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https://www.readbyqxmd.com/read/27936392/rutin-protects-endothelial-dysfunction-by-disturbing-nox4-and-ros-sensitive-nlrp3-inflammasome
#1
Wei Wang, Qiu-Hong Wu, Yong Sui, Yan Wang, Xin Qiu
High glucose induced endothelial dysfunction is blamed for initiation of vascular complication in Type 2 diabetes mellitus. Rutin has been described in possessing comprehensive pharmacological activities, but the mechanism involved in endothelial protection through regulating oxidative stress and damage is still ambiguous. In the present study, rutin was evaluated in high glucose stimulated human umbilical vein endothelial cells (HUVECs) and high glucose diet-treated SD rats were applied to explored the molecular mechanism in rutin counteracting oxidative stress and damage...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27929088/thioredoxin-interacting-protein-regulates-haematopoietic-stem-cell-ageing-and-rejuvenation-by-inhibiting-p38-kinase-activity
#2
Haiyoung Jung, Dong Oh Kim, Jae-Eun Byun, Won Sam Kim, Mi Jeong Kim, Hae Young Song, Young Kwan Kim, Du-Kyeong Kang, Young-Jun Park, Tae-Don Kim, Suk Ran Yoon, Hee Gu Lee, Eun-Ji Choi, Sang-Hyun Min, Inpyo Choi
Ageing is a natural process in living organisms throughout their lifetime, and most elderly people suffer from ageing-associated diseases. One suggested way to tackle such diseases is to rejuvenate stem cells, which also undergo ageing. Here we report that the thioredoxin-interacting protein (TXNIP)-p38 mitogen-activated protein kinase (p38) axis regulates the ageing of haematopoietic stem cells (HSCs), by causing a higher frequency of long-term HSCs, lineage skewing, a decrease in engraftment, an increase in reactive oxygen species and loss of Cdc42 polarity...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27898405/n-acetyl-cysteine-attenuated-the-deleterious-effects-of-advanced-glycation-end-products-on-the-kidney-of-non-diabetic-rats
#3
Karina Thieme, Karolline S Da Silva, Nelly T Fabre, Sergio Catanozi, Maria Beatriz Monteiro, Daniele Pereira Santos-Bezerra, Juliana Martins Costa-Pessoa, Maria Oliveira-Souza, Ubiratan F Machado, Marisa Passarelli, Maria Lucia Correa-Giannella
AIM: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC). METHODS: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27867451/thioredoxin-interacting-protein-mediates-nlrp3-inflammasome-activation-involved-in-the-susceptibility-to-ischemic-acute-kidney-injury-in-diabetes
#4
Ye Da Xiao, Ya Yi Huang, Hua Xin Wang, Yang Wu, Yan Leng, Min Liu, Qian Sun, Zhong-Yuan Xia
Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI). However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP) expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R-) induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES) treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction)...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27833015/trimethylamine-n-oxide-induces-inflammation-and-endothelial-dysfunction-in-human-umbilical-vein-endothelial-cells-via-activating-ros-txnip-nlrp3-inflammasome
#5
Xiaolei Sun, Xuefei Jiao, Yarong Ma, Yong Liu, Lei Zhang, Yanzheng He, Yunhui Chen
Recent research demonstrates that the choline-derived metabolite trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis and cardiovascular risks. The NLRP3 inflammasome responds to exogenous and endogenous danger signals involved in the development of atherosclerosis. Moreover, thioredoxin-interactive protein (TXNIP) activation is a key event linked to NLRP3 inflammasome via reactive oxygen species (ROS). Whether TMAO prime NLRP3 inflammasome via ROS-TXNIP pathway remains unclear...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27832995/protective-effect-of-sophoraflavanone-g-on-streptozotocin-stz-induced-inflammation-in-diabetic-rats
#6
Hanqing Wang, Li Chen, Liming Zhang, Xiaojuan Gao, Yinghua Wang, Tao Weiwei
The present study was designed to investigate the protective effect of Sophoraflavanone G (SG) on streptozotocin (STZ)-induced diabetic rats. The rats were intraperitoneally injected with STZ (35mg/kg). 7days later, the rats were intragastrically administered with Metformin (MET, 150mg/kg), SG (20mg/kg) or SG (40mg/kg) once daily for consecutive 30 days. The animals were anaesthetized, the blood and liver samples were also collected for further assay. SG significantly decreased the serum levels of glucose, insulin, aspartate transaminase (AST), alanine aminotransferase (ALT)...
