| First Author | Köhler D | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e98325 |
| PubMed ID | 24858945 | Mgi Jnum | J:216314 |
| Mgi Id | MGI:5608633 | Doi | 10.1371/journal.pone.0098325 |
| Citation | Kohler D, et al. (2014) Galphai2- and Galphai3-deficient mice display opposite severity of myocardial ischemia reperfusion injury. PLoS One 9(5):e98325 |
| abstractText | G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their alpha-subunit: Galphai, Galphas, Galphaq and G12/13. Galphai-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Galphai2 or Galphai3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Galphai2 and Galphai3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Galphai2-, and Galphai3-deficient mice. Galphai2 was expressed at higher levels than Galphai3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Galphai-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Galphai2 and Galphai3, indicating important roles for both Galphai isoforms. Furthermore, ischemia reperfusion injury in Galphai2- and Galphai3-deficient mice exhibited opposite outcomes. Whereas the absence of Galphai2 significantly increased the infarct size in the heart, the absence of Galphai3 or the concomitant upregulation of Galphai2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Galphai proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent. |
