CaMKII mediates myocardial ischemia/reperfusion injury‑induced contracture in isolated rat heart
| Autor: | Jun Yu, Feng‑Mei Xiong, Ling‑Heng Kong, Jing‑Jun Zhou, Na Sun, Xing‑Li Su |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Necrosis Ischemia Biochemistry 03 medical and health sciences 0302 clinical medicine Internal medicine Ca2+/calmodulin-dependent protein kinase Genetics medicine Molecular Biology Chemistry musculoskeletal system medicine.disease Phospholamban 030104 developmental biology Endocrinology Oncology Apoptosis 030220 oncology & carcinogenesis cardiovascular system Molecular Medicine Phosphorylation medicine.symptom Contracture Reperfusion injury |
| Zdroj: | Molecular medicine reports. |
| ISSN: | 1791-3004 |
| Popis: | Contracture or diastolic dysfunction is a primary cause of injury following ischemia/reperfusion (IR). The present study examined whether Ca2+/calmodulin‑dependent kinase II (CaMKII) is involved in contracture. Isolated rat hearts were subjected to either global IR or Ca2+ paradox (CaP), which is characterized by contracture. Left ventricular end‑diastolic pressure, electron microscopy and troponin I TnI) in coronary effluent were examined to indicate the extent of contracture. Compared with control hearts, both the IR and CaP groups exhibited an increase in necrosis and apoptosis, and a marked depression in contractile function. Western blot analysis showed that IR stimulated the phosphorylation (Thr287) and oxidation (Met281/282) of CaMKII, and the phosphorylation of phospholamban (PLN), a substrate of CaMKII. By contrast, only the phosphorylation of CaMKII was increased in the CaP group. Treatment with either 3 µM KN‑62, an inhibitor of CaMKII, or 5 µM KB‑R7943, an inhibitor of the Na+/Ca2+ exchanger, mitigated the damage and the post‑translational modification of both CaMKII and PLN. Similar to the effect of the negative inotropic agent 2,3‑butanedione‑monoxime, the increased cell survival after treatment with KN‑62 was associated with improved diastolic function. Examination using electron microscopy and a biochemical test showed the development of contraction bands, disruption of the sarcolemmal membrane and an increase in the release of TnI in both IR and CaP hearts; these results indicated the occurrence of contracture. Furthermore, these changes were inhibited by either KN‑62 or KB‑R7943. Taken together, these data provided evidence that CaMKII mediates reperfusion‑elicited contracture, and that the activation of CaMKII via phosphorylation is involved in this process. |
| Databáze: | OpenAIRE |
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