Mitochondria-targeted antioxidant SkQR1 selectively protects MDR (Pgp 170)-negative cells against oxidative stress.
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.
Fetisova
Elena K
EK
A N Belozersky Institute of Physico-Chemical Biology and Institute of Mitoengineering, M V Lomonosov Moscow State University, Moscow, Russia.
Avetisyan
Armine V
AV
Izyumov
Denis S
DS
Korotetskaya
Mariya V
MV
Chernyak
Boris V
BV
Skulachev
Vladimir P
VP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D012235:Rhodamines / Q000378:metabolism* / Q000494:pharmacology*
C534903:10-(6'-plastoquinonyl) decylrhodamine 19; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D012235:Rhodamines; D010971:Plastoquinone