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https://www.readbyqxmd.com/read/29792932/cystine-glutamate-transporter-system-x-c-is-involved-in-nitric-oxide-production-in-mouse-peritoneal-macrophages
#1
Sho Kobayashi, Shinji Hamashima, Takujiro Homma, Mami Sato, Ryosuke Kusumi, Shiro Bannai, Junich 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
https://www.readbyqxmd.com/read/29789716/xct-slc7a11-mediated-metabolic-reprogramming-promotes-non-small-cell-lung-cancer-progression
#2
Xiangming Ji, Jun Qian, S M Jamshedur Rahman, Peter J Siska, Yong Zou, Bradford K Harris, Megan D Hoeksema, Irina A Trenary, Chen Heidi, Rosana Eisenberg, Jeffrey C Rathmell, Jamey D Young, Pierre P Massion
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29785244/more-than-just-an-immunosuppressant-the-emerging-role-of-fty720-as-a-novel-inducer-of-ros-and-apoptosis
#3
REVIEW
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29781387/estrogen-related-receptor-alpha-triggers-the-migration-and-invasion-of-endometrial-cancer-cells-via-up-regulation-of-tgfb1
#4
Xiumin Huang, Xuelian Wang, Jing Shang, Zhiqin Zhaang, Binbin Cui, Yanzhen Lin, Ying Yang, Youyi Song, Shengnan Yu, Junjie Xia
Estrogenic signals have been suggested to be important for the tumorigenesis and progression of endometrial cancer (EC) cells. Our present data showed that estrogen related receptor alpha (ERRα), while not ERRβ or ERRγ, was significantly elevated in EC cells and tissues when compared to their controls. Targeted inhibition of ERRα by siRNA or its inverse agonist XCT-790 can suppress the migration and invasion of EC cells. Both si-ERRα and XCT-790 decreased the expression of transforming growth factor-beta (TGF-β)...
May 21, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29778238/interplay-between-estrogen-related-receptors-and-steroidogenesis-controlling-molecules-in-adrenals-in-vivo-and-in-vitro-study
#5
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29764521/amino-acid-transporter-slc7a11-xct-at-the-crossroads-of-regulating-redox-homeostasis-and-nutrient-dependency-of-cancer
#6
REVIEW
Pranavi Koppula, Yilei Zhang, Li Zhuang, Boyi Gan
Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs, and to maintain redox homeostasis. One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT). SLC7A11 promotes cystine uptake and glutathione biosynthesis, resulting in protection from oxidative stress and ferroptotic cell death. Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells...
April 25, 2018: Cancer communications
https://www.readbyqxmd.com/read/29761734/functional-effects-of-trka-inhibition-on-system-x-c-mediated-glutamate-release-and-cancer-induced-bone-pain
#7
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
https://www.readbyqxmd.com/read/29753887/peri-adolescent-drinking-of-ethanol-and-or-nicotine-modulates-astroglial-glutamate-transporters-and-metabotropic-glutamate-receptor-1-in-female-alcohol-preferring-rats
#8
Fawaz Alasmari, Richard L Bell, P S S Rao, Alaa M Hammad, Youssef Sari
Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicated that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression...
May 10, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29715172/how-hedstrom-files-fail-during-clinical-use-a-retrieval-study-based-on-sem-optical-microscopy-and-micro-xct-analysis
#9
Spiros Zinelis, Youssef S Al Jabbari
This study was conducted to evaluate the failure mechanism of clinically failed Hedstrom (H)-files. Discarded H-files (n=160) from #8 to #40 ISO sizes were collected from different dental clinics. Retrieved files were classified according to their macroscopic appearance and they were investigated under scanning electron microscopy (SEM) and X-ray micro-computed tomography (mXCT). Then the files were embedded in resin along their longitudinal axis and after metallographic grinding and polishing, studied under an incident light microscope...
May 1, 2018: Biomedizinische Technik. Biomedical Engineering
https://www.readbyqxmd.com/read/29702192/pseudolaric-acid-b-triggers-ferroptosis-in-glioma-cells-via-activation-of-nox4-and-inhibition-of-xct
#10
Zongqi Wang, Ye Ding, Xuanzhong Wang, Shan Lu, Chongcheng Wang, Chuan He, Lei Wang, Meihua Piao, Guangfan Chi, Yinan Luo, Pengfei Ge
Ferroptosis is a form of programmed cell death decided by iron-dependent lipid peroxidation, but its role in glioma cell death remains unclear. In this study, we found Pseudolaric acid B (PAB) inhibited the viabilities of glioma cells in vitro and in vivo, which was accompanied by abnormal increases of intracellular ferrous iron, H2 O2 and lipid peroxidation, as well as depletion of GSH and cysteine. In vitro studies revealed that the lipid peroxidation and the cell death caused by PAB were both inhibited by iron chelator deferoxamine, but exacerbated by supplement of ferric ammonium citrate...
April 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29697409/beginnings-of-nephrolithiasis-insights-into-the-past-present-and-future-of-randall-s-plaque-formation-research
#11
Scott V Wiener, Sunita P Ho, Marshall L Stoller
PURPOSE OF REVIEW: Kidney stones form as a result of heterogeneous nucleation on a calcium phosphate lesion in the renal papilla known as Randall's plaque. Stone disease has plagued humans for millennia with relatively little progress made in the realm of prevention. An understanding of the historical aspects of research into Randall's plaque is necessary to interpret novel correlative imaging discoveries. Focus for the past several decades has been on the distal papillary tip, and the overlooked Anderson-Carr-Randall progression is revitalized with novel supporting evidence...
