Heart failure & cardiomyopathies
Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure
Authors' conclusion
Our findings identify NDPK-C as an essential requirement for both the interaction between NDPK isoforms and between NDPK isoforms and G proteins. NDPK-C is a novel critical regulator of β-adrenoceptor/cAMP signaling and cardiac contractility.
Study context
- Population
- Human end-stage heart failure (HF) myocardium, rats with long-term isoprenaline stimulation, rat neonatal cardiomyocytes, zebrafish embryos and NDPK-B knockout mice
- Outcome
- Role of NDPK-C in cardiac cAMP formation and contractility
Main finding
As reported in the abstract
- NDPK-C essential for formation of an NDPK-B/G protein complex
- NDPK-C protein and mRNA upregulated in end-stage human HF, in rats after long-term isoprenaline and in isoprenaline-incubated rat neonatal cardiomyocytes
- Isoprenaline promoted translocation of NDPK-C to the plasma membrane
- NDPK-C overexpression increased cAMP and sensitized cardiomyocytes to isoprenaline-induced augmentation of contractility; knockdown decreased cAMP
- NDPK-C depletion in zebrafish embryos caused cardiac edema and ventricular dysfunction
- NDPK-B knockout mice: unaltered NDPK-C expression, but contractile dysfunction and exacerbated cardiac remodeling under long-term isoprenaline
- In human end-stage HF, NDPK-C/Gαi2 complex formation increased and NDPK-C/Gαs interaction decreased
Original publication
Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure. Circulation. Published 7 December 2016. doi:10.
Summarised from the published abstract; every number is checked against it