Aging reduces glycerol-3-phosphate acyltransferase activity in activated rat splenic T-lymphocytes.
T-lymphocyte proliferation declines with age. Phosphatidic acid (PA) is the precursor to all glycerophospholipids, which serve as important membrane structural components and signaling molecules. Therefore, we tested the hypothesis that aged T-lymphocyte proliferation may be reduced, in part, suppressing phosphatidic acid (PA) biosynthesis. We showed, for the first time, that anti-CD3 stimulation in rat splenic T-lymphocytes selectively increased mitochondrial glycerol-3-phosphate acyltransferase (GPAT) activity. GPAT activity could be further increased by the addition of recombinant acyl-CoA binding protein (rACBP), but the amplification of GPAT activity was blunted by aging. This is important because PA is the precursor lipid for phospholipid synthesis and GPAT is the rate-limiting enzyme in PA biosynthesis. The mechanism by which stimulation and rACBP increased GPAT activity may involve phosphorylation since incubating Jurkat T-lymphocyte mitochondria with casein kinase 2 in vitro significantly increased GPAT activity. The data presented here suggest a novel mechanism by which aging may reduce activation-dependent mitochondrial GPAT activity. This age-induced alteration would result in reduced PA biosynthesis and could explain, in part, the diminished phospholipid content of the membrane and subsequent loss of proliferative capacity in the aged T-lymphocyte.
Collison
Lauren W
LW
Division of Nutritional Sciences and the Institute for Cellular and Molecular Biology, The University of Texas at Austin, 1 University Station A2700, Austin, TX 78712, USA.
Kannan
Latha
L
Onorato
Thomas M
TM
Knudsen
Jens
J
Haldar
Dipak
D
Jolly
Christopher A
CA
D000375:Aging / Q000502:physiology*; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology
D017252:CD3 Complex; D010712:Phosphatidic Acids; D005992:Glycerol-3-Phosphate O-Acyltransferase; D047390:Casein Kinase II