| First Author | Waterson RE | Year | 2011 |
| Journal | Cardiovasc Res | Volume | 91 |
| Issue | 1 | Pages | 45-52 |
| PubMed ID | 21349876 | Mgi Jnum | J:191634 |
| Mgi Id | MGI:5462185 | Doi | 10.1093/cvr/cvr054 |
| Citation | Waterson RE, et al. (2011) Galpha(i2)-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart. Cardiovasc Res 91(1):45-52 |
| abstractText | AIMS: Regulator of G protein signalling (RGS) proteins act as molecular 'off switches' that terminate G protein signalling by catalyzing the hydrolysis of Galpha-bound GTP to GDP. Many different Galpha(i)-coupled receptors have been implicated in the cardioprotective effects of ischaemic preconditioning. However, the role of RGS proteins in modulating cardioprotection has not been previously investigated. We used mice that were homozygous (GS/GS) or heterozygous (GS/+) for a mutation in Galpha(i2) rendering it RGS-insensitive (G184S) to determine whether interactions between endogenous RGS proteins and Galpha(i2) modulate Galpha(i)-mediated protection from ischaemic injury. METHODS AND RESULTS: Langendorff-perfused mouse hearts were subjected to 30 min global ischaemia and 2 h reperfusion. Infarcts in GS/GS (14.5% of area at risk) and GS/+ (22.6% of AAR) hearts were significantly smaller than those of +/+ hearts (37.2% of AAR) and recovery of contractile function was significantly enhanced in GS/GS and GS/+ hearts compared with +/+ hearts. The cardioprotective phenotype was not reversed by wortmannin or U0126 but was reversed by 5-hydroxydecanoic acid and HMR 1098, indicating that RGS-insensitive Galpha(i2) protects the heart through a mechanism that requires functional ATP-dependent potassium channels but does not require acute activation of extracellular-regulated kinase or Akt signalling pathways. CONCLUSIONS: This is the first study to demonstrate that Galpha(i2)-mediated cardioprotection is suppressed by RGS proteins. These data suggest that RGS proteins may provide novel therapeutic targets to protect the heart from ischaemic injury. |
