Inhibition of CREB transcriptional activity in human T lymphocytes by oxidative stress.
Hydrogen peroxide (HP) induced the phosphorylation of cAMP response element binding protein (CREB) on Ser133 in Jurkat T lymphocytes via p38 and MSK1. Although CREB Ser133 was phosphorylated, increases in HP-stimulated CREB-mediated transcription were absent. T lymphocyte stimulation with anti-CD3 and anti-CD28 induced CREB Ser133 phosphorylation, as well as CREB-mediated transcriptional activity. When CD3/CD28-stimulated lymphocytes were treated with HP, Ser133 was phosphorylated, but TCR-induced CREB-mediated transcriptional activity was reduced. These data provide insight into a potential mechanism by which oxidative stress can alter T cell receptor-induced CREB activation and responsiveness.
Rodriguez-Mora
Oswaldo G
OG
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Howe
Christopher J
CJ
Lahair
Michelle M
MM
McCubrey
James A
JA
Franklin
Richard A
RA
D000595:Amino Acid Sequence; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein; D015536:Down-Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019169:Jurkat Cells; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors; D012694:Serine / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D018106:CD28 Antigens; D017252:CD3 Complex; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D007093:Imidazoles; D007211:Indoles; D011725:Pyridines; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D012694:Serine; D006861:Hydrogen Peroxide; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C064758:Ro 31-8220