November 7, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27816762/long-term-administration-of-advanced-glycation-end-product-stimulates-the-activation-of-nlrp3-inflammasome-and-sparking-the-development-of-renal-injury
#7
Wan-Ju Yeh, Hsin-Yi Yang, Man-Hui Pai, Chi-Hao Wu, Jiun-Rong Chen
The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27807222/the-emerging-role-of-thioredoxin-interacting-protein-in-myocardial-ischemia-reperfusion-injury
#8
Bing F Wang, Jun Yoshioka
Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification of numerous molecular mechanisms, understanding of the complex pathophysiology of this clinical syndrome remains incomplete. Thioredoxin-interacting protein (Txnip) has been of great interest in the past decade since it has been reported to be a critical regulator in human diseases with several important cellular functions. Thioredoxin-interacting protein binds to and inhibits thioredoxin, a redox protein that neutralizes reactive oxygen species (ROS), and through its interaction with thioredoxin, Txnip sensitizes cardiomyocytes to ROS-induced apoptosis...
November 2, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27785530/activation-of-the-txnip-nlrp3-inflammasome-pathway-contributes-to-inflammation-in-diabetic-retinopathy-a-novel-inhibitory-effect-of-minocycline
#9
Wei Chen, Minjie Zhao, Shuzhi Zhao, Qianyi Lu, Lisha Ni, Chen Zou, Li Lu, Xun Xu, Huaijin Guan, Zhi Zheng, Qinghua Qiu
OBJECTIVE AND DESIGN: Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. METHODS: Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks...
October 26, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27762463/differential-expression-of-thioredoxin-binding-protein-2-txnip-in-human-placenta-possible-involvement-of-hypoxia-in-its-suppression-during-early-pregnancy
#10
Haruta Mogami, Shigeo Yura, Eiji Kondoh, Hiroshi Masutani, Junji Yodoi, Ikuo Konishi
AIM: Thioredoxin binding protein-2 (TBP-2), which is identical to thioredoxin interacting protein (Txnip), controls cellular proliferation and differentiation. The aim of the present study was to compare TBP-2 protein and mRNA expression in human placenta during the three trimesters of pregnancy and to investigate the role of hypoxia in the change of these expressions in placental tissue. A secondary objective was to determine the gene expression of peroxisome proliferator-activated receptors (PPARs) in TBP-2 deficient placenta using TBP-2 gene disrupted mice (TBP-2(-/-) )...
October 20, 2016: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/27753144/melatonin-rescues-cardiac-thioredoxin-system-during-ischemia-reperfusion-injury-in-acute-hyperglycemic-state-by-restoring-notch1-hes1-akt-signaling-in-a-membrane-receptor-dependent-manner
#11
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27746687/ginsenoside-rb1-and-compound-k-improve-insulin-signaling-and-inhibit-er-stress-associated-nlrp3-inflammasome-activation-in-adipose-tissue
#12
Weijie Chen, Junlian Wang, Yong Luo, Tao Wang, Xiaochun Li, Aiyun Li, Jia Li, Kang Liu, Baolin Liu
BACKGROUND: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. METHODS: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry...
