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https://www.readbyqxmd.com/read/28429737/the-glutamate-cystine-xct-antiporter-antagonizes-glutamine-metabolism-and-reduces-nutrient-flexibility
#1
Chun-Shik Shin, Prashant Mishra, Jeramie D Watrous, Valerio Carelli, Marilena D'Aurelio, Mohit Jain, David C Chan
As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc(-)), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28420170/fisetin-protects-pc12-cells-from-tunicamycin-mediated-cell-death-via-reactive-oxygen-species-scavenging-and-modulation-of-nrf2-driven-gene-expression-sirt1-and-mapk-signaling-in-pc12-cells
#2
Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen, Ming-Jiuan Wu
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28390315/glutathione-inhibits-antibody-and-complement-mediated-immunologic-cell-injury-via-multiple-mechanisms
#3
Zhen Zhang, Xiling Zhang, Xin Fang, Manabu Niimi, Yanru Huang, Honglan Piao, Shan Gao, Jianglin Fan, Jian Yao
Antioxidant glutathione (GSH) plays an important role in the regulation of immunity. However, little is known about its effects on humoral immunity, especially its action on effector molecules like antibody and complement. Given that these molecules contain abundant disulfide bonds, we speculated that GSH might influence the action of these proteins via its thiol function. Using a model of a glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we addressed this hypothesis. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused a complement-dependent cell lysis, which was completely blocked by GSH...
March 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28384716/analysis-of-mthfr-cbs-glutathione-taurine-and-hydrogen-sulfide-levels-in-retinas-of-hyperhomocysteinemic-mice
#4
Xuezhi Cui, Soumya Navneet, Jing Wang, Penny Roon, Wei Chen, Ming Xian, Sylvia B Smith
Purpose: Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28381035/quasi-supercontinuum-source-in-the-extreme-ultraviolet-using-multiple-frequency-combs-from-high-harmonic-generation
#5
Martin Wünsche, Silvio Fuchs, Stefan Aull, Jan Nathanael, Max Möller, Christian Rödel, Gerhard G Paulus
A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics...
March 20, 2017: Optics Express
https://www.readbyqxmd.com/read/28347687/effects-of-chronic-inhalation-of-electronic-cigarettes-containing-nicotine-on-glial-glutamate-transporters-and-%C3%AE-7-nicotinic-acetylcholine-receptor-in-female-cd-1-mice
#6
Fawaz Alasmari, Laura E Crotty Alexander, Jessica A Nelson, Isaac T Schiefer, Ellen Breen, Christopher A Drummond, Youssef Sari
Alteration in glutamate neurotransmission has been found to mediate the development of drug dependence, including nicotine. We and others, through using western blotting, have reported that exposure to drugs of abuse reduced the expression of glutamate transporter-1 (GLT-1) as well as cystine/glutamate antiporter (xCT), which consequently increased extracellular glutamate concentrations in the mesocorticolimbic area. However, our previous studies did not reveal any changes in glutamate/aspartate transporter (GLAST) following exposure to drugs of abuse...
March 27, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28345346/thermally-activated-delayed-fluorescence-and-aggregation-induced-emission-with-through-space-charge-transfer
#7
Hiroyuki Tsujimoto, Dong-Gwang Ha, Georgios Markopoulos, Hyun Sik Chae, Marc A Baldo, Timothy M Swager
Emissive molecules comprising a donor and an acceptor bridged by 9,9-dimethylxanthene, were studied (XPT, XCT, and XtBuCT). The structures position the donor and acceptor with cofacial alignment at distances of 3.3-3.5 Å wherein efficient spatial charge transfer can occur. The quantum yields were enhanced by excluding molecular oxygen and thermally activated delayed fluorescence with lifetimes on the order of microseconds was observed. Although the molecules displayed low quantum yields in solution, higher quantum yields were observed in the solid state...
