Vanadium compounds induced mitochondria permeability transition pore (PTP) opening related to oxidative stress.

Abstract

Vanadium compounds have been regarded as promising in therapeutic treatment of diabetes and in cancer prevention. In the present work, we studied the effects of vanadium compounds on mitochondria to investigate the mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with a variety of vanadium compounds, i.e. VOSO(4), NaVO(3), and vanadyl complexes with organic ligands. Our studies indicated that VO(2+), VO(3)(-), VO(acac)(2) and VOcit (1-100microM) could induce mitochondrial swelling in a concentration dependent manner and disrupt mitochondrial membrane potential (Deltapsi(m)) in a time dependent manner, which is quite different from the rapid Deltapsi(m) collapse caused by Ca(2+) or CCCP (carbonyl cyanide m-chlorophenylhydrazone, a mitochondrial uncoupling reagent). Release of cytochrome c (Cyt c) was observed and could be inhibited by cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore (PTP). Interestingly, VOdipic caused release of Cyt c without mitochondrial swelling and Deltapsi(m) disruption, an action previously only observed on the Bax protein, suggesting a potentially role of VOdipic in regulating PTP opening. In addition, all the vanadium compounds tested stimulated mitochondrial production of reactive oxygen species (ROS). Antioxidants, i.e. vitamin C and E, significantly delayed the Deltapsi(m) disruption. Overall, our experimental evidence indicated vanadium compounds exhibited multiple actions on mitochondria. Vanadium compounds did induce oxidative stress on mitochondrial and thus caused PTP opening, which led to collapse of Deltapsi(m) and Cyt c release as the initiation of cell apoptosis.

• Authors: Yuebin Zhao, Lihua Ye, Huixue Liu, Qing Xia, Yue Zhang, Xiaoda Yang, Kui Wang
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 104 Issue 4 Pg. 371-8 (Apr 2010) ISSN: 1873-3344 [Electronic] United States
• PMID: 20015552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Enzyme Inhibitors
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Reactive Oxygen Species
• Vanadium Compounds
• Cyclosporine
• Electron Transport Complex II

Topics

• Animals
• Antioxidants (pharmacology)
• Cyclosporine (pharmacology)
• Electron Transport Complex II (metabolism)
• Enzyme Inhibitors (pharmacology)
• Male
• Membrane Potential, Mitochondrial (drug effects, physiology)
• Mitochondria, Liver (drug effects, metabolism, pathology)
• Mitochondrial Membrane Transport Proteins (drug effects, metabolism)
• Mitochondrial Permeability Transition Pore
• Molecular Structure
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Vanadium Compounds (chemistry, pharmacology)