title: Influence of SkQ1 on Expression of Nrf2 Gene, ARE-Controlled Genes of Antioxidant Enzymes and Their Activity in Rat Blood Leukocytes under Oxidative Stress.
abstract: The study demonstrated that oxidative stress induced by hyperoxia (0.5 MPa for 90 min) resulted in reduction of mRNA levels of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes (SOD1, CAT, GPx4) in peripheral blood leukocytes of rats. The changes in gene expression profiles under hyperoxia were accompanied by disbalance of activity of antioxidant enzymes in the leukocytes, namely activation of superoxide dismutase and inhibition of catalase, glutathione peroxidase, and glutathione-S-transferase. Pretreatment of rats with SkQ1 (50 nmol/kg for five days) significantly increased mRNA levels of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes SOD2 and GPx4 and normalized the transcriptional activity of the SOD1 and CAT genes in the leukocytes in hyperoxia-induced oxidative stress. At the same time, the activity of catalase and glutathione peroxidase was increased, and the activity of superoxide dismutase and glutathione-S-transferase returned to the control level. It is hypothesized that protective effect of SkQ1 in hyperoxia-induced oxidative stress can be realized via a direct antioxidant property and the stimulation of the Keap1/Nrf2 redox-sensitive signaling system.
authors.affiliation: Southern Federal University, Academy of Biology and Biotechnology, Department of Biochemistry and Microbiology, Rostov-on-Don, 344090, Russia. natmilut@rambler.ru.
authors.forename: V V
authors.initials: VV
authors.lastname: Vnukov
authors.forename: O I
authors.initials: OI
authors.lastname: Gutsenko
authors.forename: N P
authors.initials: NP
authors.lastname: Milutina
authors.forename: I V
authors.initials: IV
authors.lastname: Kornienko
authors.forename: A A
authors.initials: AA
authors.lastname: Ananyan
authors.forename: A O
authors.initials: AO
authors.lastname: Danilenko
authors.forename: S B
authors.initials: SB
authors.lastname: Panina
authors.forename: A A
authors.initials: AA
authors.lastname: Plotnikov
authors.forename: M S
authors.initials: MS
authors.lastname: Makarenko
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D023421:Models, Animal; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics
chemical_list: C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D002374:Catalase; D005979:Glutathione Peroxidase; C523860:glutathione peroxidase 4, rat; D013482:Superoxide Dismutase; D010971:Plastoquinone