Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure
BACKGROUND: -Chronic heart failure (HF) is associated with altered signal transduction via beta-adrenoceptors and G proteins, and with reduced cAMP formation. Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of end-stage HF patients, but the functional consequences of this...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2017
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| Sorozat: | CIRCULATION
135 No. 9 |
| doi: | 10.1161/CIRCULATIONAHA.116.022852 |
| mtmt: | 3150733 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/15879 |
| LEADER | 03167nab a2200277 i 4500 | ||
|---|---|---|---|
| 001 | publ15879 | ||
| 005 | 20190628105459.0 | ||
| 008 | 190628s2017 hu o 0|| zxx d | ||
| 022 | |a 0009-7322 | ||
| 024 | 7 | |a 10.1161/CIRCULATIONAHA.116.022852 |2 doi | |
| 024 | 7 | |a 3150733 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 2 | |a Abu-Taha Issam H. | |
| 245 | 1 | 0 | |a Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure |h [elektronikus dokumentum] / |c Abu-Taha Issam H. |
| 260 | |c 2017 | ||
| 300 | |a 881-897 | ||
| 490 | 0 | |a CIRCULATION |v 135 No. 9 | |
| 520 | 3 | |a BACKGROUND: -Chronic heart failure (HF) is associated with altered signal transduction via beta-adrenoceptors and G proteins, and with reduced cAMP formation. Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of end-stage HF patients, but the functional consequences of this are largely unknown, particularly for NDPK-C. Here, we investigated the potential role of NDPK-C in cardiac cAMP formation and contractility. METHODS: -Real-time PCR, (Far) Western blot, immunoprecipitation, and immunocytochemistry were used to study the expression, interaction with G proteins, and localization of NDPKs. cAMP levels were determined using immunoassays or fluorescent resonance energy transfer, and contractility was determined in cardiomyocytes (cell shortening) and in vivo (fractional shortening). RESULTS: -NDPK-C was essential for the formation of a NDPK-B/G proteins complex. Protein and mRNA levels of NDPK-C were up-regulated in end-stage human HF, in rats following chronic isoprenaline (ISO) stimulation through osmotic minipumps, and after incubation of rat neonatal cardiomyocytes with ISO. ISO also promoted translocation of NDPK-C to the plasma membrane. Overexpression of NDPK-C in cardiomyocytes increased cAMP levels and sensitized cardiomyocytes to ISO-induced augmentation of contractility, whereas NDPK-C knockdown decreased cAMP levels. In vivo, depletion of NDPK-C in zebrafish embryos caused cardiac edema and ventricular dysfunction. NDPK-B knockout mice had unaltered NDPK-C expression, but showed contractile dysfunction and exacerbated cardiac remodeling during chronic ISO stimulation. In human end-stage HF, the complex formation between NDPK-C and Galphai2 was increased, whereas NDPK-C/Galphas interaction was decreased, producing a switch that may contribute to an NDPK-C-dependent cAMP-reduction in HF. CONCLUSIONS: -Our findings identify NDPK-C as an essential requirement for both the interaction between NDPK isoforms and with G proteins. NDPK-C is a novel critical regulator of beta-adrenoceptor/cAMP signaling and cardiac contractility. By switching from Galphas to Galphai2 activation, NDPK-C may contribute to lower cAMP levels and the related contractile dysfunction in HF. | |
| 700 | 0 | 1 | |a Heijman Jordi |e aut |
| 700 | 0 | 1 | |a Hippe Hans-Jörg |e aut |
| 700 | 0 | 1 | |a Wolf Nadine M. |e aut |
| 700 | 0 | 2 | |a El-Armouche Ali |e aut |
| 700 | 0 | 2 | |a Baczkó István |e aut |
| 700 | 0 | 2 | |a Varró András |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/15879/1/AbuTahaBaczkoVarroCirculation2017final.pdf |z Dokumentum-elérés |