April 24, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29693305/genetic-deletion-of-xct-attenuates-peripheral-and-central-inflammation-and-mitigates-lps-induced-sickness-and-depressive-like-behavior-in-mice
#12
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
https://www.readbyqxmd.com/read/29686608/modulation-of-autophagy-by-a-small-molecule-inverse-agonist-of-err%C3%AE-is-neuroprotective
#13
S N Suresh, Aravinda K Chavalmane, Malini Pillai, Veena Ammanathan, D J Vidyadhara, Haorei Yarreiphang, Shashank Rai, Abhik Paul, James P Clement, Phalguni A Alladi, Ravi Manjithaya
Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, are lacking. Here, we report and describe the role of Estrogen Related Receptor α (ERRα, HUGO Gene Nomenclature ESRRA), new molecular player of aggrephagy, in keeping autophagy flux in check by inhibiting autophagosome formation. A screen for small molecule modulators for aggrephagy identified ERRα inverse agonist XCT 790, that cleared α-synuclein aggregates in an autophagy dependent, but mammalian target of rapamycin (MTOR) independent manner...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29649284/sulfasalazine-an-inhibitor-of-the-cystine-glutamate-antiporter-reduces-dna-damage-repair-and-enhances-radiosensitivity-in-murine-b16f10-melanoma
#14
Masaki Nagane, Eiichi Kanai, Yuki Shibata, Takuto Shimizu, Chie Yoshioka, Takuya Maruo, Tadashi Yamashita
The sodium-independent cystine-glutamate antiporter plays an important role in extracellular cystine uptake. It comprises the transmembrane protein, xCT and its chaperone, CD98. Because glutathione is only weakly cell membrane permeable, cellular uptake of its precursor, cystine, is known to be a key step in glutathione synthesis. Moreover, it has been reported that xCT expression affects the progression of tumors and their resistance to therapy. Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential...
2018: PloS One
https://www.readbyqxmd.com/read/29604365/effects-of-ceftriaxone-on-hydrocodone-seeking-behavior-and-glial-glutamate-transporters-in-p-rats
#15
Fahad S Alshehri, Alqassem Y Hakami, Yusuf S Althobaiti, Youssef Sari
Hydrocodone (HYD) is one of the most widely prescribed opioid analgesic drugs. Several neurotransmitters are involved in opioids relapse. Among these neurotransmitters, glutamate is suggested to be involved in opioid dependence and relapse. Glutamate is regulated by several glutamate transporters, including glutamate transporter 1 (GLT-1) and cystine/glutamate transporter (xCT). In this study, we investigated the effects of ceftriaxone (CEF) (200 mg/kg, i.p.), known to upregulate GLT-1 and xCT, on reinstatement to HYD (5 mg/kg, i...
March 28, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29579243/aortic-cross-clamp-time-and-cardiopulmonary-bypass-time-prognostic-implications-in-patients-operated-on-for-infective-endocarditis
#16
Antonio Salsano, Daniele Roberto Giacobbe, Elena Sportelli, Guido Maria Olivieri, Roberto Natali, Martina Prevosto, Valerio Del Bono, Claudio Viscoli, Francesco Santini
OBJECTIVES: Prolonged aortic cross-clamp (XCT) and cardiopulmonary bypass time (CPBT) are associated with increased morbidity and mortality following cardiac surgery. The aim of this study was to assess the predictors of mortality and other severe postoperative complications in patients undergoing surgery for infective endocarditis (IE), focusing in particular on the role of prolonged XCT and CPBT. METHODS: A retrospective single-centre study was conducted from January 2000 to January 2017, including all patients undergoing valvular surgery for IE...
March 22, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29562573/markov-random-field-segmentation-for-industrial-computed-tomography-with-metal-artefacts
#17
Avinash Jaiswal, Mark A Williams, Abhir Bhalerao, Manoj K Tiwari, Jason M Warnett
X-ray Computed Tomography (XCT) has become an important tool for industrial measurement and quality control through its ability to measure internal structures and volumetric defects. Segmentation of constituent materials in the volume acquired through XCT is one of the most critical factors that influence its robustness and repeatability. Highly attenuating materials such as steel can introduce artefacts in CT images that adversely affect the segmentation process, and results in large errors during quantification...
March 15, 2018: Journal of X-ray Science and Technology
https://www.readbyqxmd.com/read/29545177/estrogen-related-receptor-%C3%AE-is-essential-for-maintaining-mitochondrial-integrity-in-cisplatin-induced-acute-kidney-injury
#18
Keigo Tsushida, Katsuyuki Tanabe, Kana Masuda, Satoshi Tanimura, Hiromasa Miyake, Yuka Arata, Hitoshi Sugiyama, Jun Wada
Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin...
April 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29517978/trap-seq-identifies-cystine-glutamate-antiporteras-a-driver-of-recovery-from-liver-injury
#19
Amber W Wang, Kirk J Wangensteen, Yue J Wang, Adam M Zahm, Nicholas G Moss, Noam Erez, Klaus H Kaestner
Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29488137/alterations-in-system-x-c-expression-in-the-retina-of-type-1-diabetic-rats-and-the-role-of-nrf2
#20
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
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