keyword
https://read.qxmd.com/read/37755645/identification-of-non-excitatory-amino-acids-and-transporters-mediating-the-irreversible-synaptic-silencing-after-hypoxia
#21
JOURNAL ARTICLE
Iris Álvarez-Merz, María-Dolores Muñoz, Jesús M Hernández-Guijo, José M Solís
The contribution of excitatory amino acids (AA) to ischemic brain injury has been widely described. In addition, we reported that a mixture of non-excitatory AA at plasmatic concentrations turns irreversible the depression of synaptic transmission caused by hypoxia. Here, we describe that the presence of seven non-excitatory AA (L-alanine, L-glutamine, glycine, L-histidine, L-serine, taurine, and L-threonine) during hypoxia provokes an irreversible neuronal membrane depolarization, after an initial phase of hyperpolarization...
September 27, 2023: Translational Stroke Research
https://read.qxmd.com/read/37658192/rna-binding-motif-protein-45-mediated-phosphorylation-enhances-protein-stability-of-asct2-to-promote-hepatocellular-carcinoma-progression
#22
JOURNAL ARTICLE
Danyu Du, Mengyao Qin, Li Shi, Chan Liu, Jingwei Jiang, Zhengguang Liao, Hongxv Wang, Zhibo Zhang, Li Sun, Hui Fan, Zhengrui Liu, Hong Yu, Hongyang Li, Jun Peng, Shengtao Yuan, Mei Yang, Jing Xiong
Targeting metabolic remodeling represents a potentially promising strategy for hepatocellular carcinoma (HCC) therapy. In-depth understanding on the regulation of the glutamine transporter alanine-serine-cysteine transporter 2 (ASCT2) contributes to the development of novel promising therapeutics. As a developmentally regulated RNA binding protein, RBM45 is capable to shuttle between nucleus and cytoplasm, and directly interacts with proteins. By bioinformatics analysis, we screened out that RBM45 was elevated in the HCC patient specimens and positively correlated with poor prognosis...
September 1, 2023: Oncogene
https://read.qxmd.com/read/37655270/lobetyolin-inhibits-cell-proliferation-and-induces-cell-apoptosis-by-downregulating-asct2-in-gastric-cancer
#23
JOURNAL ARTICLE
Lin Cheng, Haoqing Zhai, Juan Du, Gang Zhang, Gan Shi
Gastric cancer (GC) is a heterogeneous disease and is the fifth most common cancer worldwide. Lobetyolin, as a bioactive ingredient extracted from Codonopsis pilosula (Franch.) Nannf. , has been reported to exert anti-tumor effects in several cancer types. This study was aimed to investigate the role of lobetyolin in GC and the associated mechanism. MKN-45 and MKN-28 cells were incubated with concentrations of lobetyolin for 24 h. The viability and survival of GC cells were evaluated by performing MTT assay...
October 2023: Cytotechnology
https://read.qxmd.com/read/37634599/asct2-mediated-glutamine-uptake-promotes-th1-differentiation-via-ros-egr1-pac1-pathway-in-oral-lichen-planus
#24
JOURNAL ARTICLE
Wei Li, Zihang Ling, Jinmei Wang, Zhangci Su, Jingyi Lu, Xi Yang, Bin Cheng, Xiaoan Tao
Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa concerning with the redox imbalance. Although glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) is critical to T cell differentiation, the exact mechanism remains ambiguous. Here, we elucidate a novel regulatory mechanism of ASCT2-mediated uptake in the differentiation and proliferation of T cells through maintaining redox balance in OLP. The results of immunohistochemistry (IHC) showed that both ASCT2 and glutaminase (GLS) were obviously upregulated compared to controls in OLP...
