Gα(i2)-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart.
Cardiovasc Res
; 91(1): 45-52, 2011 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-21349876
ABSTRACT
AIMS:
Regulator of G protein signalling (RGS) proteins act as molecular 'off switches' that terminate G protein signalling by catalyzing the hydrolysis of Gα-bound GTP to GDP. Many different Gα(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 Gα(i2) rendering it RGS-insensitive (G184S) to determine whether interactions between endogenous RGS proteins and Gα(i2) modulate Gα(i)-mediated protection from ischaemic injury. METHODS ANDRESULTS:
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 Gα(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 Gα(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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión Miocárdica
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Proteínas RGS
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Subunidad alfa de la Proteína de Unión al GTP Gi2
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Infarto del Miocardio
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Miocardio
Idioma:
En
Revista:
Cardiovasc Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos