Reduced activation of transcriptional factor AP-1 among peripheral blood T cells from elderly humans after PHA stimulation: restorative effect of phorbol diesters.
In the present study, we evaluated if aging influences the activation and characteristics of transcriptional factor AP-1 in human T cells. Using gel mobility shift assays, the activation of AP-1 was quantified in peripheral blood T cells from 11 elderly (mean 74 year) and young (mean 33 year) subjects following stimulation with PHA, PMA, or PHA plus PMA. The results showed that the activation of AP-1 was significantly reduced in PHA-stimulated T cells from the group of elderly subjects when compared to T cells from young subjects (P < 0.05). Even though PHA-stimulated T cells from 8 of the elderly subjects had pronounced impairments in the activation of AP-1, additional signals provided by costimulation with PMA frequently restored AP-1 activation to more normal levels. Other experiments demonstrated that the AP-1 complexes expressed by stimulated T cells of elderly and young subjects exhibited similar properties in gel shift assays with competing unlabeled AP-1 oligonucleotides and with blocking antibodies specific for Fos and Jun. Thus, these data suggest that the activation of AP-1 can be reduced in human T cells during aging and that these reductions may often be related to impairments in signal transduction rather than represent an absolute loss in the ability to express AP-1.
Whisler
R L
RL
Department of Medical Biochemistry, William H. Davis Medical Research Center, Ohio State University, Columbus 43210-1228.
Liu
B
B
Wu
L C
LC
Chen
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000595:Amino Acid Sequence; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification; D010835:Phytohemagglutinins / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D016755:Proto-Oncogene Proteins c-jun; D013755:Tetradecanoylphorbol Acetate