Characterization of mice with a deletion of protein kinase G type I in cardiomyocytes and the effect on cardioprotection through either postconditioning or mitochondria-targeted S-nitrosothiol
© Methner et al; licensee BioMed Central Ltd. 2011
Published: 1 August 2011
Protein kinase G type I (PKGI/cGMP kinase I) plays a critical role in survival signalling of pre- and postconditioning. However, it is unclear whether cGKI exerts its protective effects in the cardiomyocyte or if other cardiac cell types are involved, and whether nitric oxide (NO) has cGKI-independent effects on cardiomyocytes mitochondria.
We developed mice with a cardiomyocyte-specific ablation of the cGKI gene (CMG-KO) and tested whether protection against reperfusion injury by ischemic postconditioning (IPost), soluble guanylyl cyclase (sGC) activation, the adenosine A2B receptor (A2BAR), or the mitochondria-targeted S-nitrosothiol (MitoSNO) was affected. MitoSNO accumulates within mitochondria, driven by the membrane potential, where it generates NO• and S-nitrosated thiol proteins .
Methods and results
While cardiomyocyte cGKI is important for the protection afforded via cGMP-signalling, beneficial effects of IPost, activation of the A2BAR, as well as direct NO effects via mitochondrial S-nitrosylation does not depend on cGKI in cardiomyocytes.
- Prime TA, Blaikie FH, Evans C, Nadtochiy SM, James AM, Dahm CC, Vitturi DA, Patel RP, Hiley CR, Abakumova I, Requejo R, Chouchani ET, Hurd TR, Garvey JF, Taylor CT, Brookes PS, Smith RA, Murphy MP: A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2009, 106 (26): 10764-10769.PubMed CentralView ArticlePubMedGoogle Scholar
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