Persistent Overexpression of Phosphoglycerate Mutase, a Glycolytic Enzyme, Modifies Energy Metabolism and Reduces Stress Resistance of Heart in Mice

Junji Okuda, Shinnichiro Niizuma, Tetsuo Shioi, Takao Kato, Yasutaka Inuzuka, Tsuneaki Kawashima, Yodo Tamaki, Akira Kawamoto, Yohei Tanada, Yoshitaka Iwanaga, Michiko Narazaki, Tetsuya Matsuda, Souichi Adachi, Tomoyoshi Soga, Genzou Takemura, Hiroshi Kondoh, Toru Kita, Takeshi Kimura

Research output: Contribution to journalArticle

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Abstract

Background:Heart failure is associated with changes in cardiac energy metabolism. Glucose metabolism in particular is thought to be important in the pathogenesis of heart failure. We examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function.Methods and Results:Transgenic mice constitutively overexpressing Pgam2 in a heart-specific manner were generated, and cardiac energy metabolism and function were analyzed. Cardiac function at rest was normal. The uptake of analogs of glucose or fatty acids and the phosphocreatine/βATP ratio at rest were normal. A comprehensive metabolomic analysis revealed an increase in the levels of a few metabolites immediately upstream and downstream of Pgam2 in the glycolytic pathway, whereas the levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered. The capacity for respiration by isolated mitochondria in vitro was decreased, and that for the generation of reactive oxygen species (ROS) in vitro was increased. Impaired cardiac function was observed in response to dobutamine. Mice developed systolic dysfunction upon pressure overload.Conclusions:Constitutive overexpression of Pgam2 modified energy metabolism and reduced stress resistance of heart in mice.

Original languageEnglish
Article numbere72173
JournalPLoS One
Volume8
Issue number8
DOIs
Publication statusPublished - 2013 Aug 12

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Phosphoglycerate Mutase
phosphoglyceric acids
stress tolerance
energy metabolism
Energy Metabolism
Metabolites
heart
mice
glycolysis
heart failure
Enzymes
cardiac output
metabolites
enzymes
Heart Failure
phosphocreatine
Glucose
glucose
Mitochondria
Dobutamine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Persistent Overexpression of Phosphoglycerate Mutase, a Glycolytic Enzyme, Modifies Energy Metabolism and Reduces Stress Resistance of Heart in Mice. / Okuda, Junji; Niizuma, Shinnichiro; Shioi, Tetsuo; Kato, Takao; Inuzuka, Yasutaka; Kawashima, Tsuneaki; Tamaki, Yodo; Kawamoto, Akira; Tanada, Yohei; Iwanaga, Yoshitaka; Narazaki, Michiko; Matsuda, Tetsuya; Adachi, Souichi; Soga, Tomoyoshi; Takemura, Genzou; Kondoh, Hiroshi; Kita, Toru; Kimura, Takeshi.

In: PLoS One, Vol. 8, No. 8, e72173, 12.08.2013.

Research output: Contribution to journalArticle

Okuda, J, Niizuma, S, Shioi, T, Kato, T, Inuzuka, Y, Kawashima, T, Tamaki, Y, Kawamoto, A, Tanada, Y, Iwanaga, Y, Narazaki, M, Matsuda, T, Adachi, S, Soga, T, Takemura, G, Kondoh, H, Kita, T & Kimura, T 2013, 'Persistent Overexpression of Phosphoglycerate Mutase, a Glycolytic Enzyme, Modifies Energy Metabolism and Reduces Stress Resistance of Heart in Mice', PLoS One, vol. 8, no. 8, e72173. https://doi.org/10.1371/journal.pone.0072173
Okuda, Junji ; Niizuma, Shinnichiro ; Shioi, Tetsuo ; Kato, Takao ; Inuzuka, Yasutaka ; Kawashima, Tsuneaki ; Tamaki, Yodo ; Kawamoto, Akira ; Tanada, Yohei ; Iwanaga, Yoshitaka ; Narazaki, Michiko ; Matsuda, Tetsuya ; Adachi, Souichi ; Soga, Tomoyoshi ; Takemura, Genzou ; Kondoh, Hiroshi ; Kita, Toru ; Kimura, Takeshi. / Persistent Overexpression of Phosphoglycerate Mutase, a Glycolytic Enzyme, Modifies Energy Metabolism and Reduces Stress Resistance of Heart in Mice. In: PLoS One. 2013 ; Vol. 8, No. 8.
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abstract = "Background:Heart failure is associated with changes in cardiac energy metabolism. Glucose metabolism in particular is thought to be important in the pathogenesis of heart failure. We examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function.Methods and Results:Transgenic mice constitutively overexpressing Pgam2 in a heart-specific manner were generated, and cardiac energy metabolism and function were analyzed. Cardiac function at rest was normal. The uptake of analogs of glucose or fatty acids and the phosphocreatine/βATP ratio at rest were normal. A comprehensive metabolomic analysis revealed an increase in the levels of a few metabolites immediately upstream and downstream of Pgam2 in the glycolytic pathway, whereas the levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered. The capacity for respiration by isolated mitochondria in vitro was decreased, and that for the generation of reactive oxygen species (ROS) in vitro was increased. Impaired cardiac function was observed in response to dobutamine. Mice developed systolic dysfunction upon pressure overload.Conclusions:Constitutive overexpression of Pgam2 modified energy metabolism and reduced stress resistance of heart in mice.",
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AU - Shioi, Tetsuo

AU - Kato, Takao

AU - Inuzuka, Yasutaka

AU - Kawashima, Tsuneaki

AU - Tamaki, Yodo

AU - Kawamoto, Akira

AU - Tanada, Yohei

AU - Iwanaga, Yoshitaka

AU - Narazaki, Michiko

AU - Matsuda, Tetsuya

AU - Adachi, Souichi

AU - Soga, Tomoyoshi

AU - Takemura, Genzou

AU - Kondoh, Hiroshi

AU - Kita, Toru

AU - Kimura, Takeshi

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