August 25, 2023: Biochemical Pharmacology
https://read.qxmd.com/read/37578594/loss-of-rack1-promotes-glutamine-addiction-via-activating-akt-mtor-asct2-axis-to-facilitate-tumor-growth-in-gastric-cancer
#25
JOURNAL ARTICLE
Mengqian Chen, Gaojia Wang, Zhijian Xu, Jie Sun, Bo Liu, Lei Chang, Jianxin Gu, Yuanyuan Ruan, Xiaodong Gao, Shushu Song
BACKGROUND: Metabolic reprogramming is closely related to the development of gastric cancer (GC), which remains as the fourth leading cause of cancer-related death worldwide. As a tumor suppressor for GC, whether receptor for activated C-kinase 1 (RACK1) play a modulatory role in metabolic reprogramming remains largely unclear. METHODS: GC cell lines and cell-derived xenograft mouse model were used to identify the biological function of RACK1. Flow cytometry and Seahorse assays were applied to examine cell cycle and oxygen consumption rate (OCR), respectively...
August 14, 2023: Cellular Oncology (Dordrecht)
https://read.qxmd.com/read/37577547/a-cell-autonomous-mechanism-regulates-bcaa-catabolism-in-white-adipocytes-and-systemic-metabolic-balance
#26
Ashley M Aguillard, Joyce Tzeng, Ismael Ferrer, Bjorn T Tam, Damaris N Lorenzo
UNLABELLED: Elevated plasma branched-chain amino acids (BCAAs) are strongly associated with obesity, insulin resistance (IR), and diabetes in humans and rodent models. However, the mechanisms of BCAA dysregulation and its systemic, organ, and cell-specific implications in the development of obesity and IR are not well understood. To gain mechanistic insight into the causes and effects of plasma BCAA elevations, we leveraged mouse models with high circulating BCAA levels prior to the onset of obesity and IR...
August 1, 2023: bioRxiv
https://read.qxmd.com/read/37553484/therapeutic-applications-of-local-injection-of-hsa-mir-634-into-canine-spontaneous-malignant-melanoma-tumors
#27
JOURNAL ARTICLE
Ryutaro Yoshikawa, Jun Inoue, Ryota Iwasaki, Mitsuhiko Terauchi, Yuji Fujii, Maya Ohta, Tomomi Hasegawa, Rui Mizuno, Takashi Mori, Johji Inazawa
Malignant melanoma (MM) is one of the most common tumors in both dogs and humans. As canine MM (CMM) and human MM (HMM) have similar clinical characteristics, CMM appears to be a good clinical model for HMM. We previously demonstrated that the introduction of a synthetic double-strand-microRNA-634 (miR-634) mimic triggered apoptotic cell death by directly targeting the genes associated with cytoprotective processes in various human cancer cell lines, including those of HMM. This study aimed to investigate the antitumor effects of the local administration of miR-634 on spontaneous CMMs to provide a basis for future applications of miR-634 formulations in HMM treatment...
August 8, 2023: Cancer Gene Therapy
https://read.qxmd.com/read/37481142/methylseleninic-acid-overcomes-gefitinib-resistance-through-asparagine-met-topk-signaling-axis-in-non-small-cell-lung-cancer-cells
#28
JOURNAL ARTICLE
Jinling Cui, Shuang Zhao, Hui Chen, Yuhan Fu, Kai Han, Shutao Yin, Chong Zhao, Lihong Fan, Hongbo Hu
Acquired resistance compromises the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-based therapy for non-small cell lung cancer (NSCLC), and activation of hepatocyte growth factor receptor (MET) is one of the pivotal strategies for cancer cells to acquire refractory phenotype. However, the mechanisms involved in regulating MET activity remain to be further elucidated. Using gefitinib-resistant HCC827GR cell line as a model, we unraveled that the dysregulated amino acid metabolisms reflected by elevated expression of cysteine-preferring transporter 2 (ASCT2), cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) and asparagine synthetase (ASNS) might contribute to survival advantage of HCC827GR cells, and rendered the cells more sensitive to asparagine (ASN) deprivation compared to parental HCC827 cells...
