ArticleCirculation research2015
Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.
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Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
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- SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy.International journal of biological sciences · 2024Article
- Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure.Research square · 2023Article
- Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles.Antioxidants (Basel, Switzerland) · 2023Article
- MicroRNA-29b reduces myocardial ischemia-reperfusion injury in rats via down-regulating PTEN and activating the Akt/eNOS signaling pathway.Journal of thrombosis and thrombolysis · 2022Article
- Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction.Physiological reports · 2021Article
- Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion‑induced acute lung injury by inhibiting autophagy in diabetic rats.Molecular medicine reports · 2021Article
- Urinary Levels of the Acrolein Conjugates of Carnosine Are Associated with Cardiovascular Disease Risk.International journal of molecular sciences · 2021Observational
- Potential mechanism of action ofRSC advances · 2020Article
- S-glutathionylation, friend or foe in cardiovascular health and disease.Redox biology · 2020Review
- Cardiospecific Overexpression of ATPGD1 (Carnosine Synthase) Increases Histidine Dipeptide Levels and Prevents Myocardial Ischemia Reperfusion Injury.Journal of the American Heart Association · 2020Article
- Sulodexide up-regulates glutathione S-transferase P1 by enhancing Nrf2 expression and translocation in human umbilical vein endothelial cells injured by oxygen glucose deprivation.Archives of medical science : AMS · 2020Article
- Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation.Oxidative medicine and cellular longevity · 2020Article
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Authors and funding
20 authors at 2 institutions in 1 country.
Daniel J ConklinFrom 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.
Yiru GuoFrom 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.).
Ganapathy JagatheesanFrom 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.).
Peter J KilfoilFrom 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.).
Petra HaberzettlFrom 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.).
Bradford G HillFrom 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.).
Shahid P BabaFrom 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.).
Luping GuoFrom 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.).
Karin WetzelbergerFrom 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.).
Detlef ObalFrom 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.).
D Gregg RokoshFrom 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.).
Russell A ProughFrom 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.).
Sumanth D PrabhuFrom 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.).
Murugesan VelayuthamFrom 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.).
Jay L ZweierFrom 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.).
J David HoetkerFrom 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.).
Daniel W RiggsFrom 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.).
Sanjay SrivastavaFrom 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.).
Roberto BolliFrom 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.).
Aruni BhatnagarFrom 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.).
University of Alabama at Birmingham · USUniversity of Louisville · US
Funding
Tumor Necrosis Factor Modulation of CPCsP01HL078825 · NHLBI · UNIVERSITY OF LOUISVILLE · PI BOLLI, ROBERTO · 2005 to 2021
$37.6MProject 5 - Metabolomic Analysis of AtherothrombosisP20GM103492 · NIGMS · UNIVERSITY OF LOUISVILLE · PI DEFILIPPIS, ANDREW · 2012 to 2017
$13.8MTOXICITY OF 4-HYDROXYALKENALS IN HEARTR01HL055477 · NHLBI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI BHATNAGAR, ARUNI · 1997 to 2015
$4.4MCARDIAC METABOLISM OF ENALSR01HL059378 · NHLBI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI BHATNAGAR, ARUNI · 1998 to 2011
$3.3MCardioprotective Mechanisms of Glutathione S-transferase PR01HL089380 · NHLBI · UNIVERSITY OF LOUISVILLE · PI CONKLIN, DANIEL JOSEPH · 2008 to 2012
$2.1MMetabolic optimization of cell therapyR01HL130174 · NHLBI · UNIVERSITY OF LOUISVILLE · PI HILL, BRADFORD GUY · 2016 to 2020
$1.9MRole of Glutathione S-Transferase P in Heart FailureR01HL099014 · NHLBI · UNIVERSITY OF LOUISVILLE · PI PRABHU, SUMANTH D · 2010 to 2013
$1.5MSummer Environmental Health Sciences Training ProgramT35ES014559 · NIEHS · UNIVERSITY OF LOUISVILLE · PI Matthew C Cave, Daniel Joseph Conklin · 2006 to 2026
$751kNHLBI NIH HHS HL55477NHLBI NIH HHS HL78825NHLBI NIH HHS HL89380NHLBI NIH HHS HL99014NHLBI NIH HHS P01 HL078825NHLBI NIH HHS R01 HL055477NHLBI NIH HHS R01 HL059378NHLBI NIH HHS R01 HL089380NHLBI NIH HHS R01 HL130174NIEHS NIH HHS ES14559NIEHS NIH HHS T35 ES014559NIGMS NIH HHS GM103492NIGMS NIH HHS P20 GM103492
Abstract
rationaleMyocardial 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.
objectiveWe tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury. METHODS AND
resultsIn 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.
conclusionsGSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes, such as acrolein.
Indexed as
AnimalsGlutathione TransferaseMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial Reperfusion InjuryMyocardiumGlutathione Transferaseacroleinglutathione transferaselipid peroxidationmyocardial infarctionmyocardial ischemiaoxidative stressreperfusion injury
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