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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Aug 17

PMID 23951293

Citations 22

Authors

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

Affiliations

Soon will be listed here.

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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