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Several vanadium compounds have been known for the hypoglycemic and anticancer effects. However, the mechanisms of the pharmacological and toxicological effects were not clear. In this work, we in- vestigated the potential targets of vanadium in mitochondria. Vanadyl ions were found to bind to mi- tochondria from rat liver with a stoichiometry of 244±58 nmol/mg protein and an apparent dissocia- tion constant (Kd) of (2.0±0.8)×10·16 mol/L. Using size exclusion chromatography, a vanadium-binding protein was isolated and identified to be the 60-kDa heat shock protein (HSP60) by mass spectrometry analysis and immunoassays. Additionally, binding of vanadyl ions was found to result in depolymeri- zation of homo-oligomeric HSP60 (GroEL). HSP60 is an indispensable molecular chaperone and in- volved in many kinds of pathogenesis of inflammatory and autoimmune diseases, e.g. type 1 diabetes. Our results suggested that HSP60 could be a novel important target involved in the biological and/or toxicological effects of vanadium compounds.
Several, vanadium compounds have been known for the hypoglycemic and anticancer effects. However, the mechanisms of the pharmacological and toxicological effects were not clear. In this work, we in- vestigated the potential targets of vanadium in mitochondria. Vanadyl ions were found to bind to mi- tochondria from rat liver with a stoichiometry of 244 ± 58 nmol / mg protein and an apparent dissociation constant (Kd) of (2.0 ± 0.8) × 10 · 16 mol / L Using size exclusion chromatography, a vanadium-binding protein was isolated and identified to be the 60-kDa heat shock protein (HSP60) by mass spectrometry analysis and immunoassays. Additionally, binding of vanadyl ions was found to result in depolymeri- zation of homo-oligomeric HSP60 (GroEL). HSP60 is an indispensable molecular chaperone and in- volved in many kinds of pathogenesis of inflammatory and autoimmune diseases, eg type 1 diabetes. Our results suggested that HSP60 could be novel important target involved in the biological and / or toxicological effects of vanadium compounds.