title: Radioprotective effects of mitochondria-targeted antioxidant SkQR1.
abstract: We show here that mitochondria-targeted antioxidant composed of plastoquinone conjugated through hydrocarbon linker with cationic rhodamine 19 (SkQR1) protected against nuclear DNA damage induced by gamma radiation in K562 erythroleukemia cells. We also demonstrate that SkQR1 prevented the early (1 h postirradiation) accumulation of phosphorylated histone H2AX (γ-H2AX) an indicator of DNA double-strand break formation, as well as the radiation-induced increase in chromosomal aberrations. These data suggested that nuclear DNA damage induced by gamma radiation may be mediated by mitochondrial reactive oxygen species (ROS) production. We show that SkQR1 suppressed delayed accumulation of ROS 32 h after irradiation probably by inhibiting mitochondrial ROS-induced ROS release mechanisms. This suggests that mitochondria-targeted antioxidants may protect cells from the late consequences of radiation exposure related to delayed oxidative stress. We have previously reported that SkQRl is the substrate of multidrug resistance pump P-glycoproten (Pgp 170) and selectively protects Pgp 170-negative cells against oxidative stress. In line with this finding, we demonstrate here that SkQR1 did not protect Pgp170-positive K562 subline against DNA damage induced by gamma radiation. The selective radioprotection of normal Pgp 170-negative cells by mitochondria-targeted antioxidants could be a promising strategy to increase the efficiency of radiotherapy for multidrug-resistant tumors.
authors.affiliation: a  Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Vorobyevy Gory 1, Moscow 119991, Russia.
authors.forename: Elena K
authors.initials: EK
authors.lastname: Fetisova
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Antoschina
authors.forename: Varvara D
authors.initials: VD
authors.lastname: Cherepanynets
authors.forename: Denis S
authors.initials: DS
authors.lastname: Izumov
authors.forename: Igor I
authors.initials: II
authors.lastname: Kireev
authors.forename: Roman I
authors.initials: RI
authors.lastname: Kireev
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Lyamzaev
authors.forename: Nikolay I
authors.initials: NI
authors.lastname: Riabchenko
authors.forename: Boris V
authors.initials: BV
authors.lastname: Chernyak
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D020014:K562 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012235:Rhodamines / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C534903:10-(6'-plastoquinonyl) decylrhodamine 19; D000975:Antioxidants; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D012235:Rhodamines; D010971:Plastoquinone