期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1761, 期 1, 页码 129-139出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2005.12.002
关键词
aging; T-lymphocyte; phosphatidic acid; acyltransferase; protein kinase C
Recently, we have shown that stimulation and recombinant ACBP increase mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT) activity in rat splenic T-lymphocytes and that this effect is blunted in aged T-lymphocytes. In addition to decreased mtGPAT activity, aged T-lymphocytes also have altered membrane lipid composition and decreased proliferation in response to antigen. Therefore, we wanted to determine the mechanism by which mtGPAT activity is regulated in aged T-lymphocytes. We show that aged T-lymphocyte mtGPAT activity is not increased by ex vivo stimulation or in vitro phosphorylation with casein kinase II and protein kinase C theta as is seen in Young T-lymphocytes. However, other factors that might impact mtGPAT activity such as reduced mtGPAT protein levels, gene expression or alterations in the soluble acyl-CoA pool were not affected by age or stimulation. The age effect was also not compensated for by increased acyl-CoA binding protein expression in aged T-lymphocytes. Currently, two mitochondrial GPAT (mtGPAT) isoforms (mtGPAT1 and mtGPAT2) have been identified. We found that T-lymphocytes express rntGPAT1, but not mtGPAT2, suggesting that at least mtGPAT1 is sensitive to phosphorylation in vitro. Support for direct phosphorylation of mtGPAT1 in young T-lymphocytes is shown by mtGPAT1 immunoprecipitation where a phosphoprotein band was detected migrating at the same molecular weight (85 kDa) as mtGPAT1. This is significant because we also show that T-lymphocytes from mtGPAT1 KO mice have reduced proliferation ex vivo as is seen in aged T-lymphocytes. These data provide evidence for a novel mechanism by which T-lymphocyte proliferation may be regulated and, for the first time, give a potential mechanistic explanation for the correlation between reduced proliferation and membrane lipid changes seen in aged T-lymphocytes. (c) 2005 Elsevier B.V. All rights reserved.
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