Age-related decline in activation of calcium/calmodulin-dependent phosphatase calcineurin and kinase CaMK-IV in rat T cells.
We have previously shown that the DNA binding activity of the transcription factor NFAT which plays a predominant role in IL-2 transcription decreases with age. Because the transactivation (dephosphorylation and nuclear translocation) of the NFAT-c (cytoplasmic component of the NFAT complex) is mediated by the calcium/calmodulin-dependent phosphatase, calcineurin (CaN), and because Ca2+/calmodulin-dependent kinases (CaMK-II and IV/Gr) have been shown to play a critical role in calcium signaling in T cells, it was of interest to determine what effect aging has on the activation and the levels of these calcium regulating enzymes. The induction of calcineurin phosphatase activity, and CaMK-II and IV/Gr activities, were studied in splenic T cells isolated from Fischer 344 rats at 6, 15, and 24 months of age. In addition, the changes in the protein levels of these enzymes were measured by Western blot. The calcineurin phosphatase activity and CaMK-II and IV kinase activities were at a maximum after the cells were incubated with anti-CD3 antibody for 5-10 minutes. The induction of calcineurin activity by anti-CD3 and by calcium ionophore (A23187) declined 65 and 55%, respectively, between 6 and 24 months of age. The induction of CaMK-IV activity, but not CaMK-II activity by anti-CD3, was significantly less (by 54%) in T cells from old rats compared to T cells from young rats. The decline in the activation of these enzymes with age was not associated with changes in their corresponding protein levels. These results demonstrate that alterations in calcineurin phosphatase activity and CaMK-IV activity may contribute to the well-documented age-related decline in T cell function.
Pahlavani
M A
MA
Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, Audie L. Murphy Veterans Hospital, San Antonio 78284, USA. pahlavani@uthscsa.edu
Vargas
D M
DM
D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000001:Calcimycin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517686:Camk4 protein, rat; C120817:calcineurin phosphatase; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium