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https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#1
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28712392/-protection-of-rho-associated-protein-kinase-inhibitor-y-27632-in-mrl-lpr-mice
#2
Yuanyuan Wang, Xiaoyun Jia, Qiyi Wang, Ming Ye, Yang Lu, Jiajia Zhang, Sheng Chen, Yanglei Li, Junying Wu, Changhao Xie
Objective To investigate the immunological effect of Rho-associated protein kinase inhibitor Y-27632 on MRL/lpr mice and explore its underlying mechanisms. Methods The study collected 10 wild-type C57BL/6 mice as normal controls and 20 MRL/lpr mice that were randomly assigned to MRL/lpr group and 5 mg/kg Y-27632-treated MRL/lpr group, with 10 mice in each group. Superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), interleukin 6 (IL-6), IL-1β and tumor necrosis factor α (TNF-α) in the serum or spleen were detected by ELISA...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28700004/dexmedetomidine-protects-against-renal-ischemia-and-reperfusion-injury-by-inhibiting-the-p38-mapk-txnip-signaling-activation-in-streptozotocin-induced-diabetic-rats
#3
Xiao Yeda, Lei Shaoqing, Huang Yayi, Zhao Bo, Wang Huaxin, Cao Hong, Xia Zhongyuan
Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion...
June 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28694028/the-pivotal-role-of-extracellular-signal-regulated-kinase-in-gap-junction-mediated-regulation-of-txnip
#4
Shan Gao, Xiling Zhang, Kun Gao, Zhen Zhang, Yanru Huang, Ryuichi Yoda, Jian Yao
Gap junctions (GJs) play a major role in the control of cell structure, function, and metabolism. However, the molecular mechanisms involved are still poorly understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad range of cellular processes, we tested the possible involvement of TXNIP. Disruption of GJs with several chemical GJ inhibitors or connexin43 (Cx43) siRNA potently suppressed TXNIP, which was preceded by an activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK or its upstream kinase with chemical inhibitors prevented the reduction of TXNIP...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28669627/endogenous-hydrogen-sulfide-mediated-mapk-inhibition-preserves-endothelial-function-through-txnip-signaling
#5
Danyang Tian, Jinghui Dong, Sheng Jin, Xu Teng, Yuming Wu
Mounting evidence demonstrated deficient cystathionine-γ-lyase (CSE)/H2S implicated the development of cardiovascular disease. The present study aimed to evaluating the favorable action of CSE derived H2S on endothelial function in CSE(-/-) mice. CSE(-/-) mice exhibited attenuated endothelium-dependent relaxations, coupled with reduction of endothelial nitric oxide synthase (eNOS) phosphorylation at site of Ser1177, increase of thioredoxin interacting protein (TXNIP) level and MAPK phosphorylation, which were corrected by sodium hydrosulfide chronic treatment for 8 weeks...
June 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28661427/deletion-of-txnip-mitigates-high-fat-diet-impaired-angiogenesis-and-prevents-inflammation-in-a-mouse-model-of-critical-limb-ischemia
#6
Sally L Elshaer, Islam N Mohamed, Maha Coucha, Sara Altantawi, Wael Eldahshan, Megan L Bartasi, Ahmed Y Shanab, Renee Lorys, Azza B El-Remessy
BACKGROUND: Previous work demonstrated that high-fat diet (HFD) triggered thioredoxin-interacting protein (TXNIP) and that silencing TXNIP prevents diabetes-impaired vascular recovery. Here, we examine the impact of genetic deletion of TXNIP on HFD-impaired vascular recovery using hind limb ischemia model. METHODS: Wild type mice (WT, C57Bl/6) and TXNIP knockout mice (TKO) were fed either normal chow diet (WT-ND and TKO-ND) or 60% high-fat diet (WT-HFD and TKO-HFD)...
