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Kong LH, Xiong FM, Su XL, et al. CaMKII mediates myocardial ischemia/reperfusion injury‑induced contracture in isolated rat heart. Mol Med Rep. 2019;doi: 10.3892/mmr.2019.10550.
Kong, L. H., Xiong, F. M., Su, X. L., Sun, N., Zhou, J. J., & Yu, J. (2019). CaMKII mediates myocardial ischemia/reperfusion injury‑induced contracture in isolated rat heart. Molecular medicine reports, . https://doi.org/10.3892/mmr.2019.10550
Kong, Ling-Heng, et al. "CaMKII mediates myocardial ischemia/reperfusion injury‑induced contracture in isolated rat heart." Molecular medicine reports vol. (2019). doi: https://doi.org/10.3892/mmr.2019.10550
Kong LH, Xiong FM, Su XL, Sun N, Zhou JJ, Yu J. CaMKII mediates myocardial ischemia/reperfusion injury‑induced contracture in isolated rat heart. Mol Med Rep. 2019 Aug 01; doi: 10.3892/mmr.2019.10550. Epub 2019 Aug 01. PMID: 31432114.
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Mol Med Rep. 2019 Aug 01; doi: 10.3892/mmr.2019.10550. Epub 2019 Aug 01.

CaMKII mediates myocardial ischemia/reperfusion injury‑induced contracture in isolated rat heart.

Molecular medicine reports

Ling-Heng Kong, Feng-Mei Xiong, Xing-Li Su, Na Sun, Jing-Jun Zhou, Jun Yu

Affiliations

  1. Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
  2. Department of Pharmacy, Xi'an Children's Hospital, Xi'an, Shaanxi 710003, P.R. China.
  3. Institute of Basic Medical Science, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
  4. Department of Physiology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

PMID: 31432114 DOI: 10.3892/mmr.2019.10550

Abstract

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.

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