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Vanadyl ions binding to GroEL (HSP60) and inducing its depolymerization

机译:钒离子与GroEL(HSP60)结合并诱导其解聚

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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 investigated the potential targets of vanadium in mitochondria. Vanadyl ions were found to bind to mitochondria from rat liver with a stoichiometry of 244±58 nmol/mg protein and an apparent dissociation constant (K_d) of (2.0±0.8)x10~(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 depolymerization of homo-oligomeric HSP60 (GroEL). HSP60 is an indispensable molecular chaperone and involved 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.
机译:已知几种钒化合物具有降血糖和抗癌作用。但是,其药理和毒理作用的机制尚不清楚。在这项工作中,我们调查了线粒体中钒的潜在目标。钒离子与大鼠肝脏线粒体结合,化学计量比为244±58 nmol / mg,表观解离常数(K_d)为(2.0±0.8)x10〜(16)mol / L。使用尺寸排阻色谱法,分离出钒结合蛋白,并通过质谱分析和免疫分析鉴定为60 kDa热激蛋白(HSP60)。另外,发现钒氧离子的结合导致均聚物HSP60(GroEL)解聚。 HSP60是必不可少的分子伴侣,参与多种炎症和自身免疫性疾病的发病机制,例如1型糖尿病。我们的结果表明,HSP60可能是涉及钒化合物的生物学和/或毒理学作用的新型重要靶标。

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