1.Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells.
Shah MH1, Liu GS, Thompson EW, Dusting GJ, Peshavariya HM. Breast Cancer Res Treat. 2015 Apr;150(3):523-34. doi: 10.1007/s10549-015-3329-z. Epub 2015 Mar 21.
Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2) have been implicated in development and progression of breast cancer. In the present study, we have evaluated the effects of the superoxide dismutase (SOD) mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 on superoxide and H2O2 formation as well as proliferation, adhesion, and migration of MCF-7 and MDA-MB-231 cells. Superoxide and H2O2 production was examined using dihydroethidium and Amplex red assays, respectively. Cell viability and adhesion were measured using a tetrazolium-based MTT assay. Cell proliferation was determined using trypan blue assay. Cell cycle progression was analyzed using flow cytometry. Clonal expansion of a single cell was performed using a colony formation assay. Cell migration was measured using transwell migration assay. Dual luciferase assay was used to determine NF-κB reporter activity. EUK 134 effectively reduced both superoxide and H2O2, whereas MnTmPyP removed superoxide but enhanced H2O2 formation.
2.The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes.
Kumar A1, Shukla S1, Chauhan AK2, Singh D2, Pandey HP3, Singh C4. Chem Biol Interact. 2015 Apr 25;231:18-26. doi: 10.1016/j.cbi.2015.02.012. Epub 2015 Feb 24.
Oxidative stress is implicated in toxicant-induced inflammation leading to chronic diseases. Polymorphonuclear leukocytes (PMNs) offer the first line of defense against infection in the mammals and protect against inflammation-mediated pathological anomalies. Conversely, activated PMNs contribute to the oxidative stress-mediated damage and inflammation. The study aimed to investigate the status of oxidative stress and antioxidant defense system in the PMNs of rats treated with/without zinc (Zn) and/or paraquat (PQ) in the presence or absence of a synthetic superoxide dismutase/catalase mimetic, a manganese-salen compound-EUK-134 and/or a glutathione precursor, N-acetyl cysteine (NAC). While Zn and/or PQ elevated the total free radical generation, lipid peroxidation (LPO) and catalytic activity of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase alpha 4-4 (GSTA4-4), a pronounced decrease in reduced glutathione (GSH) and glutathione reductase (GR) activity was also observed.
3.Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a.
Chen Z1, Wen L2, Martin M2, Hsu CY2, Fang L2, Lin FM2, Lin TY2, Geary MJ2, Geary GG2, Zhao Y2, Johnson DA2, Chen JW2, Lin SJ2, Chien S2, Huang HD2, Miller YI2, Huang PH2, Shyy JY1. Circulation. 2015 Mar 3;131(9):805-14. doi: 10.1161/CIRCULATIONAHA.114.013675. Epub 2014 Dec 30.
BACKGROUND: Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase-derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element-binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium.
4.Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment.
Yamada T1, Abe M1, Lee J1, Tatebayashi D1, Himori K1, Kanzaki K2, Wada M3, Bruton JD4, Westerblad H4, Lanner JT4. Skelet Muscle. 2015 Jul 9;5:20. doi: 10.1186/s13395-015-0045-7. eCollection 2015.
BACKGROUND: In addition to the primary symptoms arising from inflamed joints, muscle weakness is prominent and frequent in patients with rheumatoid arthritis (RA). Here, we investigated the mechanisms of arthritis-induced muscle dysfunction in rats with adjuvant-induced arthritis (AIA).