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http://purl.uniprot.org/citations/18219172http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18219172http://www.w3.org/2000/01/rdf-schema#comment"

Background

The G alpha q protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in the development of cardiac hypertrophy and heart failure (HF). It has been reported that the expression of a constitutively active mutant of the G protein alpha q subunit in the hearts of transgenic mice (G alpha q-TG) induces cardiac hypertrophy and lethal HF. DAG kinase (DGK) catalyzes DAG and controls its cellular levels, thus acting as a regulator of GPCR signaling. It has been found that transgenic mice with cardiac-specific overexpression of DGK zeta (DGK zeta-TG) inhibit GPCR agonist-induced activation of the DAG-PKC signaling and subsequent cardiac hypertrophy, so this study tested the hypothesis that DGK zeta could rescue G alpha q-TG mice from developing HF.

Methods and results

Double transgenic mice (G alpha q/DGK zeta-TG) with cardiac-specific overexpression of both DGK zeta and G alpha q were generated by crossing G alpha q-TG with DGK zeta-TG mice, and the pathophysiological consequences were analyzed. DGK zeta prevented cardiac dysfunction, determined by dilatation of left ventricular (LV) dimensions, reduction of LV fractional shortening, and marked increases in LV end-diastolic pressure in G alpha q-TG mice. Translocation of PKC isoforms, phosphorylation activity of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in G alpha q-TG mice were attenuated by DGK zeta. DGK zeta improved the survival rate of G alpha q-TG mice.

Conclusions

These results demonstrate the first evidence that DGK zeta blocks cardiac dysfunction and progression to lethal HF by activated G alpha q protein without detectable adverse effects in the in-vivo heart and suggest that DGK zeta is a novel therapeutic target for HF."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.org/dc/terms/identifier"doi:10.1253/circj.72.309"xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Koyama Y."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Goto K."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Kubota I."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Kitahara T."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Arimoto T."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Takeishi Y."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Mende U."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/author"Niizeki T."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/name"Circ J"xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/pages"309-317"xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/title"Diacylglycerol kinase zeta rescues G alpha q-induced heart failure in transgenic mice."xsd:string
http://purl.uniprot.org/citations/18219172http://purl.uniprot.org/core/volume"72"xsd:string
http://purl.uniprot.org/citations/18219172http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18219172
http://purl.uniprot.org/citations/18219172http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18219172
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http://purl.uniprot.org/uniprot/#_A2AHK0-mappedCitation-18219172http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18219172
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