VDAC: Old protein with new roles in diabetes

Koh Sasaki, Reshma Donthamsetty, Michael Heldak, Young Eun Cho, Brian T. Scott, Ayako Makino

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

A decrease in capillary density due to an increase in endothelial cell apoptosis in the heart is implicated in cardiac ischemia in diabetes. The voltagedependent anion channel (VDAC) plays a crucial role in the regulation of mitochondrial metabolic function and mitochondria-mediated apoptosis. This study is designed to examine the role of VDAC in coronary endothelial dysfunction in diabetes. Endothelial cells (ECs) were more apoptotic in diabetic left ventricle of diabetic mice and mouse coronary ECs (MCECs) isolated from diabetic mice exhibited significantly higher mitochondrial Ca2+ concentration and VDAC protein levels than control MCECs. The expression of VDAC-short hairpin RNA (shRNA) not only decreased the resting mitochondrial Ca2+ concentration but also attenuated mitochondrial Ca2+ uptake in diabetic MCECs. Furthermore, the downregulation of VDAC in diabetic MCECs significantly decreased mitochondrial superoxide anion (O2-) production and the activity of the mitochondrial permeability transition pore (mPTP) opening (an indirect indicator of cell apoptosis) toward control levels. These data suggest that the increased VDAC level in diabetic MCECs is responsible for increased mitochondrial Ca2+ concentration, mitochondrial O2- production, and mPTP opening activity. Normalizing VDAC protein level may help to decrease endothelial cell apoptosis, increase capillary density in the heart, and subsequently decrease the incidence of cardiac ischemia in diabetes.

Original languageEnglish (US)
Pages (from-to)C1055-C1060
JournalAmerican Journal of Physiology - Cell Physiology
Volume303
Issue number10
DOIs
StatePublished - Nov 15 2012

Keywords

  • Apoptosis
  • Ca overload in mitochondria
  • Vascular complications
  • Vascular rarefaction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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