(5,10,15,20-benzoic acid)porphyrin (MnTBAP) decreased intracellular ROS and prevented the apoptosis of activated T cells in vitro. To determine the mechanism(s) by which MnTBAP afforded such protection, we used Affymetrix (Santa Clara, CA) gene arrays to compare gene expression in T cells activated with staphylococcal enterotoxin B in vivo then cultured with or without MnTBAP. This analysis showed that the antioxidant increased the expression of Bcl-2, an antiapoptotic molecule whose levels are normally decreased by T cell activation. Culture with MnTBAP revealed a tight inverse correlation between the levels of Bcl-2 and ROS within T cells. In vivo, production of ROS in activated T cells occurred before Bcl-2 down-regulation. Furthermore, MnTBAP's ability to prevent death required the expression of Bcl-2 in most T cells. Finally, neither ROS production nor the effects on Bcl-2 expression required Bim, the Bcl-2 antagonist that mediates the death of activated T cells in vivo. Taken together, our results suggest that ROS sensitize T cells to apoptosis by decreasing expression of Bcl-2.
journal_name
Proc Natl Acad Sci U S Aauthors
Hildeman DA,Mitchell T,Aronow B,Wojciechowski S,Kappler J,Marrack Pdoi
10.1073/pnas.1936213100keywords:
subject
Has Abstractpub_date
2003-12-09 00:00:00pages
15035-40issue
25eissn
0027-8424issn
1091-6490pii
1936213100journal_volume
100pub_type
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