Organotellurane-Promoted Mitochondrial Permeability Transition Concomitant with Membrane Lipid Protection against Oxidation

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• 作者：FelipeS. Pessoto ; Priscila A. Faria ; Rodrigo L. O. R. Cunha ; Joã ; o V. Comasseto ; Tiago Rodrigues ; Iseli L. Nantes
• 刊名：Chemical Research in Toxicology
• 出版年：2007
• 出版时间：October 2007
• 年：2007
• 卷：20
• 期：10
• 页码：1453 - 1461
• 全文大小：825K
• 年卷期：v.20,no.10(October 2007)
• ISSN：1520-5010

文摘

Organotelluranes exhibit potent antioxidant properties as well as the ability to react with protein thiol groups and, thereby, they are good models to study the mechanism of the mitochondrial permeability transition (MPT). We evaluated the effects of the concentration of organotelluranes, namely RT-03 and RT-04, on rat liver mitochondria. At the concentration range of 0.25–1.0 µM, organotelluranes did not cause any mitochondrial dysfunction. At the concentration range of 5–10 µM, RT-03 and RT-04 caused the Ca²⁺-dependent opening of the (MPT) pore, regulated by Cyclosporin A. At the concentration range of 15–30 µM the swelling was not inhibited by Cyclosporin A and in the absence of Ca²⁺, a significant decrease of respiratory control ratio was observed due to concomitant phosphorylation impairment and uncoupling, transmembrane potential disruption, depletion of mitochondrial reduced thiol groups, and alterations in the bilayer fluidity. Above 100 µM, the organotelluranes caused complete inhibition of respiratory chain. Over the whole studied concentration range, RT-03 and RT-04 did not induce mitochondrial oxidative stress assessed by using the reactive oxygen and nitrogen species indicator 2′,7′-dichlorodihydrofluorescein diacetate. Further, the organotelluranes also exhibited protective effect against t-butyl hydroperoxide-induced oxidative stress as well as against Fe²⁺/citrate-induced peroxidation of mitochondrial membranes and PCPECL liposomes. These results point out that MPT pore opening can involve damage exclusively to mitochondrial membrane proteins. The exclusive antioxidant activity observed at nanomolar range is also an interesting new finding described in this work.