| First Author | Wu Y | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 9291 |
| PubMed ID | 31243295 | Mgi Jnum | J:279869 |
| Mgi Id | MGI:6357504 | Doi | 10.1038/s41598-019-45743-6 |
| Citation | Wu Y, et al. (2019) Myocardial death and dysfunction after ischemia-reperfusion injury require CaMKIIdelta oxidation. Sci Rep 9(1):9291 |
| abstractText | Reactive oxygen species (ROS) contribute to myocardial death during ischemia-reperfusion (I/R) injury, but detailed knowledge of molecular pathways connecting ROS to cardiac injury is lacking. Activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIdelta) is implicated in myocardial death, and CaMKII can be activated by ROS (ox-CaMKII) through oxidation of regulatory domain methionines (Met281/282). We examined I/R injury in mice where CaMKIIdelta was made resistant to ROS activation by knock-in replacement of regulatory domain methionines with valines (MMVV). We found reduced myocardial death, and improved left ventricular function 24 hours after I/R injury in MMVV in vivo and in vitro compared to WT controls. Loss of ATP sensitive K(+) channel (KATP) current contributes to I/R injury, and CaMKII promotes sequestration of KATP from myocardial cell membranes. KATP current density was significantly reduced by H2O2 in WT ventricular myocytes, but not in MMVV, showing ox-CaMKII decreases KATP availability. Taken together, these findings support a view that ox-CaMKII and KATP are components of a signaling axis promoting I/R injury by ROS. |
