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system xc

Hossein Gholizadeh, Edward D Lemaire, Emily H Sinitski
BACKGROUND: People with lower limb amputation may experience walking limitations on slopes because of missg 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...
July 26, 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...
July 21, 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...
July 18, 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
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 a variety of tests and systems have been FDA-cleared for use in the United States. We performed a retrospective study to compare the Cepheid Xpress Flu/RSV assay to the Xpert Flu/RSV XC assay, using laboratory-developed tests (LDTs) as the reference method. The Xpress assay was 100% accurate as compared to the LDTs, while the Xpert Flu/RSV XC was 96.0% accurate. The Xpress test was determined to be faster and more sensitive than the XC...
May 16, 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
Xiao-Hong Li, Chen Li, Yiting Tang, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Ting Huang, Feiyan Zhao, Cai-Xia Hao, Dan-Dan Feng, Jian-Ping Xu, Jianzhong Han, Siyuan Tang, Wei Liu, Shaojie Yue, Zi-Qiang 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...
May 3, 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
Martin P Bircher, Ursula Rothlisberger
Linear-response time-dependent density functional theory (LR-TD-DFT) has become a valuable tool in the calculation of excited states of molecules of various sizes. However, standard generalized-gradient approximation and hybrid exchange-correlation (xc) functionals often fail to correctly predict charge-transfer (CT) excitations with low orbital overlap, thus limiting the scope of the method. The Coulomb-attenuation method (CAM) in the form of the CAM-B3LYP functional has been shown to reliably remedy this problem in many CT systems, making accurate predictions possible...
June 12, 2018: Journal of Chemical Theory and Computation
Michael M Gaschler, Alexander A Andia, Hengrui Liu, Joleen M Csuka, Brisa Hurlocker, Christopher A Vaiana, Daniel W Heindel, Dylan S Zuckerman, Pieter H Bos, Eduard Reznik, Ling F Ye, Yulia Y Tyurina, Annie J Lin, Mikhail S Shchepinov, Amy Y Chan, Eveliz Peguero-Pereira, Maksim A Fomich, Jacob D Daniels, Andrei V Bekish, Vadim V Shmanai, Valerian E Kagan, Lara K Mahal, K A Woerpel, Brent R Stockwell
Ferroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2 . We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc - or directly target the reducing enzyme GPX4, as do erastin and RSL3, respectively, nor does it deplete GPX4 protein, as does FIN56...
May 2018: Nature Chemical Biology
Carly N Logan, Amber L LaCrosse, Lori A Knackstedt
Cocaine use disorder is a chronically relapsing disease without FDA-approved treatments. Using a rodent model of cocaine relapse, we and others have previously demonstrated that the beta-lactam antibiotic ceftriaxone attenuates cue- and cocaine-primed reinstatement of cocaine-seeking. Ceftriaxone restores cocaine-induced deficits in both system xc- and GLT-1 expression and function in the nucleus accumbens core (NAc). We recently demonstrated that restoration of GLT-1 expression in the NAc is necessary for ceftriaxone to attenuate reinstatement of cocaine-seeking...
June 2018: Neuropharmacology
Andreas Heßelmann
Intermolecular interaction energies have been calculated by symmetry-adapted perturbation theory based on density functional theory monomer properties (DFT-SAPT) employing response functions from time-dependent exact-exchange (TDEXX) kernels. Combined with a new asymptotic correction scheme for the exchange-correlation (xc) potentials of the monomers, which is similar in its performance to standard asymptotic correction methods, it is shown that this DFT-SAPT[TDEXX] method delivers highly accurate intermolecular interaction energies for the S22, S66, and IonHB benchmark databases by Hobza et al...
April 10, 2018: Journal of Chemical Theory and Computation
M Moreno, A Zacarias, A Porzel, L Velasquez, G Gonzalez, M Alegría-Arcos, F Gonzalez-Nilo, E K U Gross
Emerging and re-emerging epidemic diseases pose an ongoing threat to global health. Currently, Enterobactin and Enterobactin derivatives have gained interest, owing to their potential application in the pharmaceutical field. As it is known [J. Am. Chem. Soc (1979) 101, 20, 6097-6104], Enterobactin (H6 EB) is an efficient iron carrier synthesized and secreted by many microbial species. In order to facilitate the elucidation of enterobactin and its analogues, here we propose the creation of a H6 EB standard set using Density Functional Theory Infrared (IR) and NMR spectra...
June 5, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Raul Carpi-Santos, Karin C Calaza
Nrf2 (nuclear factor erythroid 2-related factor 2), a transcription factor that controls expression of several proteins that are related to cellular antioxidant capacity, such as the subunit xCT of the system xc - , is dysregulated in diabetes. Recently, it was described that system xc - is decreased in the retina after 3 weeks of diabetes. So, in the present work, the temporal relationship between xCT and Nrf2 in the retina of diabetic animals was investigated. Diabetes was induced in male Wistar rats (200 g) by a single injection of streptozotocin, and retinas were collected after 1, 2, and 6 months of diabetes induction...
February 27, 2018: Molecular Neurobiology
Aileen Hoehne, Michelle L James, Israt S Alam, John A Ronald, Bernadette Schneider, Aloma D'Souza, Timothy H Witney, Lauren E Andrews, Haley C Cropper, Deepak Behera, Gayatri Gowrishankar, Zhaoqing Ding, Tony Wyss-Coray, Frederick T Chin, Sandip Biswal, Sanjiv S Gambhir
BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18 F]fluoropropyl)-L-glutamate ([18 F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55 ) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin...
February 22, 2018: Journal of Neuroinflammation
Jan Hermann, Alexandre Tkatchenko
Short-range correlations in motion of electrons in matter are captured well by semilocal exchange-correlation (XC) functionals in density functional theory (DFT), but long-range correlations are neglected in such models and must be treated by van der Waals (vdW) dispersion methods. Whereas the effective range of distances at which fluctuations are correlated is usually explicit in the vdW models, the complementary range of semilocal functionals can be observed only implicitly, requiring an introduction of empirical damping functions to couple the semilocal and nonlocal contributions to the XC energy...
March 13, 2018: Journal of Chemical Theory and Computation
Nana Kobayashi, Shogo Okazaki, Oltea Sampetrean, Junichiro Irie, Hiroshi Itoh, Hideyuki Saya
CD44 variant (CD44v) contributes to cancer stemness by stabilizing the xCT subunit of system xc(-) and thereby promoting its glutamate-cystine antiporter activity. CD44 has also been implicated in autoimmune insulitis and inflammation in diabetic islets, but whether CD44v regulates insulin secretion has remained unclear. Here we show that CD44v inhibits insulin secretion by attenuating amino acid transport mediated by the L-type amino acid transporter LAT1. CD44v expression level was inversely related to insulin content in islets of normal and diabetic model mice...
February 12, 2018: Scientific Reports
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