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Journal article
The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations
Scientific reports, Vol.8(1), pp.6289-9
19 Apr 2018
PMCID: PMC5908836
PMID: 29674640
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Etomoxir (ETO) is a widely used small-molecule inhibitor of fatty acid oxidation (FAO) through its irreversible inhibitory effects on the carnitine palmitoyl-transferase la (CPT1a). We used this compound to evaluate the role of fatty acid oxidation in rapidly proliferating T cells following costimulation through the CD28 receptor. We show that ETO has a moderate effect on T cell proliferation with no observable effect on memory differentiation, but a marked effect on oxidative metabolism. We show that this oxidative metabolism is primarily dependent upon glutamine rather than FAO. Using an shRNA approach to reduce CPT1a in T cells, we further demonstrate that the inhibition of oxidative metabolism in T cells by ETO is independent of its effects on FAO at concentrations exceeding 5 mu M. Concentrations of ETO above 5 mu M induce acute production of ROS with associated evidence of severe oxidative stress in proliferating T cells. In aggregate, these data indicate that ETO lacks specificity for CTP1a above 5 mu M, and caution should be used when employing this compound for studies in cells due to its non-specific effects on oxidative metabolism and cellular redox.
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Details
- Title
- The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations
- Creators
- Roddy S. O'Connor - Univ Penn, Ctr Cellular Immunotherapies, Perelman Sch Med, Philadelphia, PA 19104 USALili Guo - Translational TherapeuticsSaba Ghassemi - University of PennsylvaniaNathaniel W. Snyder - Drexel UniversityAndrew J. Worth - Translational TherapeuticsLiwei Weng - Translational TherapeuticsYoonseok Kam - Agilent TechnologiesBenjamin Philipson - University of PennsylvaniaSophie Trefely - Drexel UniversitySelene Nunez-Cruz - University of PennsylvaniaIan A. Blair - Translational TherapeuticsCarl H. June - University of PennsylvaniaMichael C. Milone - University of Pennsylvania
- Publication Details
- Scientific reports, Vol.8(1), pp.6289-9
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- University of Pennsylvania-Novartis Alliance R21HD087866 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) P30ES013508; P30CAO16520; K22ES026235; R21HD087866 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA K22ES026235 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Identifiers
- 991019167623404721
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- Web of Science research areas
- Immunology