June 29, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28651973/1-25-oh-2d3-disrupts-glucose-metabolism-in-prostate-cancer-cells-leading-to-a-truncation-of-the-tca-cycle-and-inhibition-of-txnip-expression
#7
Mohamed A Abu El Maaty, Hamed Alborzinia, Shehryar J Khan, Michael Büttner, Stefan Wölfl
Prostate cell metabolism exhibits distinct profiles pre- and post-malignancy. The malignant metabolic shift converts prostate cells from "citrate-producing" to "citrate-oxidizing" cells, thereby enhancing glucose metabolism, a phenotype that contrasts classical tumoral Warburg metabolism. An on-line biosensor chip system (BIONAS 2500) was used to monitor metabolic changes (glycolysis and respiration) in response to the putative anti-cancer nutraceutical 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in different prostate cancer (PCa) cell lines (LNCaP, VCaP, DU145 and PC3)...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#8
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28606928/mtor-controls-chrebp-transcriptional-activity-and-pancreatic-%C3%AE-cell-survival-under-diabetic-stress
#9
Gia Cac Chau, Dong Uk Im, Tong Mook Kang, Jeong Mo Bae, Won Kim, Suhkneung Pyo, Eun-Yi Moon, Sung Hee Um
Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and β cell survival under diabetic stress is not well understood. Here, we show that mice lacking the core nutrient-sensitive signaling component mammalian target of rapamycin (mTOR) in β cells exhibit reduced β cell mass and smaller islets. mTOR deficiency leads to a severe reduction in β cell survival and increased mitochondrial oxidative stress in chemical-induced diabetes...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28606927/mtorc-in-%C3%AE-cells-more-than-only-recognizing-comestibles
#10
Kathrin Maedler, Amin Ardestani
The pathways regulating pancreatic β cell survival in diabetes are poorly understood. Here, Chau et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701085) demonstrate that mTOR regulates the apoptotic machinery through binding to the ChREBP-Mlx complex to suppress TXNIP, thereby protecting pancreatic β cells in the diabetic setting by inhibiting oxidative stress and mitochondrial dysfunction.
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28605158/the-effect-of-liraglutide-on-dietary-lipid-induced-insulin-resistance-in-humans
#11
Juraj Koska, Lizette Lopez, Karen D'Souza, Tracy Osredkar, James Deer, Julie Kurtz, Arline D Salbe, S Mitchell Harman, Peter D Reaven
AIMS: High saturated fatty acid (SFA) diets blunt peripheral insulin action. GLP-1 receptor agonists suppress postprandial lipids and endothelial dysfunction, which may counter SFA-induced insulin resistance. This study tested whether liraglutide suppresses postprandial elevations in lipids and thus protects against high SFA-diet induced insulin resistance. MATERIALS AND METHODS: In a randomized placebo-controlled cross-over study, 32 subjects with normal or mildly impaired glucose tolerance received liraglutide and placebo for 3 weeks each...
June 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28591573/phosphorylation-of-txnip-by-akt-mediates-acute-influx-of-glucose-in-response-to-insulin
#12
Althea N Waldhart, Holly Dykstra, Anderson S Peck, Elissa A Boguslawski, Zachary B Madaj, Jennifer Wen, Kelsey Veldkamp, Matthew Hollowell, Bin Zheng, Lewis C Cantley, Timothy E McGraw, Ning Wu
Growth factors, such as insulin, can induce both acute and long-term glucose uptake into cells. Apart from the rapid, insulin-induced fusion of glucose transporter (GLUT)4 storage vesicles with the cell surface that occurs in muscle and adipose tissues, the mechanism behind acute induction has been unclear in other systems. Thioredoxin interacting protein (TXNIP) has been shown to be a negative regulator of cellular glucose uptake. TXNIP is transcriptionally induced by glucose and reduces glucose influx by promoting GLUT1 endocytosis...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28502980/w2476-ameliorates-%C3%AE-cell-dysfunction-and-exerts-therapeutic-effects-in-mouse-models-of-diabetes-via-modulation-of-the-thioredoxin-interacting-protein-signaling-pathway
#13
Ting Li, Guang-Yao Lin, Li Zhong, Yan Zhou, Jia Wang, Yue Zhu, Yang Feng, Xiao-Qing Cai, Qing Liu, Olivier Nosjean, Jean A Boutin, Pierre Renard, De-Hua Yang, Ming-Wei Wang
Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in β-cells. Overexpression of txnip not only induces β-cell apoptosis but also reduces insulin production. Thus, the discovery of compounds that either inhibit TXNIP activity or suppress its expression was the focus of the present study. INS-1E cells stably transfected with either a txnip proximal glucose response element connected to a luciferase reporter plasmid (BG73) or full-length txnip promoter connected to a luciferase reporter plasmid (CL108) were used in primary and secondary high-throughput screening campaigns, respectively...