October 2016: Journal of Ginseng Research
https://www.readbyqxmd.com/read/27733245/differential-inflammasome-activation-signatures-following-intracellular-infection-of-human-macrophages-with-mycobacterium-bovis-bcg-or-trypanosoma-cruzi
#13
M B Huante, S Gupta, V C Calderon, S J Koo, M Sinha, B A Luxon, N J Garg, J J Endsley
Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27731349/trpm2-regulates-txnip-mediated-nlrp3-inflammasome-activation-via-interaction-with-p47-phox-under-high-glucose-in-human-monocytic-cells
#14
Hisa Hui Ling Tseng, Chi Teng Vong, Yiu Wa Kwan, Simon Ming-Yuen Lee, Maggie Pui Man Hoi
Excessive production of reactive oxygen species (ROS) induced by hyperglycemia increased the secretion of interleukin-1β (IL-1β), which contributes to the pathogenesis of diabetes and its complications. Although high glucose (HG)-induced oxidative stress and aberrant Ca(2+) channels activity causes an increase in transmembrane Ca(2+) influx, however the relative contribution of Transient receptor potential (TRP) channels is not well studied. Here, we identified that HG (30 mM glucose for 48 h) induced the activation of the NLRP3-ASC inflammasome, leading to caspase-1 activation, and IL-1β and IL-18 secretion in human monocytic cell lines...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725089/diabetes-regulates-fructose-absorption-through-thioredoxin-interacting-protein
#15
James R Dotimas, Austin W Lee, Angela B Schmider, Shannon H Carroll, Anu Shah, Julide Bilen, Kayla R Elliott, Ronald B Myers, Roy J Soberman, Jun Yoshioka, Richard T Lee
Metabolic studies suggest that the absorptive capacity of the small intestine for fructose is limited, though the molecular mechanisms controlling this process remain unknown. Here we demonstrate that thioredoxin-interacting protein (Txnip), which regulates glucose homeostasis in mammals, binds to fructose transporters and promotes fructose absorption by the small intestine. Deletion of Txnip in mice reduced fructose transport into the peripheral bloodstream and liver, as well as the severity of adverse metabolic outcomes resulting from long-term fructose consumption...
October 11, 2016: ELife
https://www.readbyqxmd.com/read/27702549/thioredoxin-interacting-protein-mediates-lipid-induced-impairment-of-glucose-uptake-in-skeletal-muscle
#16
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27689322/case-specific-potentiation-of-glioblastoma-drugs-by-pterostilbene
#17
Linnéa Schmidt, Sathishkumar Baskaran, Patrik Johansson, Narendra Padhan, Damian Matuszewski, Lydia C Green, Ludmila Elfineh, Shimei Wee, Maria Häggblad, Ulf Martens, Bengt Westermark, Karin Forsberg-Nilsson, Lene Uhrbom, Lena Claesson-Welsh, Michael Andäng, Ida-Maria Sintorn, Bo Lundgren, Ingrid Lönnstedt, Cecilia Krona, Sven Nelander
Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27643555/resveratrol-ameliorates-lps-induced-acute-lung-injury-via-nlrp3-inflammasome-modulation
#18
Lei Jiang, Lei Zhang, Kai Kang, Dongsheng Fei, Rui Gong, Yanhui Cao, Shangha Pan, Mingran Zhao, Mingyan Zhao
NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI...
September 16, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27634649/identification-and-validation-of-seven-new-loci-showing-differential-dna-methylation-related-to-serum-lipid-profile-an-epigenome-wide-approach-the-regicor-study
#19
S Sayols-Baixeras, I Subirana, C Lluis-Ganella, F Civeira, J Roquer, A N Do, D Absher, D Muñoz, C Soriano-Tárraga, J Jiménez-Conde, J Ordovas, M Senti, S Aslibekyan, J Marrugat, D K Arnett, R Elosua
Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n=645) and validation in the Framingham Offspring Study (n=2,542)...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27626926/differential-lipotoxic-effects-of-palmitate-and-oleate-in-activated-human-hepatic-stellate-cells-and-epithelial-hepatoma-cells
#20
Alexandra M Hetherington, Cynthia G Sawyez, Emma Zilberman, Alexandra M Stoianov, Debra L Robson, Nica M Borradaile
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved...
2016: Cellular Physiology and Biochemistry
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