title: [Multidrug resistance P-glycoprotein inhibits the antiapoptotic action of mitochondria-targeted antioxidant SkQR1].
abstract: Mitochondria-targeted antioxidants of the SkQR1 family, being accumulated in energized mitochondria, protect cells from oxidative stress by increasing the level of reduced glutathione and decreasing the cell-damaging effect induced by hydrogen peroxide. Using various human transformed cell lines and SkQR1 (a fluorescent member of the SkQ family), we show that SkQRI is ejected from chemotherapy-resistant cells by P-glycoprotein - one of the main transport proteins determining multidrug resistance typical for many neoplastic cells. It is also shown that SkQR1 ejection is neutralized by P-glycoprotein inhibitors (verapamil and pluronic L61). In experiments on K562 cells, it was found that the subline sensitive to chemotherapy is protected by SkQRI from apoptotic action of hydrogen peroxide. Protection of the resistant subline occurs only after inhibition of P-glycoprotein.
authors.forename: E K
authors.initials: EK
authors.lastname: Fetisova
authors.forename: A V
authors.initials: AV
authors.lastname: Avetisian
authors.forename: D S
authors.initials: DS
authors.lastname: Iziumov
authors.forename: M V
authors.initials: MV
authors.lastname: Korotetskaia
authors.forename: V N
authors.initials: VN
authors.lastname: Tashlitskiĭ
authors.forename: V P
authors.initials: VP
authors.lastname: Skulachev
authors.forename: B V
authors.initials: BV
authors.lastname: Cherniak
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005978:Glutathione / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D020014:K562 Cells; D008928:Mitochondria / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D020442:Poloxamer / Q000494:pharmacology*; D012235:Rhodamines / Q000494:pharmacology*; D020298:U937 Cells; D014700:Verapamil / Q000494:pharmacology*
chemical_list: C534903:10-(6'-plastoquinonyl) decylrhodamine 19; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D002121:Calcium Channel Blockers; D012235:Rhodamines; C480965:pluronic L61; D020442:Poloxamer; D006861:Hydrogen Peroxide; D014700:Verapamil; D005978:Glutathione; D010971:Plastoquinone