July 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28499273/inhibition-of-nlrp3-inflammasome-by-thioredoxin-interacting-protein-in-mouse-kupffer-cells-as-a-regulatory-mechanism-for-non-alcoholic-fatty-liver-disease-development
#14
Kun He, Xiwen Zhu, Yan Liu, Chunmu Miao, Tao Wang, Peizhi Li, Lei Zhao, Yaxi Chen, Junhua Gong, Can Cai, Jinzheng Li, Shengwei Li, Xiong Z Ruan, Jianping Gong
NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/- (thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499186/effect-of-betaine-on-hepatic-insulin-resistance-through-foxo1-induced-nlrp3-inflammasome
#15
Dae Hyun Kim, Seong Min Kim, Bonggi Lee, Eun Kyeong Lee, Ki Wung Chung, Kyoung Mi Moon, Hye Jin An, Kyung Mok Kim, Byung Pal Yu, Hae Young Chung
In the present study, we attempted to elucidate whether molecular modulation of inflammation by betaine through the forkhead box O1 (FOXO1)-induced NLRP3 inflammasome improves insulin resistance. Betaine is a major water-soluble component of Lycium chinense. It mainly functions as an oxidative metabolite of choline by suppressing superoxide-induced free radicals by donating methyl groups. The FOXO1 transcription factor regulates various genes involved in cellular metabolic processes related to cell death as well as oxidative stress responses through binding to the thioredoxin-interacting protein (TXNIP)...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28492550/txnip-regulates-mitophagy-in-retinal-m%C3%A3-ller-cells-under-high-glucose-conditions-implications-for-diabetic-retinopathy
#16
Takhellambam Swornalata Devi, Mallika Somayajulu, Renu Anjan Kowluru, Lalit Pukhrambam Singh
Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains unexplored. Here we investigate the associated cellular and molecular mechanisms underlying mitophagy in retinal cells under diabetic conditions. For this, we maintained a rat Müller cell line (rMC1) under high-glucose (25 mM, HG) or low-glucose (5.5 mM, LG) condition for 5 days...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28490373/thioredoxin-interacting-protein-links-endoplasmic-reticulum-stress-to-inflammatory-brain-injury-and-apoptosis-after-subarachnoid-haemorrhage
#17
Qing Zhao, Xudong Che, Hongxia Zhang, Pianpian Fan, Guanping Tan, Liu Liu, Dengzhi Jiang, Jun Zhao, Xiang Xiang, Yidan Liang, Xiaochuan Sun, Zhaohui He
BACKGROUND: Early brain injury (EBI) is considered a major contributor to the high morbidity and mortality associated with subarachnoid haemorrhage (SAH). Both of sterile inflammation and apoptosis are considered the important causes of EBI. Recently, it was confirmed that thioredoxin-interacting protein (TXNIP) not only participates in inflammatory amplification but also stimulates the apoptosis signalling cascade pathway. However, whether the effects of TXNIP influence the pathogenesis of SAH remains unclear...
May 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28483515/thioredoxin-1-promotes-colorectal-cancer-invasion-and-metastasis-through-crosstalk-with-s100p
#18
Feiyan Lin, Peili Zhang, Zhigui Zuo, Fule Wang, Ruichun Bi, Wenjing Shang, Aihua Wu, Ju Ye, Shaotang Li, Xuecheng Sun, Jianbo Wu, Lei Jiang
Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival...
May 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28440491/txnip-overexpression-suppresses-proliferation-and-induces-apoptosis-in-smmc7221-cells-through-ros-generation-and-mapk-pathway-activation
#19
Jian Li, Zhongyi Yue, Wancheng Xiong, Peisheng Sun, Kun You, Jianguo Wang
Thioredoxin binding protein (thioredoxin-interacting protein, TXNIP), known as vitamin D3 increase protein 1, has been identified as a tumor suppressor in various cancers such as pancreatic, breast, lung and thyroid cancer. However, the role of TXNIP in hepatocellular carcinoma cell proliferation and apoptosis remains unknown. In this study, we first used qRT-PCR, western blotting and immunohistochemistry to compare the expression of TXNIP between hepatocellular carcinoma tissues and tumor-adjacent normal liver tissues...
April 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28420192/thioredoxin-interacting-protein-mediates-apoptosis-in-early-brain-injury-after-subarachnoid-haemorrhage
#20
Qing Zhao, Xudong Che, Hongxia Zhang, Guanping Tan, Liu Liu, Dengzhi Jiang, Jun Zhao, Xiang Xiang, Xiaochuan Sun, Zhaohui He
Early brain injury (EBI) is considered to be the major factor associated with high morbidity and mortality after subarachnoid haemorrhage (SAH). Apoptosis is the major pathological mechanism of EBI, and its pathogenesis has not been fully clarified. Here, we report that thioredoxin-interacting protein (TXNIP), which is induced by protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK), participates in EBI by promoting apoptosis. By using adult male Sprague-Dawley rats to establish SAH models, as well as Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining, immunofluorescence, and western blot, we found that TXNIP expression significantly increased after SAH in comparison to the sham group and peaked at 48 h (up to 3...
April 18, 2017: International Journal of Molecular Sciences
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