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https://www.readbyqxmd.com/read/28086920/absence-of-system-xc-on-immune-cells-invading-the-central-nervous-system-alleviates-experimental-autoimmune-encephalitis
#1
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
#2
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
#3
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
#4
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...
January 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28046525/su-c-207a-03-development-of-proton-ct-imaging-system-using-thick-scintillator-and-ccd-camera
#5
S Tanaka, T Nishio, K Matsushita, M Tsuneda, S Kabuki, M Uesaka
PURPOSE: In the treatment planning of proton therapy, Water Equivalent Length (WEL), which is the parameter for the calculation of dose and the range of proton, is derived by X-ray CT (xCT) image and xCT-WEL conversion. However, about a few percent error in the accuracy of proton range calculation through this conversion has been reported. The purpose of this study is to construct a proton CT (pCT) imaging system for an evaluation of the error. METHODS: The pCT imaging system was constructed with a thick scintillator and a cooled CCD camera, which acquires the two-dimensional image of integrated value of the scintillation light toward the beam direction...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28024798/zonisamide-attenuates-lactacystin-induced-parkinsonism-in-mice-without-affecting-system-xc
#6
Eduard Bentea, Joeri Van Liefferinge, Lise Verbruggen, Katleen Martens, Sho Kobayashi, Lauren Deneyer, Thomas Demuyser, Giulia Albertini, Katrien Maes, Hideyo Sato, Ilse Smolders, Jan Lewerenz, Ann Massie
Zonisamide (ZNS), an anticonvulsant drug exhibiting symptomatic effects in Parkinson's disease (PD), was recently reported to exert neuroprotection in rodent models. One of the proposed neuroprotective mechanisms involves increased protein expression of xCT, the specific subunit of the cystine/glutamate antiporter system xc(-), inducing glutathione (GSH) synthesis. Here, we investigated the outcome of ZNS treatment in a mouse model of PD based on intranigral proteasome inhibition, and whether the observed effects would be mediated by system xc(-)...
December 24, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28018725/region-based-diffuse-optical-tomography-with-registered-atlas-in-vivo-acquisition-of-mouse-optical-properties
#7
Wenbo Wan, Yihan Wang, Jin Qi, Lingling Liu, Wenjuan Ma, Jiao Li, Limin Zhang, Zhongxing Zhou, Huijuan Zhao, Feng Gao
The reconstruction quality in the model-based optical tomography modalities can greatly benefit from a priori information of accurate tissue optical properties, which are difficult to be obtained in vivo with a conventional diffuse optical tomography (DOT) system alone. One of the solutions is to apply a priori anatomical structures obtained with anatomical imaging systems such as X-ray computed tomography (XCT) to constrain the reconstruction process of DOT. However, since X-ray offers low soft-tissue contrast, segmentation of abdominal organs from sole XCT images can be problematic...
December 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27993695/effects-of-orally-administered-augmentin-on-glutamate-transporter-1-cystine-glutamate-exchanger-expression-and-ethanol-intake-in-alcohol-preferring-rats
#8
Alqassem Y Hakami, Fahad S Alshehri, Yusuf S Althobaiti, Youssef Sari
Alcohol dependence is associated with deficits in glutamate uptake and impairment of glutamate homeostasis in different brain reward regions. Glutamate transporter subtype 1 (GLT-1), cystine-glutamate exchanger (xCT) and glutamate/aspartate transporter (GLAST) are one of the key players in regulating extracellular glutamate concentration in the brain. Parenteral treatment with ceftriaxone, β-lactam antibiotic, has been reported to attenuate ethanol consumption and reinstatement to cocaine-seeking behavior, in part, by restoring the expression of GLT-1 and xCT in mesocorticolimbic brain regions in rats...
December 16, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27940248/integrin-targeted-hybrid-fluorescence-molecular-tomography-x-ray-computed-tomography-for-imaging-tumor-progression-and-early-response-in-non-small-cell-lung-cancer
#9
Xiaopeng Ma, Valerie Phi Van, Melanie A Kimm, Jaya Prakash, Horst Kessler, Katja Kosanke, Annette Feuchtinger, Michaela Aichler, Aayush Gupta, Ernst J Rummeny, Michel Eisenblätter, Jens Siveke, Axel K Walch, Rickmer Braren, Vasilis Ntziachristos, Moritz Wildgruber
Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF) probe...
December 7, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27888396/effects-of-administered-ethanol-and-methamphetamine-on-glial-glutamate-transporters-in-rat-striatum-and-hippocampus
#10
Fahad S Alshehri, Yusuf S Althobaiti, Youssef Sari
Exposure to ethanol (EtOH) or methamphetamine (MA) can lead to increase in extracellular glutamate concentration in the brain. Although studies from ours showed the effects of EtOH exposure on key glial glutamate transporters, little is known about the effects of sequential exposure to EtOH and MA or MA alone on certain glial glutamate transporters. In this study, we investigated the effects of sequential exposure to EtOH and MA on the expression of the major glutamate transporters, glutamate transporter 1 (GLT-1), as well as cystine/glutamate antiporter (xCT) and glutamate aspartate transporter (GLAST) in striatum and hippocampus...
November 25, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27869804/systemic-depletion-of-l-cyst-e-ine-with-cyst-e-inase-increases-reactive-oxygen-species-and-suppresses-tumor-growth
#11
Shira L Cramer, Achinto Saha, Jinyun Liu, Surendar Tadi, Stefano Tiziani, Wupeng Yan, Kendra Triplett, Candice Lamb, Susan E Alters, Scott Rowlinson, Yan Jessie Zhang, Michael J Keating, Peng Huang, John DiGiovanni, George Georgiou, Everett Stone
Cancer cells experience higher oxidative stress from reactive oxygen species (ROS) than do non-malignant cells because of genetic alterations and abnormal growth; as a result, maintenance of the antioxidant glutathione (GSH) is essential for their survival and proliferation. Under conditions of elevated ROS, endogenous L-cysteine (L-Cys) production is insufficient for GSH synthesis. This necessitates uptake of L-Cys that is predominantly in its disulfide form, L-cystine (CSSC), via the xCT(-) transporter. We show that administration of an engineered and pharmacologically optimized human cyst(e)inase enzyme mediates sustained depletion of the extracellular L-Cys and CSSC pool in mice and non-human primates...
January 2017: Nature Medicine
https://www.readbyqxmd.com/read/27821299/biomarkers-related-with-seizure-risk-in-glioma-patients-a-systematic-review
#12
REVIEW
Xing-Wang Zhou, Xiang Wang, Yuan Yang, Jie-Wen Luo, Hui Dong, Yan-Hui Liu, Qing Mao
Increasing evidence indicates that genetic biomarkers play important roles in the development of glioma-associated seizures. Thus, we performed a systematic review to summarise biomarkers that are associated with seizures in glioma patients. An electronic literature search of public databases (PubMed, Embase and Medline) was performed using the keywords glioma, seizure and epilepsy. A totall of 26 eligible studies with 2224 cases were included in this systematic review of publications to 20 June, 2016. Genetic biomarkers such as isocitrate dehydrogenase 1 (IDH1) mutations, low expression of excitatory amino acid transporter 2 (EAAT2), high xCT expression, overexpression of adenosine kinase (ADK) and low expression of very large G-protein-coupled receptor-1 (VLGR1) are primarily involved in synaptic transmission, whereas BRAF mutations, epidermal growth factor receptor (EGFR) amplification, miR-196b expression and low ki-67 expression are associated with regulation of cell proliferation...
December 2016: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/27801527/hif-1%C3%AE-triggers-long-lasting-glutamate-excitotoxicity-via-system-xc-in-cerebral-ischaemia-reperfusion
#13
Chia-Hung Hsieh, Yu-Jung Lin, Wei-Ling Chen, Yen-Chih Huang, Chi-Wei Chang, Fu-Chou Cheng, Ren-Shyan Liu, Woei-Cherng Shyu
Hypoxia-inducible factor 1α (HIF-1α) controls many genes involved in physiological and pathological processes. However, its roles in glutamatergic transmission and excitotoxicity are unclear. Here, we proposed that HIF-1α might contribute to glutamate-mediated excitotoxicity during cerebral ischaemia-reperfusion (CIR) and investigated its molecular mechanism. We showed that an HIF-1α conditional knockout mouse displayed an inhibition in CIR-induced elevation of extracellular glutamate and N-methyl-d-aspartate receptor (NMDAR) activation...
November 1, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27789715/18f-5-fluoro-aminosuberic-acid-fasu-as-a-potential-tracer-to-gauge-oxidative-stress-in-breast-cancer-models
#14
Hua Yang, Silvia Jenni, Milena Colovic, Helen Merkens, Carlee Poleschuk, Isabel Rodrigo, Qing Miao, Bruce F Johnson, Michael J Rishel, Vesna Sossi, Jack M Webster, François Bénard, Paul Schaffer
: The cystine transporter (system xC-) is an antiporter of cystine and glutamate. It has relatively low basal expression in most tissues and becomes upregulated in cells under oxidative stress (OS) as one of the genes expressed in response to the antioxidant response element (ARE) promoter. We have developed (18)F-5-fluoro-aminosuberic acid (FASu), a Positron Emission Tomography (PET) tracer that targets system xC-. The goal of this study was to evaluate the suitability of (18)F-FASu as a specific gauge for system xC- activity in vivo and its potential usefulness for breast cancer imaging...
October 27, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27713684/effects-of-ceftriaxone-on-glial-glutamate-transporters-in-wistar-rats-administered-sequential-ethanol-and-methamphetamine
#15
Yusuf S Althobaiti, Fahad S Alshehri, Atiah H Almalki, Youssef Sari
Methamphetamine (METH) is one of the psychostimulants that is co-abused with ethanol. Repeated exposure to high dose of METH has been shown to cause increases in extracellular glutamate concentration. We have recently reported that ethanol exposure can also increase the extracellular glutamate concentration and downregulate the expression of glutamate transporter subtype 1 (GLT-1). GLT-1 is a glial transporter that regulates the majority of extracellular glutamate. A Wistar rat model of METH and ethanol co-abuse was used to examine the expression of GLT-1 as well as other glutamate transporters such as cystine/glutamate exchanger (xCT) and glutamate aspartate transporter (GLAST)...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27708226/mitochondrial-dysfunction-enhances-cisplatin-resistance-in-human-gastric-cancer-cells-via-the-ros-activated-gcn2-eif2%C3%AE-atf4-xct-pathway
#16
Sheng-Fan Wang, Meng-Shian Chen, Yueh-Ching Chou, Yune-Fang Ueng, Pen-Hui Yin, Tien-Shun Yeh, Hsin-Chen Lee
Mitochondrial DNA mutations and defects in mitochondrial enzymes have been identified in gastric cancers, and they might contribute to cancer progression. In previous studies, mitochondrial dysfunction was induced by oligomycin-enhanced chemoresistance to cisplatin. Herein, we dissected the regulatory mechanism for mitochondrial dysfunction-enhanced cisplatin resistance in human gastric cancer cells. Repeated cisplatin treatment-induced cisplatin-resistant cells exhibited high SLC7A11 (xCT) expression, and xCT inhibitors (sulfasalazine or erastin), xCT siRNA, or a GSH synthesis inhibitor (buthionine sulphoximine, BSO) could sensitize these cells to cisplatin...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27658422/increased-expression-of-system-xc-in-glioblastoma-confers-an-altered-metabolic-state-and-temozolomide-resistance
#17
Monika D Polewski, Rosyli F Reveron-Thornton, Gregory A Cherryholmes, Georgi K Marinov, Kaniel Cassady, Karen S Aboody
: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in adults. Several studies have shown that glioma cells upregulate the expression of xCT (SLC7A11), the catalytic subunit of system xc(-), a transporter involved in cystine import, that modulates glutathione production and glioma growth. However, the role of system xc(-) in regulating the sensitivity of glioma cells to chemotherapy is currently debated. Inhibiting system xc(-) with sulfasalazine decreased glioma growth and survival via redox modulation, and use of the chemotherapeutic agent temozolomide together with sulfasalazine had a synergistic effect on cell killing...
December 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27642492/differential-regulation-of-the-extracellular-cysteine-cystine-redox-state-ehcyss-by-lung-fibroblasts-from-young-and-old-mice
#18
Walter H Watson, Tom J Burke, Igor N Zelko, Edilson Torres-González, Jeffrey D Ritzenthaler, Jesse Roman
Aging is associated with progressive oxidation of plasma cysteine (Cys)/cystine (CySS) redox state, expressed as EhCySS. Cultured cells condition their media to reproduce physiological EhCySS, but it is unknown whether aged cells produce a more oxidized extracellular environment reflective of that seen in vivo. In the current study, we isolated primary lung fibroblasts from young and old female mice and measured the media EhCySS before and after challenge with Cys or CySS. We also measured expression of genes related to redox regulation and fibroblast function...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27612422/temozolomide-toxicity-operates-in-a-xct-slc7a11-dependent-manner-and-is-fostered-by-ferroptosis
#19
REVIEW
Tina Sehm, Manfred Rauh, Kurt Wiendieck, Michael Buchfelder, IIker Y Eyüpoglu, Nicolai E Savaskan
The glutamate exchanger xCT (SLC7a11) is causally linked with the malignancy grade of brain tumors and represents a key player in glutamate, cystine and glutathione metabolism. Although blocking xCT is not cytotoxic for brain tumors, xCT inhibition disrupts the neurodegenerative and microenvironment-toxifying activity of gliomas. Here, we report on the use of various xCT inhibitors as single modal drugs and in combination with the autophagy-inducing standard chemotherapeutic agent temozolomide (Temodal/Temcad®, TMZ)...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27594594/fluorescence-based-measurement-of-cystine-uptake-through-xct-shows-requirement-for-ros-detoxification-in-activated-lymphocytes
#20
Peter J Siska, Bumki Kim, Xiangming Ji, Megan D Hoeksema, Pierre P Massion, Kathryn E Beckermann, Jianli Wu, Jen-Tsan Chi, Jiyong Hong, Jeffrey C Rathmell
T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide sufficient and necessary intracellular metabolites, uptake of extracellular nutrients increases sharply with metabolic re-programming. One result of increased metabolic activity can be reactive oxygen species (ROS), which can be toxic when accumulated in excess...
November 2016: Journal of Immunological Methods
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