Conjugate for efficient delivery of short interfering RNA (siRNA) into mammalian cells |
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Authors: | Muratovska Aleksandra Eccles Michael R |
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Institution: | MRC-Dunn Human Nutrition Unit, Wellcome Trust/MRC building, Hills Rd, Cambridge CB2 2XY, UK. |
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Abstract: | Cholesterol enrichment of rat liver mitochondria (CHM) impairs atractyloside-induced mitochondrial permeability transition (MPT) due to decreased membrane fluidity. In this study we addressed the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS). Superoxide anion generated by xanthine plus xanthine oxidase triggered mitochondrial swelling and cytochrome c release in CHM, which was prevented by butylated hydroxytoluene, an anti-voltage-dependent anion channel antibody, or cyclosporin A. Furthermore, hydrogen peroxide generated by the combination of ganglioside GD3 and mitochondrial GSH depletion elicited mitochondrial swelling and release of cytochrome c, Smac/Diablo and apoptosis-inducing factor in control mitochondria and CHM. Thus, ROS induce MPT and apoptosome activation regardless of decreased mitochondrial membrane dynamics due to cholesterol enrichment. |
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Keywords: | Author Keywords: Oxidative stress Apoptosis Caspase Glutathione Cholesterol Mitochondrial glutathione Ganglioside GD3 |
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