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https://www.readbyqxmd.com/read/29031535/baicalin-protects-aml-12-cells-from-lipotoxicity-via-the-suppression-of-er-stress-and-txnip-nlrp3-inflammasome-activation
#1
Junli Zhang, Haiming Zhang, Xiaoling Deng, Yuping Zhang, Keshu Xu
Baicalin (BA) is an active flavonoid compound originating from the root of Scutellaria baicalensis Georgi that has been reported to exert anti-inflammation and anti-oxidant effects in liver diseases with a long history. However, its protective and regulatory mechanisms on palmitic acid (PA) induced hepatocyte lipotoxicity remain elusive. In the present work, we investigated the cytoprotective effects of BA in AML-12 hepatocytes against lipotoxicity by inhibiting ER stress, oxidative stress and apoptosis. Our results demonstrated that ER stress was induced by 400 μM PA in AML-12 cells with elevated expression of ER stress marker IRE1α hyperphosphorylation...
October 11, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29031534/salidroside-alleviates-high-glucose-induced-oxidative-stress-and-extracellular-matrix-accumulation-in-rat-glomerular-mesangial-cells-by-the-txnip-nlrp3-inflammasome-pathway
#2
Shiying Wang, Xinxin Zhao, Suxia Yang, Baoping Chen, Jun Shi
Diabetic nephropathy (DN) is a metabolic disease characterized by mesangial cell proliferation and extracellular matrix (ECM) accumulation. Salidroside (SAL) is the major ingredient in Rhodiola rosea and possesses beneficial effects on DN. This study aimed to evaluate the effect of SAL on high glucose (HG)-induced oxidative stress and ECM accumulation and the underlying mechanism. Rat glomerular mesangial cells HBZY-1 were induced by high glucose (HG) in the presence or absence of SAL. Cell proliferation was measured by CCK-8 assay...
October 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28988346/lipid-environment-induces-er-stress-txnip-expression-and-inflammation-in-immune-cells-of-individuals-with-type-2-diabetes
#3
Anaïs Szpigel, Isabelle Hainault, Aurélie Carlier, Nicolas Venteclef, Anne-Françoise Batto, Eric Hajduch, Catherine Bernard, Alain Ktorza, Jean-François Gautier, Pascal Ferré, Olivier Bourron, Fabienne Foufelle
AIMS/HYPOTHESIS: Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation...
October 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28980863/addition-of-exogenous-sodium-palmitate-increases-the-iapp-insulin-mrna-ratio-via-gpr40-in-human-endoc-%C3%AE-h1-cells
#4
Camilla Krizhanovskii, Rikard G Fred, Marie E Oskarsson, Gunilla T Westermark, Nils Welsh
BACKGROUND: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells. METHODS: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms...
October 5, 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/28966753/short-term-high-dose-of-quercetin-and-resveratrol-alters-aging-markers-in-human-kidney-cells
#5
Fatemeh Abharzanjani, Mohammad Afshar, Mina Hemmati, Maryam Moossavi
BACKGROUND: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. METHODS: Human embryonic kidney cell (HEK-293) was cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 100 mM (18 mg/L) for 24 h. The cells were treated with resveratrol (2...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28963352/mtor-and-hdac-inhibitors-converge-on-the-txnip-thioredoxin-pathway-to-cause-catastrophic-oxidative-stress-and-regression-of-ras-driven-tumors
#6
Clare F Malone, Chloe Emerson, Rachel Ingraham, William Barbosa, Stephanie Guerra, Haejin Yoon, Lin L Liu, Franziska Michor, Marcia Haigis, Kay F Macleod, Ophélia Maertens, Karen Cichowski
While agents that inhibit specific oncogenic kinases have been successful in a subset of cancers, there are currently few treatment options for malignancies that lack a targetable oncogenic driver. Nevertheless, during tumor evolution cancers engage a variety of protective pathways, which may provide alternative actionable dependencies. Here we identify a promising combination therapy that kills NF1-mutant tumors by triggering catastrophic oxidative stress. Specifically, we show that mTOR and HDAC inhibitors kill aggressive nervous system malignancies and shrink tumors in vivo by converging on the TXNIP/thioredoxin anti-oxidant pathway, through cooperative effects on chromatin and transcription...
