Ischemic postconditioning protects the heart against ischemia-reperfusion injury via neuronal nitric oxide synthase in the sarcoplasmic reticulum and mitochondria
| Autor: | Quanpeng Li, Wu Xiaolu, Li Zhou, Maojuan Hao, Liu-Qing Hu, Chang Liu, Y Wang, Jue-Jin Wang, Hua-Yuan Zhu, Suhua Zhu, Yi Fan, Yi-Chen Song |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Cancer Research Myocardial Infarction Nitric Oxide Synthase Type I 030204 cardiovascular system & hematology Mitochondrion AMP-Activated Protein Kinases medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Mice 0302 clinical medicine Myocyte Myocytes Cardiac Enzyme Inhibitors Phosphorylation Ischemic Postconditioning Nitrotyrosine musculoskeletal system Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Phospholamban Mitochondria Sarcoplasmic Reticulum cardiovascular system Original Article inorganic chemicals medicine.medical_specialty Immunology Primary Cell Culture Myocardial Reperfusion Injury Biology Cell Line Superoxide dismutase 03 medical and health sciences Cellular and Molecular Neuroscience Organ Culture Techniques Internal medicine medicine Animals Arginase Myocardium Calcium-Binding Proteins AMPK Cell Biology medicine.disease Rats Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry nervous system Animals Newborn Gene Expression Regulation biology.protein Calcium Reperfusion injury Oxidative stress |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | As a result of its spatial confinement in cardiomyocytes, neuronal nitric oxide synthase (nNOS) is thought to regulate mitochondrial and sarcoplasmic reticulum (SR) function by maintaining nitroso-redox balance and Ca2+ cycling. Thus, we hypothesize that ischemic postconditioning (IPostC) protects hearts against ischemic/reperfusion (I/R) injury through an nNOS-mediated pathway. Isolated mouse hearts were subjected to I/R injury in a Langendorff apparatus, H9C2 cells and primary neonatal rat cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, decreased infarct size and improved cardiac function, and the selective nNOS inhibitors abolished these effects. IPostC recovered nNOS activity and arginase expression. IPostC also increased AMP kinase (AMPK) phosphorylation and alleviated oxidative stress, and nNOS and AMPK inhibition abolished these effects. IPostC increased nitrotyrosine production in the cytosol but decreased it in mitochondria. Enhanced phospholamban (PLB) phosphorylation, normalized SR function and decreased Ca2+ overload were observed following the recovery of nNOS activity, and nNOS inhibition abolished these effects. Similar effects of IPostC were demonstrated in cardiomyocytes in vitro. IPostC decreased oxidative stress partially by regulating uncoupled nNOS and the nNOS/AMPK/peroxisome proliferator-activated receptor gamma coactivator 1 alpha/superoxide dismutase axis, and improved SR function through increasing SR Ca2+ load. These results suggest that IPostC protected hearts against I/R injury via an nNOS-mediated pathway. |
| Databáze: | OpenAIRE |
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