Age-related changes of proliferative response, kinetics of expression of protooncogenes after the mitogenic stimulation and methylation level of the protooncogene in purified human lymphocyte subsets.
Proliferative responses of highly purified T and B cells from aged persons to the combined stimulation with ionomycin and PMA were more significantly reduced than that from young ones although the degree of the age-related reduction was more significant in T cells than in B cells. In B cells, the levels and kinetics of c-myc gene expression after the stimulation were comparable between aged and young groups. In T cells, the maximum level of c-myc gene expression after the stimulation was comparable between the two age groups but the rate of reduction of c-myc mRNA was significantly retarded in the aged. The results of nuclear run on transcription assay showed the reduction of the rate of c-myc mRNA degradation seemed to be the cause. The levels and kinetics of c-myb gene expression in either T or B cells were comparable between the two age groups. We further examined the level of methylation of Xho I site of c-myc gene. The level of the methylation was significantly lower in the aged T cells and more significant in aged CD 8 positive T cells although that in aged B cells was comparable to that in young ones. The relation between a reduced proliferation, a retarded rate of c-myc mRNA degradation and reduction of methylation level of c-myc gene was discussed.
Deguchi
Y
Y
Third Department of Internal Medicine, Osaka University Hospital, Japan.
Negoro
S
S
Hara
H
H
Nishio
S
S
Kishimoto
S
S
D000375:Aging; D001402:B-Lymphocytes / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin; D008745:Methylation; D009857:Oncogenes; D011519:Proto-Oncogenes; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D004987:Ethers; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate