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system xc

Milena Čolović, Etienne Rousseau, Zhengxing Zhang, Joseph Lau, Chengcheng Zhang, Hsiou-Ting Kuo, Hua Yang, Paul Schaffer, François Bénard, Kuo-Shyan Lin
In this study, we synthesized 18 F-ASu-BF3 , a close boramino acid analog of 5-[18 F]fluoro-aminosuberic acid (18 F-ASu), via 18 F-19 F isotope exchange reaction and evaluated its potential for imaging with positron emission tomography (PET). 18 F-ASu-BF3 was stable in mouse plasma and taken up into PC3 prostate cancer cells via the system xC - amino acid transporter. The continuous use of isoflurane for anesthesia during dynamic imaging acquisition slowed down the excretion of 18 F-ASu-BF3 and enabled visualization of PC3 tumor xenografts in mice...
June 8, 2018: Bioorganic & Medicinal Chemistry Letters
Carla Garza-Lombó, Pavel Petrosyan, Miguel Tapia-Rodríguez, Cesar Valdovinos-Flores, María E Gonsebatt
Glutathione (GSH) is an essential component of intracellular antioxidant systems that plays a primordial role in the protection of cells against oxidative stress, maintaining redox homeostasis and xenobiotic detoxification. GSH synthesis in the brain is limited by the availability of cysteine and glutamate. Cystine, the disulfide form of cysteine is transported into endothelial cells of the blood-brain barrier (BBB) and astrocytes via the system xc - , which is composed of xCT and the heavy chain of 4F2 cell surface antigen (4F2hc)...
October 6, 2018: Neurochemistry International
Kentaro Suina, Kenji Tsuchihashi, Juntaro Yamasaki, Shohei Kamenori, Subaru Shintani, Yuki Hirata, Shogo Okazaki, Oltea Sampetrean, Eishi Baba, Koichi Akashi, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kazuhisa Takahashi, Hideyuki Saya, Osamu Nagano
Autocrine and paracrine factors, including glutamate and epidermal growth factor (EGF), are potent inducers of brain tumor cell invasion, a pathological hallmark of malignant gliomas. System xc(-) consists of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. We previously showed that the EGF receptor (EGFR) interacts with xCT and thereby promotes the activity of system xc(-) in a kinase-independent manner, resulting in enhanced glutamate release, in glioma cells...
October 9, 2018: Cancer Science
Min-Wei Huang, Yu-Jung Lin, Chi-Wei Chang, Fu-Ju Lei, En-Peng Ho, Ren-Shyan Liu, Woei-Cherng Shyu, Chia-Hung Hsieh
Rationale: Although molecular investigations of regulator of G-protein signaling 4 (RGS4) alterations in schizophrenia patients yielded partially inconsistent findings, the previous studies suggested that RGS4 is both a positional and functional candidate gene for schizophrenia and is significantly decreased in the prefrontal cortex. However, the exact role of RGS4 in the pathophysiology of schizophrenia is unclear. Moreover, a whole genome transcription profile study showed the possibility of RGS4-regulated expression of SLC7A11(xCT), a component of cysteine/glutamate transporter or system xc - ...
2018: Theranostics
Roberta Mastrantonio, Veronica D'Ezio, Marco Colasanti, Tiziana Persichini
HIV-associated neurocognitive disorders (HANDs) affect a large part of HIV-infected patients, despite highly active antiretroviral therapy. HANDs occur in the absence of a direct infection of neurons. Nevertheless, viral proteins (e.g., Tat) are capable to cause neuronal dysfunction via oxidative stress, but the cellular pathways leading to HANDs are not yet fully defined. Here, we investigated the effects of Tat on Nrf2-mediated antioxidant response and system xc - expression in U373 human astroglial cells...
September 12, 2018: Molecular Neurobiology
Reham Mokhtar Aman, Irhan Ibrahim Abu Hashim, Mahasen Mohamed Meshali
Apocynin (APO), a specific NADPH oxidase inhibitor, is a bioactive phytochemical that exhibits versatile pharmacological activities. However, its rapid elimination and poor bioavailability represent great challenges to pharmaceutical scientists. Accordingly, novel chitosan-based APO-loaded solid lipid nanoparticles (CS,APO - loaded SLNS ) were developed to address such obstacles. A full 24 factorial design of experiment approach was employed to evaluate the individual and combined effect of critical process parameters namely; the amount of glycerol tristearate (GTS, XA ) and sucrose mono palmitate (SMP, XB ) as well as the concentration of chitosan (CS, XC ) and polyvinyl alcohol (PVA, XD ), on different critical quality attributes...
November 1, 2018: European Journal of Pharmaceutical Sciences
Rui Kang, Shan Zhu, Herbert J Zeh, Daniel J Klionsky, Daolin Tang
Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferroptosis through the regulation of activity of the cysteine and glutamate antiporter system xc - in cancer cells. BECN1-dependent autophagy requires the formation of the BECN1-containing class III phosphatidylinositol 3-kinase (PtdIns3K) complex, whereas BECN1-dependent ferroptosis requires the formation of a BECN1-SLC7A11 complex...
September 6, 2018: Autophagy
Christina Gates, Donald S Backos, Philip Reigan, Hye Jin Kang, Chris Koerner, Joseph Mirzaei, N R Natale
Isoxazolo[3,4-d] pyridazinones ([3,4-d]s) are selective positive modulators of the metabotropic glutamate receptors (mGluRs) subtypes 2 and 4, with no functional cross reactivity at mGluR1a , mGLuR5 or mGluR8 . Modest binding for two of the [3,4-d]s is observed at the allosteric fenobam mGluR5 site, but not sufficient to translate into a functional effect. The structure activity relationship (SAR) for mGluR2 and mGluR4 are distinct: the compounds which select for mGluR2 all contain fluorine on the N-6 aryl group...
September 15, 2018: Bioorganic & Medicinal Chemistry
Ran Zhang, Juan P Cruz-Bastida, Daniel Gomez-Cardona, John W Hayes, Ke Li, Guang-Hong Chen
PURPOSE: The CT number accuracy, that is, CT number bias, plays an important role in clinical diagnosis. When strategies to reduce radiation dose are discussed, it is important to make sure that the CT number bias is controlled within an acceptable range. The purpose of this paper was to investigate the dependence of CT number bias on radiation dose level and on image contrast (i.e., the difference in CT number between the ROI and the background) in Computed Tomography (CT). METHODS: A lesion-background model was introduced to theoretically study how the CT number bias changes with radiation exposure level and with CT number contrast when a simple linear reconstruction algorithm such as filtered backprojection (FBP) is used...
August 13, 2018: Medical Physics
Hossein Gholizadeh, Edward D Lemaire, Emily H Sinitski
BACKGROUND: People with lower limb amputation may experience walking limitations on slopes because of missing musculoskeletal and neuromuscular systems. Elevated vacuum suspension could benefit transtibial amputee gait for slope walking, but research is lacking to inform clinical practice. METHODS: Twelve people with unilateral transtibial amputation were fitted with the Unity elevated vacuum suspension system (Össur) and Pro-Flex XC foot. 3D motion analysis was performed for 7° incline, 7° decline, and level walking within a CAREN-Extended system virtual Park environment...
September 2018: Gait & Posture
Xinxin Song, Shan Zhu, Pan Chen, Wen Hou, Qirong Wen, Jiao Liu, Yangchun Xie, Jinbao Liu, Daniel J Klionsky, Guido Kroemer, Michael T Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
Ferroptosis is a form of regulated cell death triggered by lipid peroxidation after inhibition of the cystine/glutamate antiporter system Xc - . However, key regulators of system Xc - activity in ferroptosis remain undefined. Here, we show that BECN1 plays a hitherto unsuspected role in promoting ferroptosis through directly blocking system Xc- activity via binding to its core component, SLC7A11 (solute carrier family 7 member 11). Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system Xc - inhibitors (e...
August 6, 2018: Current Biology: CB
Øyvind Karlsson, Matthias Gilgien, Øyvind N Gløersen, Bjarne Rud, Thomas Losnegard
Purpose: In this study wearable global navigation satellite system units were used on athletes to investigate pacing patterns by describing exercise intensities in flat and uphill terrain during a simulated cross-country ski race. Methods: Eight well-trained male skiers (age: 23.0 ± 4.8 years, height: 183.8 ± 6.8 cm, weight: 77.1 ± 6.1 kg, VO2peak : 73 ± 5 mL⋅kg-1 ⋅min-1 ) completed a 13.5-km individual time trial outdoors and a standardized indoor treadmill protocol on roller skis. Positional data were recorded during the time trial using a differential global navigation satellite system to calculate external workloads in flat and uphill terrain...
