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Association of Hexokinase and Voltage Dependent Anion Channel in Cardiac Hypertrophy
Author(s) -
Saran Varun,
Saeedi Ramesh,
Wambolt Richard,
Allard Micheal F.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.362.1
Subject(s) - voltage dependent anion channel , glycolysis , hexokinase , medicine , endocrinology , muscle hypertrophy , skeletal muscle , vasopressin , myocyte , biology , chemistry , biochemistry , metabolism , bacterial outer membrane , gene , escherichia coli
Glycolysis is accelerated in pathologic cardiac hypertrophy but the cellular mechanism(s) responsible are not yet fully understood. Binding of hexokinase (HK), a key enzyme in control of glycolysis in heart and other tissues, to mitochondrial voltage dependent anion channels (VDAC) is viewed as a major factor responsible for insulin‐induced glucose uptake in skeletal muscle and acceleration of glycolysis in malignant neoplasms. We hypothesized that binding of HK to VDAC is increased in pathologically hypertrophied heart muscle cells and hearts. Binding of HK to VDAC was assessed by co‐immunoprecipitation and immunoblot analysis of lysates from cultured H9c2 cells hypertrophied by exposure to arginine vasopressin (AVP) and from hypertrophied hearts in mice with an abdominal aortic constriction (AAC). Cells unexposed to AVP and sham‐operated mice served as Controls. AVP‐treated H9c2 cells and hearts from mice with an AAC were hypertrophied 20 to 30% with rates of glycolysis 30 to 50% greater than Controls. Co‐immunprecipitation experiments indicated that association of HK with VDAC was significantly increased in hypertrophied H9c2 cells and in hypertrophied mouse heart tissue. This supports the concept that binding of HK to VDAC is increased in the setting of pathologic cardiac hypertrophy and may play a role in the acceleration of glycolysis observed. Supported by the Canadian Institutes of Health Research