July 20, 2023: Biochemical Pharmacology
https://read.qxmd.com/read/37478011/quas-r-an-slc1a5-mediated-glutamine-uptake-assay-with-single-cell-resolution-reveals-metabolic-heterogeneity-with-immune-populations
#29
JOURNAL ARTICLE
Leonard R Pelgrom, Gavin M Davis, Simon O'Shaughnessy, Emilie J M Wezenberg, Sander I Van Kasteren, David K Finlay, Linda V Sinclair
System-level analysis of single-cell data is rapidly transforming the field of immunometabolism. Given the competitive demand for nutrients in immune microenvironments, there is a need to understand how and when immune cells access these nutrients. Here, we describe a new approach for single-cell analysis of nutrient uptake where we use in-cell biorthogonal labeling of a functionalized amino acid after transport into the cell. In this manner, the bona fide active uptake of glutamine via SLC1A5/ASCT2 could be quantified...
July 19, 2023: Cell Reports
https://read.qxmd.com/read/37473513/preclinical-radiolabeling-in-vivo-biodistribution-and-positron-emission-tomography-of-a-novel-pyrrolobenzodiazepine-pbd-based-antibody-drug-conjugate-targeting-asct2
#30
JOURNAL ARTICLE
Christian Werner Wichmann, Ingrid Julienne Georgette Burvenich, Nancy Guo, Angela Rigopoulos, Alexander McDonald, Diana Cao, Graeme Joseph O'Keefe, Sylvia Jie Gong, Hui Kong Gan, Fiona Elizabeth Scott, Nabendu Pore, Steven Coats, Andrew Mark Scott
INTRODUCTION: Anti-ASCT2 antibody drug conjugate (ADC) MEDI7247 has been under development as a potential anti-cancer therapy for patients with selected relapsed/refractory hematological malignancies and advanced solid tumors by MedImmune. Although promising efficacy was observed in the clinic, pharmacokinetic (PK) analyses observed low exposure of MEDI7247 in phase I hematological patients. To investigate the biodistribution properties of MEDI7247, MEDI7247 and control antibodies were radiolabeled with zirconium-89 and in vitro and in vivo properties characterized...
July 14, 2023: Nuclear Medicine and Biology
https://read.qxmd.com/read/37420266/cafs-targeted-ultrasound-responsive-nanodroplets-loaded-v9302-and-glulsirna-to-inhibit-melanoma-growth-via-glutamine-metabolic-reprogramming-and-tumor-microenvironment-remodeling
#31
JOURNAL ARTICLE
Chen Ai, Xiao Sun, Shan Xiao, Lu Guo, Mengmeng Shang, Dandan Shi, Dong Meng, Yading Zhao, Xiaoxuan Wang, Jie Li
Despite rapid advances in metabolic therapies over the past decade, their efficacy in melanoma has been modest, largely due to the interaction between cancer-associated fibroblasts (CAFs) and cancer cells to promote cancer growth. Altering the tumor microenvironment (TME) is challenging and elusive. CAFs is critical for glutamine deprivation survival in melanoma. In this research, we assembled a CAFs-targeted, controlled-release nanodroplets for the combined delivery of the amino acid transporter ASCT2 (SLC1A5) inhibitor V9302 and GLULsiRNA (siGLUL)...
July 8, 2023: Journal of Nanobiotechnology
https://read.qxmd.com/read/37410896/lipopolysaccharide-promotes-apoptosis-and-oxidative-injury-of-porcine-small-intestinal-epithelial-cells-by-down-regulating-the-expression-of-glutamine-transporter-asct2
#32
JOURNAL ARTICLE
Xiaopeng Tang, Kangning Xiong, Jia Liu, Meijun Li
The present study aimed to investigate the effects of lipopolysaccharide (LPS) stimulation on oxidative damage, apoptosis, and glutamine (Gln) transporter Alanine-Serine-Cysteine transporter 2 (ASCT2) expression in porcine small intestinal epithelial cells (IPEC-J2), and preliminarily elucidated the relationship between ASCT2 expression level and oxidative damage and apoptosis of IPEC-J2 cells. IPEC-J2 cells were treated without (control group, CON, n=6) or with 1 μg/mL LPS (LPS group, LPS, n=6). Cell viability, lactate dehydrogenase (LDH) content, malonaldehyde (MDA), antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC)], apoptosis of IPEC-J2 cells, the expression of Caspase3, the expression of ASCT2 mRNA and ASCT2 protein was detected...
