Retracted: Activation of Akt Rescues Endoplasmic Reticulum Stress-Impaired Murine Cardiac Contractile Function via Glycogen Synthase Kinase-3β-Mediated Suppression of Mitochondrial Permeation Pore Opening
| العنوان: | Retracted: Activation of Akt Rescues Endoplasmic Reticulum Stress-Impaired Murine Cardiac Contractile Function via Glycogen Synthase Kinase-3β-Mediated Suppression of Mitochondrial Permeation Pore Opening |
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| المؤلفون: | Zhi Xia, Yingmei Zhang, Karissa H. La Cour, Jun Ren |
| المصدر: | Antioxidants & Redox Signaling. 15:2407-2424 |
| بيانات النشر: | Mary Ann Liebert Inc, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Cell Survival, Physiology, Clinical Biochemistry, Mice, Transgenic, Mitochondrion, Mitochondrial Membrane Transport Proteins, Biochemistry, Glycogen Synthase Kinase 3, Mice, chemistry.chemical_compound, Mitochondrial membrane transport protein, GSK-3, Animals, Myocytes, Cardiac, Enzyme Inhibitors, Cell Shape, Endoplasmic Reticulum Chaperone BiP, Molecular Biology, Protein kinase B, Cells, Cultured, General Environmental Science, Membrane Potential, Mitochondrial, biology, Mitochondrial Permeability Transition Pore, Endoplasmic reticulum, Cell Biology, Tunicamycin, Endoplasmic Reticulum Stress, Myocardial Contraction, Molecular biology, Mitochondria, Cell biology, Original Research Communications, Mitochondrial permeability transition pore, chemistry, Echocardiography, biology.protein, Unfolded protein response, General Earth and Planetary Sciences, Calcium, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt |
| الوصف: | The present study was designed to examine the impact of chronic Akt activation on endoplasmic reticulum (ER) stress-induced cardiac mechanical anomalies, if any, and the underlying mechanism involved.Wild-type and transgenic mice with cardiac-specific overexpression of the active mutant of Akt (Myr-Akt) were subjected to the ER stress inducer tunicamycin (1 or 3 mg/kg). ER stress led to compromised echocardiographic (elevated left ventricular end-systolic diameter and reduced fractional shortening) and cardiomyocyte contractile function, intracellular Ca(2+) mishandling, and cell survival in wild-type mice associated with mitochondrial damage. In vitro ER stress induction in murine cardiomyocytes upregulated the ER stress proteins Gadd153, GRP78, and phospho-eIF2α, and promoted reactive oxygen species production, carbonyl formation, apoptosis, mitochondrial membrane potential loss, and mitochondrial permeation pore (mPTP) opening associated with overtly impaired cardiomyocyte contractile and intracellular Ca(2+) properties. Interestingly, these anomalies were mitigated by chronic Akt activation or the ER chaperon tauroursodeoxycholic acid (TUDCA). Treatment with tunicamycin also dephosphorylated Akt and its downstream signal glycogen synthase kinase 3β (GSK3β) (leading to activation of GSK3β), the effect of which was abrogated by Akt activation and TUDCA. The ER stress-induced cardiomyocyte contractile and mitochondrial anomalies were obliterated by the mPTP inhibitor cyclosporin A, GSK3β inhibitor SB216763, and ER stress inhibitor TUDCA.This research reported the direct relationship between ER stress and cardiomyocyte contractile and mitochondrial anomalies for the first time.Taken together, these data suggest that ER stress may compromise cardiac contractile and intracellular Ca(2+) properties, possibly through the Akt/GSK3β-dependent impairment of mitochondrial integrity. |
| تدمد: | 1557-7716 1523-0864 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5147cc758d730414f7788241d1b49fc https://doi.org/10.1089/ars.2010.3751 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b5147cc758d730414f7788241d1b49fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577716 15230864 |
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