2018: Frontiers in Physiology
Huan Gao, Yuansong Bai, Yuanyuan Jia, Yanan Zhao, Rui Kang, Daolin Tang, Enyong Dai
Ferroptosis is a form of regulated cell death resulting from iron accumulation and lipid peroxidation. While impaired ferroptosis is tightly linked to human diseases and conditions, the mechanism and regulation of ferroptosis remain largely unknown. Here, we demonstrate that STAT3 is a positive regulator of ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cell lines. Activation of the MAPK/ERK pathway, but not inhibition of system Xc- , was required for STAT3 activation during erastin-induced ferroptosis...
September 10, 2018: Biochemical and Biophysical Research Communications
Yun Sun, Yingfeng Zheng, Chunxiao Wang, Yizhi Liu
Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells...
July 9, 2018: Cell Death & Disease
Jack L Arbiser, Michael Y Bonner, Nicole Ward, Justin Elsey, Shikha Rao
BACKGROUND: A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes...
May 28, 2018: Biochimica et biophysica acta. General subjects
Sho Kobayashi, Shinji Hamashima, Takujiro Homma, Mami Sato, Ryosuke Kusumi, Shiro Bannai, Junichi Fujii, Hideyo Sato
The amino acid transport system xc - is important for maintaining intracellular glutathione levels and extracellular redox balance. The main component of system xc - , xCT, is strongly induced by various stimuli, including oxidative stress and bacterial lipopolysaccharides (LPS) in macrophages. In the present study, we investigated the production of nitric oxide by LPS-stimulated mouse peritoneal macrophages isolated from both xCT-deficient and wild-type mice. After culturing macrophages in the presence of LPS for 24-48 h, nitrite levels in the medium of xCT-deficient macrophages were significantly decreased compared to that of wild-type cells...
May 21, 2018: Nitric Oxide: Biology and Chemistry
Elena B Popowitch, Melissa B Miller
Molecular diagnostics for influenza and respiratory syncytial virus (RSV) have become commonplace, and various tests and systems have been cleared by the FDA for use in the United States. We performed a retrospective study to compare the Cepheid Xpress Flu/RSV assay with the Xpert Flu/RSV XC assay, using laboratory-developed tests (LDTs) as the reference method. The Xpress assay was 100% accurate compared to LDTs, whereas the Xpert Flu/RSV XC assay was 96.0% accurate. The Xpress test was determined to be faster and more sensitive than the XC assay...
August 2018: Journal of Clinical Microbiology
Tanya Miladinovic, Robert G Ungard, Katja Linher-Melville, Snezana Popovic, Gurmit Singh
Breast cancer cells release the signalling molecule glutamate via the system xC - antiporter, which is upregulated to exchange extracellular cystine for intracellular glutamate to protect against oxidative stress. Here, we demonstrate that this antiporter is functionally influenced by the actions of the neurotrophin nerve growth factor on its cognate receptor tyrosine kinase, TrkA, and that inhibiting this complex may reduce cancer-induced bone pain via its downstream actions on xCT, the functional subunit of system xC - ...
January 2018: Molecular Pain
Xiaohong Li, Chen Li, Yiting Tang, Yanhong Huang, Qingmei Cheng, Xiaoting Huang, Feiyan Zhao, Caixia Hao, Dandan Feng, Jianping Xu, Jianzhong Han, Siyuan Tang, Wei Liu, Shaojie Yue, Ziqiang Luo
Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc - in vitro...
September 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Giulia Albertini, Lauren Deneyer, Sigrid Ottestad-Hansen, Yun Zhou, Gamze Ates, Laura Walrave, Thomas Demuyser, Eduard Bentea, Hideyo Sato, Dimitri De Bundel, Niels C Danbolt, Ann Massie, Ilse Smolders
The communication between the immune and central nervous system (CNS) is affected in many neurological disorders. Peripheral injections of the endotoxin lipopolysaccharide (LPS) are widely used to study this communication: an LPS challenge leads to a biphasic syndrome that starts with acute sickness and is followed by persistent brain inflammation and chronic behavioral alterations such as depressive-like symptoms. In vitro, the response to LPS treatment has been shown to involve enhanced expression of system xc-...
April 25, 2018: Glia
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