Journal article
Mitochondrial Glycerol-3-Phosphate Acyltransferase-Dependent Phospholipid Synthesis Modulates Phospholipid Mass and IL-2 Production in Jurkat T Cells
Lipids, Vol.51(3), pp.291-301
03/2016
DOI: 10.1007/s11745-016-4121-5
PMID: 26797755
Abstract
Changes in glycerophospholipid metabolism with age and disease can have a profound effect on immune cell activation and effector function. We previously demonstrated that glycerol-3-phosphate acyltransferase-1, the first and rate limiting step in de novo glycerophospholipid synthesis, plays a role in modulating murine T cell function. The resultant phenotype is characterized by decreased IL-2 production, increased propensity toward apoptosis, and altered membrane glycerophospholipid mass similar to that of an aged T cell. Since T cells in previous experiments were harvested from GPAT-1(-/-) mice, questions remained as to what extent the macro environment of the model influenced the observed cellular phenotype. Therefore, we generated and phenotypically characterized a mitochondrial glycerol-3-phosphate acyltransferase (GPAM) deficient Jurkat T cell. Furthermore, this line was used to probe possible mechanisms by which GPAT-1/GPAM regulates T cell function. We report here that many of the key dysfunctional characteristics of murine GPAT-1(-/-) T cells are recapitulated in the GPAMKD Jurkat T cell. We found striking decreased IL-2 production along with altered phospholipid mass and increased incidence of apoptosis. Since PtdOH is an indirect downstream product of GPAM, we attempted to rescue IL-2 production with PtdOH supplementation; however, this addition did not return IL-2 production to normal levels. Interestingly, we did find significantly decreased Zap-70 phosphorylation following stimulation, suggesting that GPAM deficiency may alter membrane based stimulatory signaling. These data show for the first time that GPAM deficiency results in an inherent defect in Jurkat T cell function and glycerophospholipid composition and that this defect cannot be rescued by addition of exogenous PtdOH.
Details
- Title: Subtitle
- Mitochondrial Glycerol-3-Phosphate Acyltransferase-Dependent Phospholipid Synthesis Modulates Phospholipid Mass and IL-2 Production in Jurkat T Cells
- Creators
- Robert Faris - Department of Nutritional Sciences, College of Natural Sciences, Austin, TX, USAMary M Weber - Laboratory of Bacteriology, National Institutes of Health, Hamilton, MT, USADrew R Seeger - University of North Dakota, Pharmacology, Physiology, and Therapeutics, Grand Forks, ND, USADavid Cavazos - Department of Nutritional Sciences, College of Natural Sciences, Austin, TX, USALinda de Graffenried - Department of Nutritional Sciences, College of Natural Sciences, Austin, TX, USAEric J Murphy - University of North Dakota, Pharmacology, Physiology, and Therapeutics, Grand Forks, ND, USAChristopher A Jolly - Department of Nutritional Sciences, College of Natural Sciences, Austin, TX, USA. jolly@austin.utexas.edu
- Resource Type
- Journal article
- Publication Details
- Lipids, Vol.51(3), pp.291-301
- DOI
- 10.1007/s11745-016-4121-5
- PMID
- 26797755
- ISSN
- 0024-4201
- eISSN
- 1558-9307
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984083872302771
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