September 29, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28944891/thioredoxin-is-implicated-in-the-anti%C3%A2-apoptotic-effects-of-grape-seed-proanthocyanidin-extract-during-hyperglycemia
#7
Xiang Ren, Heyuan Lu, Nina Wang, Chenghong Zhang, Yunpeng Ji, Shiqi Cui, Yichen Dong, Kaiyuan Yang, Mengyi Du, Fengsheng Diao, Li Kong
Diabetic retinopathy has long been recognized as a microvascular disease, however, recent research has indicated that diabetic retinopathy may also be considered a neurodegenerative disease. The elucidation of the molecular mechanisms underlying the development of diabetic retinopathy is imperative for the development of preventive and treatment strategies for patients with diabetes. In the present study, grape seed proanthocyanidin extract (GSPE) was used to upregulate the expression of thioredoxin (Trx), in order to evaluate its potential as a novel agent for the prevention and treatment of neurodegenerative diseases, including diabetic retinopathy...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28938188/induction-of-heme-oxygenas-1-attenuates-nlrp3-inflammasome-activation-in-lipopolysaccharide-induced-mastitis-in-mice
#8
Hu Xiaoyu, Hongbin Si, Shumin Li, Wenqing Wang, Jian Guo, Yanyi Li, Yongguo Cao, Yunhe Fu, Naisheng Zhang
Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1β, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#9
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28918907/thioredoxin-promotes-survival-signaling-events-under-nitrosative-oxidative-stress-associated-with-cancer-development
#10
REVIEW
Hugo P Monteiro, Fernando T Ogata, Arnold Stern
Accumulating mutations may drive cells into the acquisition of abnormal phenotypes that are characteristic of cancer cells. Cancer cells feature profound alterations in proliferation programs that result in a new population of cells that overrides normal tissue construction and maintenance programs. To achieve this goal, cancer cells are endowed with up regulated survival signaling pathways. They also must counteract the cytotoxic effects of high levels of nitric oxide (NO) and of reactive oxygen species (ROS), which are by products of cancer cell growth...
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28918467/anisodamine-inhibits-endoplasmic-reticulum-stress-associated-txnip-nlrp3-inflammasome-activation-in-rhabdomyolysis-induced-acute-kidney-injury
#11
Xiaopeng Yuan, Yitao Zheng, Chuanbao Chen, Changxi Wang
Anisodamine protects against free radical-induced cellular damage. This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6 J mice, TXNIP(-/-) and NLRP3 (-/-) (both were C57BL/6 J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, and interleukin (IL-1α, IL-1β, and IL-18) were detected...
September 16, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28890350/thioredoxin-interacting-protein-promotes-high-glucose-induced-macrovascular-endothelial-dysfunction
#12
Xiaoyu Li, Karen L Kover, Daniel P Heruth, Dara J Watkins, Yanchun Guo, Wayne V Moore, Luke G He, Mengwei Zang, Mark A Clements, Yun Yan
Thioredoxin-interacting protein (TXNIP) emerges as a central regulator for glucose homeostasis, which goes awry in diabetic subjects. Endothelial dysfunction is considered the earliest detectable stage of cardiovascular disease (CVD), a major complication of diabetes. Here, we hypothesize that TXNIP may promote endothelial dysfunction seen in Type 1 diabetes mellitus (T1D). Using a T1D-like rat model, we found that diabetic rats showed significantly higher TXNIP mRNA and protein levels in peripheral blood, compared to their non-diabetic counterparts...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28871193/estradiol-regulates-txnip-and-prevents-intermittent-hypoxia-induced-vascular-injury
#13
Xiao Fei Lan, Xiu Juan Zhang, Ying Ni Lin, Qiong Wang, Hua Jun Xu, Li Na Zhou, Pei Li Chen, Qing Yun Li
Chronic intermittent hypoxia (IH) contributes to obstructive sleep apnea (OSA)-related cardiovascular diseases through increasing oxidative stress. It has been widely recognized that estradiol decreases the risk for cardiovascular disease, but the estrogen replacement therapy is limited for its side effects. Thioredoxin (Trx) and its endogenous inhibitor, thioredoxin-interacting protein (Txnip), are associated with the protective effect of estradiol in some conditions. In this study, we aimed to explore whether estradiol could protect against IH-induced vascular injury, and the possible effect of Trx-1/Txnip in this process...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851669/nrf2-inhibits-nlrp3-inflammasome-activation-through-regulating-trx1-txnip-complex-in-cerebral-ischemia-reperfusion-injury
#14
Yanghao Hou, Yueting Wang, Qi He, Lingyu Li, Hui Xie, Yong Zhao, Jing Zhao
The nod-like receptor protein 3 (NLRP3) inflammasome has a critical role in inflammation damage in ischemic injury, and the activation of the inflammasome is closely related to the interaction with thioredoxin interacting protein (TXNIP), which dissociates from the thioredoxin1 (Trx1)/TXNIP complex under oxidative stress. However, the negative regulator of NLRP3 inflammasome activation has not been fully investigated. Nuclear factor erythroid 2-related factor 2 (Nrf2) takes on a critical part in the antioxidant stress system, that controls the driven genes of antioxidant response element (ARE)...
