Oxidative activation of Ca2+/calmodulin-activated kinase II mediates ER stress-induced cardiac dysfunction and apoptosis
| العنوان: | Oxidative activation of Ca2+/calmodulin-activated kinase II mediates ER stress-induced cardiac dysfunction and apoptosis |
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| المؤلفون: | Nathan D. Roe, Jun Ren |
| المصدر: | American Journal of Physiology-Heart and Circulatory Physiology. 304:H828-H839 |
| بيانات النشر: | American Physiological Society, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Physiology, Apoptosis, Mice, Transgenic, medicine.disease_cause, Antioxidants, Mice, chemistry.chemical_compound, Physiology (medical), Internal medicine, Ca2+/calmodulin-dependent protein kinase, medicine, Animals, Myocytes, Cardiac, Calcium Signaling, chemistry.chemical_classification, Reactive oxygen species, NADPH oxidase, Ventricular Remodeling, biology, Tunicamycin, Endoplasmic reticulum, NADPH Oxidases, Heart, Stroke Volume, Catalase, Endoplasmic Reticulum Stress, Myocardial Contraction, Anti-Bacterial Agents, Endocrinology, chemistry, Echocardiography, cardiovascular system, Unfolded protein response, biology.protein, Signaling and Stress Response, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, Biomarkers, Oxidative stress |
| الوصف: | Endoplasmic reticulum (ER) stress elicits oxidative stress and intracellular Ca2+ derangement via activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). This study was designed to examine the role of CaMKII in ER stress-induced cardiac dysfunction and apoptosis as well as the effect of antioxidant catalase. Wild-type FVB and transgenic mice with cardiac-specific overexpression of catalase were challenged with the ER stress inducer tunicamycin (3 mg/kg ip for 48 h). Presence of ER stress was verified using the ER stress protein markers immunoglobulin binding protein (BiP) and C/EBP homologous protein (CHOP), the effect of which was unaffected by catalase overexpression. Echocardiographic assessment revealed that tunicamycin elicited cardiac remodeling (enlarged end-systolic diameter without affecting diastolic and ventricular wall thickness), depressed fractional shortening, ejection fraction, and cardiomyocyte contractile capacity, intracellular Ca2+ mishandling, accumulation of reactive oxygen species (superoxide production and NADPH oxidase p47phox level), CaMKII oxidation, and apoptosis (evidenced by Bax, Bcl-2/Bax ratio, and TUNEL staining), the effects of which were obliterated by catalase. Interestingly, tunicamycin-induced cardiomyocyte mechanical anomalies and cell death were ablated by the CaMKII inhibitor KN93, in a manner reminiscent of catalase. These data favored a permissive role of oxidative stress and CaMKII activation in ER stress-induced cardiac dysfunction and cell death. Our data further revealed the therapeutic potential of antioxidant or CaMKII inhibition in cardiac pathological conditions associated with ER stress. This research shows for the first time that contractile dysfunction caused by ER stress is a result of the oxidative activation of the CaMKII pathway. |
| تدمد: | 1522-1539 0363-6135 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c2070c21852f8d0d8986146ff07accb https://doi.org/10.1152/ajpheart.00752.2012 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1c2070c21852f8d0d8986146ff07accb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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