Mechanism of telomerase induction during T cell activation.
The progressive shortening of the ends of chromosomes (telomeres) during cell division may serve as a mitotic clock for replicative senescence. Telomerase, a ribonucleoprotein which synthesizes telomeric DNA and maintains telomere length, is absent from most normal somatic cells but is expressed in immortal cells. Low levels of telomerase activity have been detected in peripheral blood mononuclear cells (PBMC) and hematopoietic cells and an increase in telomerase activity during T cell activation has recently been reported. In this study, we show that the increase in telomerase activity during T cell activation was transient and did not prevent the loss of telomeres in long-term T cell cultures. Analysis of the mechanism of telomerase induction showed that the increase in telomerase activity was accompanied by an increase in the levels of hTR, the RNA component of human telomerase. Moreover, telomerase induction occurred in the presence of aphidicolin, indicating that DNA synthesis was not required. Increased telomerase expression was observed when PBMC were activated with phorbol myristate acetate (PMA) and ionomycin, indicating that it was independent of early transmembrane signals. It was, however, linked to the T cell signal transduction pathway, as inhibiting protein kinase C with bisindolylmaleimide prevented the increase in telomerase activity.
Geron Corporation, Menlo Park, California 94025, USA.
A G
AG
Bodnar
N W
NW
Kim
R B
RB
Effros
C P
CP
Chiu
D000328:Adult; D016590:Aphidicolin / Q000494:pharmacology; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008301:Maleimides / Q000494:pharmacology; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017931:DNA Primers; D004791:Enzyme Inhibitors; D007211:Indoles; D007476:Ionophores; D008301:Maleimides; D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin; D015759:Ionomycin; D004247:DNA; D011493:Protein Kinase C; D019098:Telomerase; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate