The inhibition of calcium signaling in T lymphocytes from old mice results from enhanced activation of the mitochondrial permeability transition pore.
Aging attenuates calcium signaling in T lymphocytes from old mice. Aging also attenuates the sustained elevation of cell free calcium by ionomycin, which is similar to the T cell receptor signal. In T lymphocytes from young mice, the ionomycin-induced elevation of cell free calcium was inhibited by collapsing the mitochondrial membrane potential by uncouplers and ionophores, and activation of the permeability transition. In T lymphocytes from old mice, the mitochondrial membrane potential was largely collapsed, but cyclosporin and N-methyl-val-4-cyclosporin, inhibitors of the permeability transition, restored the mitochondrial potential, as well as the ionomycin-induced elevation of cell free calcium. In addition, the generation of reactive oxygen species in the presence of mitochondrial electron transport inhibitors was relatively enhanced in T lymphocytes from old mice. The association between low rhodamine 123 fluorescence and attenuated calcium signaling in T lymphocytes from old mice is also shown to be a consequence of the collapsed mitochondrial potential. These results suggest that Ca2+ signaling is attenuated in T lymphocytes from old mice because of an enhanced activation of the permeability transition.
Mather
Michael W
MW
Department of Microbiology and Immunology, MCP Hahnemann University School of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. michael.mather@drexel.edu
Rottenberg
Hagai
H
D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005456:Fluorescent Dyes; D007156:Immunologic Memory; D007425:Intracellular Membranes / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010084:Oxidation-Reduction; D020112:Rhodamine 123; D013154:Spleen / Q000166:cytology; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D005456:Fluorescent Dyes; D007473:Ion Channels; D007476:Ionophores; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013481:Superoxides; D005182:Flavin-Adenine Dinucleotide; D020112:Rhodamine 123; D015759:Ionomycin; D016572:Cyclosporine; D002118:Calcium