A. Stepanova et al. / Free Radical Biology and Medicine 120 (2018) S45–S166
Nitric oxide radical (NO) is a signaling molecule involved in several physiological and pathological processes in humans and a new nitratenitrite-NO pathway has emerged as a physiological alternative to the classic pathway of NO formation from L-arginine under hypoxic conditions. In this presentation, the nitrite-dependent NO formation by the rat and human molybdoenzymes xanthine dehydrogenase, oxidase (XD, XO) and aldehyde oxidase (AO) will be discussed. The ability of XD, XO and AO to trigger the NO formation will be shown to be fine-tuned by the dioxygen availability and greatly amplified under the acidic conditions characteristic of ischemia. The potential in vivo physiological relevance of these enzymes for the NO formation (evaluated using HepG2 and HMEC cell lines subjected to hypoxia) will be shown to be significant, with the XD/XO plus AO accounting to as much as 50% of the nitrite-dependent NO formation under hypoxia. Collectively, our results supported that XD/XO and AO can contribute to NO generation under hypoxia inside a living human cell.
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[email protected] References Ref: Maia et al. in J. Biol Inorg. Chem. (2011) 16:443-460, Chem. Rev. (2014) 114:5273-5357, Biochemistry (2015) 54:685-710; J. Biol. Inorg. Chem. (2015) 20:403-433 and in RSC Book (2017) DOI: 10.1039/9781782623915-00001.
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.450
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Glutathione in redox regulation of the development of cancer cell resistance Elena Kalinina, Nikolay Chernov, Maria Novichkova Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
The ratio of reduced glutathione to its oxidized form (GSH/GSSG) is essential for cell viability including its role in redox-dependent regulation of gene expression. The aim of our study was to estimate GSH/GSSG ratio and expression of redox-dependent genes (glutaredoxin, thioredoxin, peroxiredoxin) under development of cancer cell resistance to cisplatin (CDDP) possessed pro-oxidant action. Under development of resistance of human erythroleukemia K562 and ovarian carcinoma SKOV-3 cells to CDDP co-ordinative enhanced expression of genes encoding glutathione synthetase (GS), subunits of γ-glutamylcysteine synthetase (γ-GCSH, γ-GCSL) was found. In addition, the growth of GSH/GSSG, enhanced expression of glutaredoxin (GLRX1, GLRX2), thioredoxin (TRX2), peroxiredoxin (PRDX6) genes as well as elevated level of transcription factor Nrf2 were observed in both types of resistant cells. We suggest that mechanism of development of cancer cell resistance to CDDP can include activation of GSH synthesis de novo, redox-dependent increase in expression of GLRX1, GLRX2, TRX2, PRDX6 genes which are co-ordinative regulated by redoxdependent transcription factor Nrf2 and elevated level of GSH/GSSG.
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[email protected] Acknowledgements The publication was prepared with the support of the “RUDN University Program 5–100”.
http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.451
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Radiation-induced response of mitochondrial energy metabolism in tumor cells Osamu Inanami 1, Kumiko Yamamoto 1, Tomoki Bo 1, Tohru Yamamori 1, Hironobu Yasui 2, Wakako Hiraoka 3 1
Laboratory of Radiation Biology, Department of Applied Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan 2 Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan 3 Department of Physics, School of Science and Technology, Meiji University, Kawasaki, Japan
To evaluate mitochondrial responses in tumor cells exposed to X-rays, a novel ESR oximetry was developed by using lithium 5,9,14,18,23, 27,32,36-octa-n-butoxy-2,3-naphthalocyanine (LiNc-BuO) in the absence and presence of a variety of reagent against mitochondria electron transport chain (ETC), i.e., oligomycin, CCCP and rotenone/antimycin A. This ESR oximetry demonstrated that basal respiration, ATP-linked respiration, proton-leak, maximal respiration and reserve capacity increased in HeLa cells at 24 h after 10 Gy X-irradiation (IR). By standardization of OCR by the mitochondria membrane content, the radiation-induced increase-responses in the respiratory parameters were disappeared, indicating that this increase response was due to increase of mitochondrial content but not activation of mitochondrial respiratory-related enzymes. In addition, ESR spectroscopy of frozen whole HeLa cells showed that mitochondrial semiquinone (SQ) radical was enhanced at 24 h after IR, suggesting increase of electron flow in ETC.
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[email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.452
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Leukotriene B4 mediates vascular oxidative stress and mitochondrial dysfunction in human aortic endothelial cells Mohamad Hafizi Abu Bakar Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor, Penang, Malaysia
The current study focused on the metabolic effects of LTB4 on endothelial and mitochondrial functions in human aortic endothelial cells (HAECs). LTB4 treatment in a dose-dependent manner augmented the degree of mitochondrial superoxide generation in HAECs. Such impairments in mitochondrial integrity and dynamics by increased dynaminrelated protein-1 (Drp1) and fission-1 (Fis1) protein expression but, reduced mitofusin (Mfn)-1 protein expression was noticed in HAECs. Furthermore, LTB4 considerably augmented the expression of Cytochrome C and Bax, but diminished the expression of Bcl-2, thus promoting endothelial apoptosis and inflammation. Additionally, LTB4 treatment resulted in the suppression of phosphatidyl inositol 3- kinase (PI3K)/Akt signaling. Finally, severe vascular oxidative damage and mitochondrial impairments in aorta of transgenic mice expressing human LTB4 (LTB4-Tg) mice were observed compared to wild-type C57BL/6 J mice. Overall, the current investigation discovers a novel mechanism through which LTB4