March 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28289330/the-heterogeneity-of-cancer-stem-like-cells-at-the-invasive-front
#8
Go J Yoshida
Cancer stem-like cells exhibit the multi-functional roles to survive and persist for a long period in the minimal residual disease after the conventional anti-cancer treatments. Cancer stem-like cells of solid malignant tumors which highly express CD44v8-10, the variant isoform of CD44 generated by alternative splicing, has a resistance to redox stress by the robust production of glutathione mediated by ESRP1-CD44v-xCT (cystine/glutamate antiporter) axis. It has been reported that CD44v and c-Myc tend to show the inversed expression pattern at the invasive front of the aggressive tumors...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28273808/role-of-ul3-in-multidrug-resistance-in-p53-mutated-lung-cancer-cells
#9
Annapina Russo, Assunta Saide, Silvia Smaldone, Raffaella Faraonio, Giulia Russo
Cancer is one of the most common causes of death among adults. Chemotherapy is crucial in determining patient survival and quality of life. However, the development of multidrug resistance (MDR) continues to pose a significant challenge in the management of cancer. In this study, we analyzed the role of human ribosomal protein uL3 (formerly rpL3) in multidrug resistance. Our studies revealed that uL3 is a key determinant of multidrug resistance in p53-mutated lung cancer cells by controlling the cell redox status...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28258140/ecological-and-evolutionary-insights-into-xanthomonas-citri-pathovar-diversity
#10
Kanika Bansal, Samriti Midha, Sanjeet Kumar, Prabhu B Patil
Citrus canker, caused by Xanthomonas citri pv. citri, is a serious disease of citrus plants worldwide. Earlier phylogenetic studies using housekeeping genes revealed that X. citri pv. citri is related to many other pathovars, which can be collectively referred as Xanthomonas citri pathovars (XCPs). From the present study, we report the genome sequences of 18 XCPs and compared them with four XCPs available in the public domain. In a tree based on phylogenomic marker genes, all the XCPs form a monophyletic cluster, suggesting their origin from a common ancestor...
May 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28253902/sulfasalazine-attenuates-evading-anticancer-response-of-cd133-positive-hepatocellular-carcinoma-cells
#11
Yeonhwa Song, Jaewoo Jang, Tae-Hoon Shin, Sang Mun Bae, Jin-Sun Kim, Kang Mo Kim, Seung-Jae Myung, Eun Kyung Choi, Haeng Ran Seo
BACKGROUND: CD133-positive cells in hepatocellular carcinoma (HCC) exhibit cancer stem cell (CSC)-like properties as well as resistance to chemotherapeutic agents and ionizing radiation; however, their function remains unknown. In this paper, we identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy. METHODS: We applied an alternative approach to enrich the CD133-positive HCC population by manipulating 3D culture conditions...
March 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28202313/the-complex-roles-of-stat3-and-stat5-in-maintaining-redox-balance-lessons-from-stat-mediated-xct-expression-in-cancer-cells
#12
Katja Linher-Melville, Gurmit Singh
STAT3 and STAT5 mediate diverse cellular processes, transcriptionally regulating gene expression and interacting with cytoplasmic proteins. Their canonical activity is stimulated by cytokines/growth factors through JAK-STAT signaling. As targets of oncogenes with intrinsic tyrosine kinase activity, STAT3 and STAT5 become constitutively active in hematologic neoplasms and solid tumors, promoting cell proliferation and survival and modulating redox homeostasis. This review summarizes reactive oxygen species (ROS)-regulated STAT activation and how STATs influence ROS production...
February 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28185919/rheostatic-cd44-isoform-expression-and-its-association-with-oxidative-stress-in-human-malignant-mesothelioma
#13
Shan Hwu Chew, Yasumasa Okazaki, Shinya Akatsuka, Shenqi Wang, Li Jiang, Yuuki Ohara, Fumiya Ito, Hideyuki Saya, Yoshitaka Sekido, Shinya Toyokuni
CD44 exists as a standard (CD44s) isoform and different variant isoforms (CD44v) due to alternative splicing. While the complex nature of these different isoforms has not been fully elucidated, CD44v expression has been shown to exert oncogenic effects by promoting tumor progression, metastasis and resistance of tumor cells to chemotherapy. One of the CD44v isoforms, CD44v8-10, was recently shown to protect cancer cells from oxidative stress by increasing the synthesis of glutathione (GSH). However, data regarding CD44 isoform expression in malignant mesothelioma (MM) are still lacking...
February 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28167131/erythropoietin-induced-cytoprotection-in-intestinal-epithelial-cells-is-linked-to-system-xc
#14
Colin Martin, Mikita Patel, Miguel Melendez-Ferro, Brian Sims
Necrotizing enterocolitis is a common but serious complication among premature babies. Currently, there are limited treatment options. These include intensive supportive care and surgical intervention. In this study, we hypothesize that erythropoietin (Epo) could be protective against cell necrosis by increasing the levels of glutathione. This can be regulated by increasing the activity of system xC(-). This was demonstrated using intestinal epithelial cells (IEC-6) as a model system. S4-CPG and sulfasalazine pharmacologically inhibit xCT, which induced cell death...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28157330/low-threshold-multiexciton-optical-gain-in-colloidal-cdse-cdte-core-crown-type-ii-nanoplatelet-heterostructures
#15
Qiuyang Li, Zihao Xu, James R McBride, Tianquan Lian
Colloidal cadmium chalcogenide core/crown type-II nanoplatelet heterostructures, such as CdSe/CdTe, are promising materials for lasing and light-emitting applications. Their rational design and improvement requires the understanding of the nature of single- and multiexciton states. Using pump fluence and wavelength-dependent ultrafast transient absorption spectroscopy, we have identified three spatially and energetically distinct excitons (in the order of increasing energy): interface-localized charge transfer exciton (XCT, with electron in the CdSe core bound to the hole in the CdTe crown), and CdTe crown-localized XCdTe and CdSe core-localized XCdSe excitons...
