| First Author | Wang J | Year | 2021 |
| Journal | J Mol Cell Cardiol | Volume | 152 |
| Pages | 69-79 | PubMed ID | 33307093 |
| Mgi Jnum | J:308887 | Mgi Id | MGI:6753331 |
| Doi | 10.1016/j.yjmcc.2020.12.002 | Citation | Wang J, et al. (2021) Downregulation of the zinc transporter SLC39A13 (ZIP13) is responsible for the activation of CaMKII at reperfusion and leads to myocardial ischemia/reperfusion injury in mouse hearts. J Mol Cell Cardiol 152:69-79 |
| abstractText | While Zn(2+) dyshomeostasis is known to contribute to ischemia/reperfusion (I/R) injury, the roles of zinc transporters that are responsible for Zn(2+) homeostasis in the pathogenesis of I/R injury remain to be addressed. This study reports that ZIP13 (SLC39A13), a zinc transporter, plays a role in myocardial I/R injury by modulating the Ca(2+) signaling pathway rather than by regulating Zn(2+) transport. ZIP13 is downregulated upon reperfusion in mouse hearts or in H9c2 cells at reoxygenation. Ca(2+) but not Zn(2+) was responsible for ZIP13 downregulation, implying that ZIP13 may play a role in I/R injury through the Ca(2+) signaling pathway. In line with our assumption, knockout of ZIP13 resulted in phosphorylation (Thr(287)) of Ca(2+)-calmodulin-dependent protein kinase (CaMKII), indicating that downregulation of ZIP13 leads to CaMKII activation. Further studies showed that the heart-specific knockout of ZIP13 enhanced I/R-induced CaMKII phosphorylation in mouse hearts. In contrast, overexpression of ZIP13 suppressed I/R-induced CaMKII phosphorylation. Moreover, the heart-specific knockout of ZIP13 exacerbated myocardial infarction in mouse hearts subjected to I/R, whereas overexpression of ZIP13 reduced infarct size. In addition, knockout of ZIP13 induced increases of mitochondrial Ca(2+), ROS, mitochondrial swelling, decrease in the mitochondrial respiration control rate (RCR), and dissipation of mitochondrial membrane potential (DeltaPsim) in a CaMKII-dependent manner. These data suggest that downregulation of ZIP13 at reperfusion contributes to myocardial I/R injury through activation of CaMKII and the mitochondrial death pathway. |
