Diacylglycerol Kinase .ZETA.Rescues G.ALPHA.q-Induced Heart Failure in Transgenic Mice

Niizeki, Takeshi; Takeishi, Yasuchika; Kitahara, Tatsuro; Arimoto, Takanori; Koyama, Yo; Goto, Kaoru; Mende, Ulrike

doi:10.1253/circj.72.309

Cited by 24 publications

(30 citation statements)

References 43 publications

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“…Therefore, atrial remodeling such as atrial fibrosis and dilatation might also be induced through the left ventricular dysfunction and heart failure in this model. In the previous study, 10 it has also been demonstrated that DGKζ inhibits ventricular structural remodeling and rescues Gαq-induced heart failure.…”

Section: Discussionmentioning

confidence: 86%

“…21 Our previous study has demonstrated that Gαq TG mice exhibits the upregulation of fetal gene induction such as atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and beta-MHC, and prominent perivascular and interstitial fibrosis in the left ventricle. 10 In addition, chamber dilatation, cardiac dysfunction, and heart failure as shown by increased left ventricular end-diastoric pressure, reduced +dP/dt, -dP/dt and prolonged Tau were also observed in Gαq TG mice compared with WT and Gαq/DGKζ-TG mice. Four chambers dilatation was also observed in the present study (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…25,26 Our previous study has demonstrated that phosphorylation activities of MAP kinase increased in Gαq TG mice compared with WT and Gαq/DGKζ-TG mice. 10 Nevertheless, overexpression of DGKζ in the hearts of Gαq-TG mice inhibited atrial electrical and structural remodeling. These results suggest that DAG pathway contributes to atrial remodeling in this model.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 The genotypes of the wild-type (WT), Gαq-TG, Gαq/DGKζ-TG mice were identified by polymerase chain reaction (PCR) with the use of tail genomic DNA as previously reported.…”

Section: Animalsmentioning

confidence: 99%

“…[5][6][7][8] We recently generated transgenic mice with cardiac specific overexpression of DGKζ using an α-myosin heavy chain promoter and demonstrated that DGKζ negatively regulated the hypertrophic signaling cascade and resultant ventricular remodeling in response to GPCR agonists. 9 In addition, Niizeki et al 10 have demonstrated that DGKζ inhibits ventricular structural remodeling and rescues Gαq-induced heart failure. However, whether DGKζ inhibits atrial remodeling is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice

Hirose

Takeishi²,

Niizeki

et al. 2009

Heart Rhythm

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

“…10,11 The genotypes of the wild-type (WT), Gαq-TG, Gαq/DGKζ-TG mice were identified by polymerase chain reaction (PCR) with the use of tail genomic DNA as previously reported.…”

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice

Hirose

Takeishi²,

Niizeki

et al. 2009

Heart Rhythm

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Hypertrophy of human embryonic stem cell–derived cardiomyocytes supported by positive feedback between Ca2+ and diacylglycerol signals

Deisl

Fine

Moe

et al. 2019

Pflugers Arch - Eur J Physiol

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Human embryonic stem cell–derived cardiomyocytes develop pronounced hypertrophy in response to angiotensin-2, endothelin-1, and a selected mix of three fatty acids. All three of these responses are accompanied by increases in both basal cytoplasmic Ca 2+ and diacylglycerol, quantified with the Ca 2+ sensor Fluo-4 and a FRET-based diacylglycerol sensor expressed in these cardiomyocytes. The heart glycoside, ouabain (30 nM), and a recently developed inhibitor of diacylglycerol lipases, DO34 (1 μM), cause similar hypertrophy responses, and both responses are accompanied by equivalent increases of basal Ca 2+ and diacylglycerol. These results together suggest that basal Ca 2+ and diacylglycerol form a positive feedback signaling loop that promotes execution of cardiac growth programs in these human myocytes. Given that basal Ca 2+ in myocytes depends strongly on the Na + gradient, we also tested whether nanomolar ouabain concentrations might stimulate Na + /K + pumps, as described by others, and thereby prevent hypertrophy. However, stimulatory effects of nanomolar ouabain (1.5 nM) were not verified on Na + /K + pump currents in stem cell–derived myocytes, nor did nanomolar ouabain block hypertrophy induced by endothelin-1. Thus, low-dose ouabain is not a “protective” intervention under the conditions of these experiments in this human myocyte model. To summarize, the major aim of this study has been to characterize the progression of hypertrophy in human embryonic stem cell–derived cardiac myocytes in dependence on diacylglycerol and Na + gradient changes, developing a case that positive feedback coupling between these mechanisms plays an important role in the initiation of hypertrophy programs.

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Measurements of Diacylglycerols in Skeletal Muscle by Atmospheric Pressure Chemical Ionization Mass Spectrometry

Lee

Kim

Ha³

et al. 2013

Lipids

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Diacylglycerol (DAG) is an intermediate lipid involved in the synthesis of phospholipids and triglycerides. As signaling regulators, DAG activate novel protein kinase C leading to decreased response to insulin in skeletal muscle. Alteration of DAG contents correlates with development of metabolic dysregulation in obese and diabetic conditions. Recent advances in lipidomics using mass spectrometry allow expanded measurements of various lipid species. This study describes a rapid measurement of DAG species using the triple quadrupole mass spectrometry using atmospheric pressure chemical ionization in a positive ion mode. DAG in the cells and muscle tissues were separated depending on differences in chain lengths and degree of unsaturation. The limit of detection and quantification for DAG was 0.2 to 17 pmol for this method. When C2C12 cells were treated with palmitate or oleate, we found a 12-fold and 2-fold DAG increase respectively compared to the no-treatment control. In the muscles of obese db/db mice, DAG levels were elevated by 6-fold compared to those of wild-type skeletal muscles. The present analytical method provides a rapid and sensitive quantification of DAG molecular species from various biological samples and can be used to correlate the degree of metabolic dysregulation with lipotoxic metabolites.

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Diacylglycerol Kinase .ZETA.Rescues G.ALPHA.q-Induced Heart Failure in Transgenic Mice

Cited by 24 publications

References 43 publications

Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice

Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice

Hypertrophy of human embryonic stem cell–derived cardiomyocytes supported by positive feedback between Ca2+ and diacylglycerol signals

Measurements of Diacylglycerols in Skeletal Muscle by Atmospheric Pressure Chemical Ionization Mass Spectrometry

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