July 6, 2023: Journal of Animal Science
https://read.qxmd.com/read/37408893/a-pan-cancer-analysis-of-slc1a5-in-human-cancers
#33
JOURNAL ARTICLE
Juan Ni, Wumin Dai, Chun Liu, Yutian Ling, Hanzhou Mou
BACKGROUND: The alanine-serine-cysteine transporter 2, ASCT2 (solute carrier family 1 member 5, SLC1A5), is a major transporter of the amino acid, glutamine. Although SLC1A5 has been reported to be associated with some types of cancer, less pan-cancer analysis, which would give a comprehensive understanding of SLC1A5 across human cancers, has been carried out. METHODS: We used the TCGA and GEO databases to investigate the oncogenic role of SLC1A5. We examined gene and protein expression, survival, genetic mutations, protein phosphorylation, immunocyte infiltration and the related genes correlated pathways...
June 2023: Heliyon
https://read.qxmd.com/read/37401237/regulation-of-glucose-and-glutamine-metabolism-to-overcome-cisplatin-resistance-in-intrahepatic-cholangiocarcinoma
#34
So Mi Yang, Jueun Kim, Ji-Yeon Lee, Jung-Shin Lee, Ji Min Lee
Intrahepatic cholangiocarcinoma (ICC) is one of the bile duct cancers and a rare malignant tumor with a poor prognosis owing to a lack of early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is a treatment approach typically being attempted for the first line. However, its underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying the dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism is a key factor in overcoming cisplatin resistance of SCK...
July 4, 2023: BMB Reports
https://read.qxmd.com/read/37393816/slc1a5-regulates-cell-proliferation-and-self-renewal-through-%C3%AE-catenin-pathway-mediated-by-redox-signaling-in-arsenic-treated-uroepithelial-cells
#35
JOURNAL ARTICLE
Sihao Li, Liang Pei, Qing Zhou, Zhushan Fu, Lei Zhang, Pinya Liu, Nan Yan, Shuhua Xi
Arsenic exposure increases the risk of bladder cancer in humans, but its underlying mechanisms remain elusive. The alanine, serine, cysteine-preferring transporter 2 (ASCT2, SLC1A5) is frequently overexpressed in cancer cells. The aim of this study was to evaluate the effects of arsenic on SLC1A5, and to determine the role of SLC1A5 in the proliferation and self-renewal of uroepithelial cells. F344 rats were exposed to 87 mg/L NaAsO2 or 200 mg/L DMAV for 12 weeks. The SV-40 immortalized human uroepithelial (SV-HUC-1) cells were cultured in medium containing 0...
June 30, 2023: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/37353852/development-of-a-method-for-isolating-brain-capillaries-from-a-single-neonatal-mouse-brain-and-comparison-of-proteomic-profiles-between-neonatal-and-adult-brain-capillaries
#36
JOURNAL ARTICLE
Yudai Hamada, Seiryo Ogata, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki
BACKGROUND: The functions and protein expressions of the blood-brain barrier are changed throughout brain development following birth. This study aimed to develop a method to isolate brain capillaries from a single frozen neonatal mouse brain and elucidate the enrichment of brain capillaries by quantitative proteomic analysis. We further compared the expression profile of proteins between neonatal and adult brain capillary fractions. METHODS: The brain capillary fraction was prepared by the optimized method from a single frozen mouse neonatal brain on postnatal day 7...
