Mitochondria-targeted antioxidant SkQR1 selectively protects MDR (Pgp 170)-negative cells against oxidative stress |
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| Authors: | Elena K. Fetisova |
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| Affiliation: | A.N. Belozersky Institute of Physico-Chemical Biology and Institute of Mitoengineering, M.V. Lomonosov Moscow State University, Moscow 119991, Russia |
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| Abstract: | A conjugate of plastoquinone with decylrhodamine 19 (SkQR1) selectively accumulates in mitochondria of normal and tumor cells. SkQR1 protected the cellular pool of reduced glutathione under oxidative stress. Overexpression of P-glycoprotein (Pgp 170) multidrug resistance pump strongly suppresses accumulation of SkQR1. The inhibitors of Pgp 170 stimulate accumulation of SkQR1 in various cell lines indicating that SkQR1 is a substrate of Pgp 170. The protective effect of SkQR1 against oxidative stress is diminished in the cells overexpressing Pgp 170. It is suggested that mitochondria-targeted antioxidants could selectively protect normal (Pgp 170-negative) cells against the toxic effect of anti-cancer treatments related to oxidative stress. |
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| Keywords: | SkQ1, 10-(6&prime -plastoquinonyl) decyltriphenylphosphonium SkQR1, 10-(6&prime -plastoquinonyl) decylrhodamine 19 MDR, multidrug resistance Pgp 170, P-glycoprotein ROS, reactive oxygen species MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide DTNB, 5,5&prime -dithio-bis(2-nitrobenzoic acid) GSH, glutathione CM-DCFH-DA, 5-(and-6)-chloromethyl-2&prime ,7&prime -dichlorodihydrofluorescein diacetate |
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