January 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28844667/thioredoxin-1-redox-factor-1-and-thioredoxin-interacting-protein-mrnas-are-differentially-expressed-in-multiple-sclerosis-patients-exposed-and-non-exposed-to-interferon-and-immunosuppressive-treatments
#15
Elham Mahmoudian, Ahad Khalilnezhad, Kurosh Gharagozli, Davar Amani
BACKGROUND: Oxidative stress is closely linked to inflammation in neurodegenerative diseases. We aimed to investigate the expression of redox system genes in Multiple Sclerosis (MS) patients either exposed or not exposed to conventional treatments. METHODS: Forty-four MS patients were divided into three groups: newly diagnosed (Group 1), receiving interferon (Group 2) and receiving immunosuppressive drugs (Group 3). Also, 15 healthy controls were enrolled. The mRNA expression of TRX1, TXNRD1, TRX2, TXNRD2, TXNIP, and APEX1 genes in peripheral blood mononuclear cells (PBMCs) was assessed by relative quantitative real-time PCR...
November 15, 2017: Gene
https://www.readbyqxmd.com/read/28843855/metformin-protects-against-retinal-cell-death-in-diabetic-mice
#16
Yoon Sook Kim, Minjun Kim, Mee Young Choi, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Seong-Jae Kim, Ji-Myong Yoo, Wan Sung Choi
Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. Metformin was orally administered to control mice or mice with streptozotocin-induced diabetes. Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls...
August 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28843270/thioredoxin-interact-ing-pro-t-e-in-txnip-and-transglutaminase-2-tgm2-expression-in-meningiomas-of-different-grades-and-the-role-of-their-expression-in-meningioma-recurrence-and-prognosis
#17
Ola A Harb, Walid SH Elsayed, Eman I Ismail, Mostafa M Toam, Mohamed G Ammar
Background: Meningiomas are common central nervous system (CNS) tumors that account for thirty percent of primary intracranial tumors.. The accuracy of predicting meningioma recurrence and progression is not enough. So, there is a real need for discovering recent factors for identification of the relapse risk, progression rates, which patients will need aggressive treatment and predicting and improving patients’ survival. Thioredoxin-interacting-protein [TXNIP] is an alpha-arrestin-protein family member that is mapped on chromosome 1-q21–22 and is found to participate in cellular redox reactions regulations and control...
August 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28840690/-pro-inflammatory-mechanism-of-lectin-from-pinellia-pedatisecta-on-macrophage
#18
Shan-Hu Mao, Hong-Li Yu, Hao Wu, Wei Wang, Xiao-Nan Li
To investigate the mechanism of lectin from Pinellia pedatisecta(PPL) on macrophage-induced inflammation and its association with inflammatory corpuscles NLRP3. Lectin from P. pedatisecta was isolated and purified by gel chromatography, and its purity was analyzed by using SDS-PAGE gel electrophoresis. ELISA was used to investigate the effect of PPL on inflammatory cytokines released by macrophages, with IL-1β as indicators;and fluorescence probe DCFH-DA fluorometer was used to determine changes in active oxygen ROS of macrophages after application of lectin from P...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#19
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28817808/ppar%C3%AE-agonist-stimulated-angiogenesis-by-improving-endothelial-precursor-cell-function-via-a-nlrp3-inflammasome-pathway
#20
Yaping Deng, Xue Han, Zheng Yao, Yuannan Sun, Jiawen Yu, Jian Cai, Guofei Ren, Guojun Jiang, Feng Han
BACKGROUND: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators-activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice...
August 16, 2017: Cellular Physiology and Biochemistry
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