June 23, 2023: Fluids and Barriers of the CNS
https://read.qxmd.com/read/37249811/glycyrrhinic-acid-and-probiotics-alleviate-deoxynivalenol-induced-cytotoxicity-in-intestinal-epithelial-cells
#37
JOURNAL ARTICLE
Xiaoxiang Xu, Juan Chang, Ping Wang, Chaoqi Liu, Ting Zhou, Qingqiang Yin, Guorong Yan
Deoxynivalenol (DON) is one of the most prevalent mycotoxin contaminants, which posing a serious health threat to animals and humans. Previous studies have found that individually supplemented probiotic or glycyrrhinic acid (GA) could degrade DON and alleviate DON-induced cytotoxicity. The present study investigated the effect of combining GA with Saccharomyces cerevisiae (S. cerevisiae) and Enterococcus faecalis (E. faecalis) using orthogonal design on alleviating IPEC-J2 cell damage induced by DON. The results showed that the optimal counts of S...
May 30, 2023: AMB Express
https://read.qxmd.com/read/37207473/lncrna-sytl5-ot4-promotes-vessel-co-option-by-inhibiting-the-autophagic-degradation-of-asct2
#38
JOURNAL ARTICLE
Qing Wen, Maohua Huang, Jingwen Xie, Runyu Liu, Qun Miao, Jinjun Huang, Junqiu Zhang, Wenyu Lyu, Ming Qi, Chunyi Wu, Qi Qi, Zhijing Zhang, Rong Deng, Chenran Wang, Zhe-Sheng Chen, Dongmei Zhang, Wencai Ye, Minfeng Chen
AIMS: Vessel co-option is responsible for tumor resistance to antiangiogenic therapies (AATs) in patients with colorectal cancer liver metastasis (CRCLM). However, the mechanisms underlying vessel co-option remain largely unknown. Herein, we investigated the roles of a novel lncRNA SYTL5-OT4 and Alanine-Serine-Cysteine Transporter 2 (ASCT2) in vessel co-option-mediated AAT resistance. METHODS: SYTL5-OT4 was identified by RNA-sequencing and verified by RT-qPCR and RNA fluorescence in situ hybridization assays...
July 2023: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/37116342/asct2-mediated-glutamine-uptake-of-epithelial-cells-facilitates-ccl5-induced-t-cell-infiltration-via-ros-stat3-pathway-in-oral-lichen-planus
#39
JOURNAL ARTICLE
Jingyi Lu, Zhangci Su, Wei Li, Zihang Ling, Bin Cheng, Xi Yang, Xiaoan Tao
BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease characterized by T cell infiltration at lesion sites. T cell migration is greatly facilitated by chemokines produced by epithelial cells. Studies have noted the potential role of glutamine uptake in OLP and other inflammatory diseases. Here, we investigated the effect of altered glutamine uptake of epithelial cells on T cell infiltration and its underlying mechanisms in OLP. METHODS: Immunohistochemistry was used to identify the expressions of glutamine transporter alanine-serine-cysteine transporter 2 (ASCT2) and C-C motif chemokine ligand 5 (CCL5) in oral tissues of OLP and healthy controls...
April 26, 2023: International Immunopharmacology
https://read.qxmd.com/read/37115356/in-vitro-evaluation-of-s-2-amino-3-3-2-18-f-fluoroethoxy-4-iodophenyl-2-methylpropanoic-acid-18-f-fimp-as-a-positron-emission-tomography-probe-for-imaging-amino-acid-transporters
#40
JOURNAL ARTICLE
Satoshi Nozaki, Yuka Nakatani, Aya Mawatari, William Ewan Hume, Hisashi Doi, Yasuyoshi Watanabe
BACKGROUND: (S)-2-amino-3-[3-(2-18 F-fluoroethoxy)-4-iodophenyl]-2-methylpropanoic acid (18 F-FIMP) as a promising PET probe for imaging the tumor-specific L-type amino acid transporter (LAT) 1. Our previous study revealed that 18 F-FIMP had a higher affinity for LAT1 than for LAT2 abundantly expressed even in normal cells. 18 F-FIMP showed high accumulation in LAT1-positive tumor tissues and low accumulation in inflamed lesions in tumor-bearing mice. However, the affinity of 18 F-FIMP for other amino acid transporters was not determined yet...
April 28, 2023: EJNMMI Research
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