March 28, 2017: ACS Nano
https://www.readbyqxmd.com/read/28105580/pixel-based-dxa-derived-structural-properties-strongly-correlate-with-pqct-measures-at-the-one-third-distal-femur-site
#16
Alexander M Baker, David W Wagner, B Jenny Kiratli, Gary S Beaupre
While bone mineral density has been traditionally used to quantify fracture risk for individuals with spinal cord injuries, recent studies are including engineering measurements such as section modulus and cross sectional moment of inertia. These are almost exclusively calculated by peripheral QCT scanners which, unlike DXA scanners, are rarely found in clinical settings. Using fifty-four fresh frozen femora, we developed and validated a pixel-by-pixel method to calculate engineering properties at the distal femur using a Hologic QDR-1000 W DXA scanner and compared them against similar parameters measured using a Stratec XCT-3000 peripheral QCT scanner...
May 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28086920/absence-of-system-xc-on-immune-cells-invading-the-central-nervous-system-alleviates-experimental-autoimmune-encephalitis
#17
Ellen Merckx, Giulia Albertini, Magdalena Paterka, Cathy Jensen, Philipp Albrecht, Michael Dietrich, Joeri Van Liefferinge, Eduard Bentea, Lise Verbruggen, Thomas Demuyser, Lauren Deneyer, Jan Lewerenz, Geert van Loo, Jacques De Keyser, Hideyo Sato, Pamela Maher, Axel Methner, Ann Massie
BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System xc(-) or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28073699/activation-of-nrf2-attenuates-carbonyl-stress-induced-by-methylglyoxal-in-human-neuroblastoma-cells-increase-in-gsh-levels-is-a-critical-event-for-the-detoxification-mechanism
#18
Shoichi Nishimoto, Shin Koike, Naho Inoue, Toshihiro Suzuki, Yuki Ogasawara
The present study focused on the methylglyoxal (MG) detoxification mechanism in neuroblastoma cells. The involvement of nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway as a defense response against the formation of MG-modified proteins, which is well-known evidence of carbonyl stress, was also examined. We found that MG treatment resulted in accumulation of modified proteins bearing the structure of advanced glycation end products (AGEs) derived from MG in SH-SY5Y cells...
January 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28070112/selenium-uptake-through-cystine-transporter-mediated-by-glutathione-conjugation
#19
Takao Tobe, Koji Ueda, Akira Aoki, Yoshinori Okamoto, Nakao Kojima, Hideto Jinno
Selenium (Se) is an essential trace element and is regarded as a protective agent against cancer. In particular, antioxidant effects of selenoenzymes contribute to cancer prevention. Se can also produce reactive oxygen species and, thereby, exert cancer-selective cytotoxicity. Selenodiglutathione (SDG) is a primary Se metabolite conjugated to two glutathione (GSH) moieties. SDG increases intracellular Se accumulation and is more toxic than selenous acid (H2SeO3), but the mechanisms for importing Se compounds into cells are not fully understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28057599/aspirin-plus-sorafenib-potentiates-cisplatin-cytotoxicity-in-resistant-head-and-neck-cancer-cells-through-xct-inhibition
#20
Jong-Lyel Roh, Eun Hye Kim, Hyejin Jang, Daiha Shin
The nonsteroidal anti-inflammatory drug aspirin and the multikinase inhibitor sorafenib have both shown experimental and clinical anticancer activities. The present study investigated whether aspirin and sorafenib synergize to potentiate cisplatin treatment in resistant head and neck cancer (HNC) cells. The effects of aspirin, sorafenib and cisplatin, and combinations thereof were assessed by measuring cell viability, death, glutathione (GSH) and reactive oxygen species (ROS) levels, protein and mRNA expression, genetic inhibition and overexpression of cystine-glutamate antiporter (xCT) and tumor xenograft mouse models...
March 2017: Free Radical Biology & Medicine
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