Long chain fatty acid utilization of T-cells from autoimmune MRL-lpr/lpr mice.
To test the hypothesis that T-cells which exhibit abnormal immunological behavior manifest derangements in the de novo synthesis of phospholipids, the utilization of [3H]palmitic acid in B220+ T-cells from autoimmune MRL-lpr/lpr mice was investigated. The rate of incorporation of [3H]palmitic acid into membrane phospholipids was markedly increased in intact B220+ T-cells compared to that in T-cells from immunologically normal mice. The activities of two key enzymes involved in the de novo synthesis of palmitoyl-phospholipids, acyl-coenzyme (CoA) ligase and acyl-CoA; sn-glycerol-3-phosphate acyl transferase, were significantly higher in homogenates from B220+ T-cell membranes compared with those in controls. Despite these findings, the molar concentration of individual palmitoyl glycerolipids was equivalent in the membranes of B220+ T-cells and control lymph node T-cells. The results indicate that T-cells from lupus mice exhibit complex defects in the biosynthesis and turnover of membrane phospholipids and suggest the possibility that these aberrations contribute to T-cell dysfunction in autoimmune diseases.
Ando
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Department of Medicine, University of Colorado Health Sciences Center, Denver.
Tomita-Yamaguchi
T
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Santoro
T J
TJ
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000378:metabolism; D015256:Coenzyme A-Transferases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000032:analysis / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000378:metabolism*; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013601:T-Lymphocytes / Q000378:metabolism*; D014316:Tritium; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D005227:Fatty Acids; D008563:Membrane Lipids; D010169:Palmitic Acids; D010743:Phospholipids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014316:Tritium; D010171:Palmitoyl Coenzyme A; D019308:Palmitic Acid; D015256:Coenzyme A-Transferases; C031212:acyl-CoA transferase; D010170:Palmitoyl-CoA Hydrolase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase