دورية أكاديمية
أعرض في EDS

Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.

التفاصيل البيبلوغرافية
العنوان: Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.
المؤلفون: Conklin DJ; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.). dj.conklin@louisville.edu., Guo Y; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Jagatheesan G; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Kilfoil PJ; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Haberzettl P; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Hill BG; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Baba SP; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Guo L; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Wetzelberger K; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Obal D; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Rokosh DG; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Prough RA; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Prabhu SD; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Velayutham M; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Zweier JL; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Hoetker JD; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Riggs DW; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Srivastava S; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Bolli R; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.)., Bhatnagar A; From the Diabetes and Obesity Center (D.J.C., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., K.W., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B.), Institute of Molecular Cardiology (D.J.C., Y.G., P.J.K., P.H., B.G.H., S.P.B., D.O., D.G.R., S.S., R.B., A.B.), Division of Cardiovascular Medicine, Department of Medicine (D.J.C., Y.G., G.J., P.J.K., P.H., B.G.H., S.P.B., L.G., D.O., D.G.R., J.D.H., D.W.R., S.S., R.B., A.B), Department of Anesthesiology and Perioperative Medicine (D.O.), and Department of Biochemistry and Molecular Genetics (P.J.K., R.A.P., A.B.), University of Louisville, KY; Division of Cardiovascular Disease, University of Alabama at Birmingham (S.D.P.); and Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (M.V., J.L.Z.).
المصدر: Circulation research [Circ Res] 2015 Aug 14; Vol. 117 (5), pp. 437-49. Date of Electronic Publication: 2015 Jul 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.
مواضيع طبية MeSH: Glutathione Transferase/*deficiency , Glutathione Transferase/*genetics , Myocardial Reperfusion Injury/*enzymology , Myocardial Reperfusion Injury/*genetics , Myocardium/*metabolism, Animals ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardial Reperfusion Injury/pathology ; Myocardium/pathology
مستخلص: Rationale: Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed.
Objective: We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury.
Methods and Results: In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1, and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism of 4-hydroxy-trans-2-nonenal or trans-2-hexanal; on ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than wild-type hearts. GSTP deficiency did not affect I/R-induced free radical generation, c-Jun N-terminal kinase activation, or depletion of reduced glutathione. Acrolein exposure induced a hyperpolarizing shift in INa, and acrolein-induced cell death was delayed by SN-6, a Na(+)/Ca(++) exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than wild-type myocytes to acrolein-induced protein crosslinking and cell death.
Conclusions: GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes, such as acrolein.
(© 2015 American Heart Association, Inc.)
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معلومات مُعتمدة: HL78825 United States HL NHLBI NIH HHS; GM103492 United States GM NIGMS NIH HHS; R01 HL059378 United States HL NHLBI NIH HHS; ES14559 United States ES NIEHS NIH HHS; R01 HL089380 United States HL NHLBI NIH HHS; HL89380 United States HL NHLBI NIH HHS; HL55477 United States HL NHLBI NIH HHS; T35 ES014559 United States ES NIEHS NIH HHS; P20 GM103492 United States GM NIGMS NIH HHS; P01 HL078825 United States HL NHLBI NIH HHS; HL99014 United States HL NHLBI NIH HHS; R01 HL130174 United States HL NHLBI NIH HHS; R01 HL055477 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: acrolein; glutathione transferase; lipid peroxidation; myocardial infarction; myocardial ischemia; oxidative stress; reperfusion injury
المشرفين على المادة: EC 2.5.1.18 (Glutathione Transferase)
تواريخ الأحداث: Date Created: 20150715 Date Completed: 20151030 Latest Revision: 20190206
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4854443
DOI: 10.1161/CIRCRESAHA.114.305518
PMID: 26169370
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4571
DOI:10.1161/CIRCRESAHA.114.305518