CaMKII mediates myocardial ischemia/reperfusion injuryinduced contracture in isolated rat heart.
Mol Med Rep
; 2019 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-31432114
Contracture or diastolic dysfunction is a primary cause of injury following ischemia/reperfusion (IR). The present study examined whether Ca2+/calmodulindependent 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 enddiastolic 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 KN62, an inhibitor of CaMKII, or 5 µM KBR7943, an inhibitor of the Na+/Ca2+ exchanger, mitigated the damage and the posttranslational modification of both CaMKII and PLN. Similar to the effect of the negative inotropic agent 2,3butanedionemonoxime, the increased cell survival after treatment with KN62 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 KN62 or KBR7943. Taken together, these data provided evidence that CaMKII mediates reperfusionelicited contracture, and that the activation of CaMKII via phosphorylation is involved in this process.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2019
Tipo de documento:
Article