Hydrogen peroxide induced down-regulation of CD28 expression of Jurkat cells is associated with a change of site alpha-specific nuclear factor binding activity and the activation of caspase-3.
CD28 is the requisite co-stimulatory molecule in the activation of T cells and in the generation of immune responses. But expression of CD28 declined and oxidants accumulated in the elderly. Although accumulation of reactive oxygen species (ROS) during senescence has been reported extensively, the effect of oxidants on CD28-expression remains totally unknown. In this study, we tried to address the molecular mechanism underlying the decrease in CD28-expression of Jurkat T cells cultured in H2O2. Our results indicate that H2O2 could partially block the expression of CD28. This correlates well with a change of nuclear protein binding activity to the motif of site alpha of the CD28 gene, while the site beta-binding activity remained unaltered. On the other hand, since caspase-3 is activated by H2O2, inhibitors of caspase-3 should increase the expression of CD28. What is more interesting is the fact that the site alpha-binding activity was mostly restored after caspase-3 inhibitors had being added. However, caspase-3 is not activated by caspase-8. Maybe it is activated by caspase-9, which is triggered by cytochrome c. We believe that the procaspase-3 is activated by ROS, and the active caspase-3 can induce the change of the site alpha-binding activity, causing a decrease in CD28 expression.
Ma
Shibin
S
Department of Immunology, Institute of Basic Medical sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, People's Republic of China.
Ochi
Hirotomo
H
Cui
Lianxian
L
Zhang
Jianmin
J
He
Wei
W
D000375:Aging / Q000276:immunology; D018106:CD28 Antigens / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019169:Jurkat Cells; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D018106:CD28 Antigens; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases