title: [Multidrug resistance p-glycoprotein inhibits the antiapoptotic action of mitochondria-targeted antioxidant SkQR1].
abstract: Mitochondria-targeted antioxidants of the SkQRI 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 SkQR1 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 SkQR1 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*; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; 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; D014700:Verapamil; D010971:Plastoquinone