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https://www.readbyqxmd.com/read/28427200/idh1-r132h-mutation-regulates-glioma-chemosensitivity-through-nrf2-pathway
#1
Kaishu Li, Leping Ouyang, Mingliang He, Ming Luo, Wangqing Cai, Yalin Tu, Rongbiao Pi, Anmin Liu
PURPOSE: Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. METHODS: Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421738/targeting-the-nrf2-amyloid-beta-liaison-in-alzheimer-s-disease-a-rational-approach
#2
Elena Simoni, Melania M Serafini, Roberta Caporaso, Chiara Marchetti, Marco Racchi, Anna Minarini, Manuela Bartolini, Cristina Lanni, Michela Rosini
Amyloid is a prominent feature of Alzheimer's disease (AD). Yet, a linear linkage between amyloid-β peptide (Aβ) and the disease onset and progression has recently been questioned. In this context, the crucial partnership between Aβ and Nrf2 pathways is acquiring paramount importance, offering prospects for deciphering the Aβ-centered disease network. Here, we report on a new class of anti-aggregating agents rationally designed to simultaneously activate transcription-based antioxidant responses, whose lead 1 showed interesting properties in a preliminary investigation...
April 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28416455/protection-from-cr-vi-induced-malignant-cell-transformation-and-tumorigenesis-of-cr-vi-transformed-cells-by-luteolin-through-nrf2-signaling
#3
Young-Ok Son, Poyil Pratheeshkumar, Yuting Wang, Donghern Kim, Zhuo Zhang, Xianglin Shi
Cr(VI) is a well known environmental carcinogen, but its mechanism of action and the measures required to mitigate its effects remain to be investigated. Our previous studies showed that exposure of human bronchial epithelial (BEAS-2B) cells to Cr(VI) caused malignant transformation, that these transformed cells progressed through tumorigenesis, and that luteolin, a natural compound, inhibited both of these processes. The present study investigates the underlying mechanisms by which luteolin protects cells against Cr(VI)-induced transformation and tumorigenesis...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28412655/parkinson-s-disease-and-pesticides-a-meta-analysis-of-disease-connection-and-genetic-alterations
#4
Hussien Ahmed, Abdelrahman Ibrahim Abushouk, Mohamed Gabr, Ahmed Negida, Mohamed M Abdel-Daim
Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5...
April 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28411284/mitochondrial-power-drives-tamoxifen-resistance-nqo1-and-gclc-are-new-therapeutic-targets-in-breast-cancer
#5
Marco Fiorillo, Federica Sotgia, Diego Sisci, Anna Rita Cappello, Michael P Lisanti
Here, we identified two new molecular targets, which are functionally sufficient to metabolically confer the tamoxifen-resistance phenotype in human breast cancer cells. Briefly, ~20 proteins were first selected as potential candidates, based on unbiased proteomics analysis, using tamoxifen-resistant cell lines. Then, the cDNAs of the most promising candidates were systematically transduced into MCF-7 cells. Remarkably, NQO1 and GCLC were both functionally sufficient to autonomously confer a tamoxifen-resistant metabolic phenotype, characterized by i) increased mitochondrial biogenesis, ii) increased ATP production and iii) reduced glutathione levels...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28395199/design-synthesis-and-biological-evaluation-of-nad-p-h-quinone-oxidoreductase-nqo1-targeted-oridonin-prodrugs-possessing-indolequinone-moiety-for-hypoxia-selective-activation
#6
Shengtao Xu, Hong Yao, Lingling Pei, Mei Hu, Dahong Li, Yangyi Qiu, Guangyu Wang, Liang Wu, Hequan Yao, Zheying Zhu, Jinyi Xu
The enzyme NQO1 is a potential target for selective cancer therapy due to its overexpression in certain hypoxic tumors. A series of prodrugs possessing a variety of cytotoxic diterpenoids (oridonin and its analogues) as the leaving groups activated by NQO1 were synthesized by functionalization of 3-(hydroxymethyl)indolequinone, which is a good substrate of NQO1. The target compounds (29a-m) exhibited relatively higher antiproliferative activities against NQO1-rich human colon carcinoma cells (HT-29) and human lung carcinoma (A549) cells (IC50 = 0...
March 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28392465/l-carnitine-preserves-cardiac-function-by-activating-p38-mapk-nrf2-signalling-in-hearts-exposed-to-irradiation
#7
Zhigang Fan, Yang Han, Yuanpeng Ye, Chao Liu, Hui Cai
Radiation-induced heart damage (RIHD) is now considered to be one of the causes of mortality in cancer patients undergoing radiotherapy. Cardiac function impairments are clinical manifestations of RIHD. L-carnitine shows protective effects against irradiation and heart disease. This study was aimed to investigate the cardioprotective effects and potential molecular mechanisms of L-carnitine against RIHD. Mouse hearts were exposed to γ-radiation to induce RIHD. L-carnitine at doses of 100mg/Kg and 200mg/Kg was used to treat animals intraperitoneally...
April 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28390311/metformin-mitigates-carbon-tetrachloride-induced-tgf-%C3%AE-1-smad3-signaling-and-liver-fibrosis-in-mice
#8
Kerui Fan, Kejia Wu, Ling Lin, Pu Ge, Jie Dai, Xiaojiao He, Kai Hu, Li Zhang
Increasing evidence suggests that the widely used antidiabetic drug metformin have an extensive therapeutic range beyond hypoglycemic therapy. We previously found that metformin significantly attenuated acute hepatitis. The present study investigated the potential effects of metformin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The results indicated that treatment with metformin suppressed CCl4-induced elevation of liver index, formation of fibrotic septa, accumulation of connective tissue and upregulation of collagen I...
April 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28382390/protective-effect-of-glutamine-on-the-main-and-adjacent-organs-damaged-by-ischemia-reperfusion-in-rats
#9
Renata Minuzzo Hartmann, Francielli Licks, Elizângela Gonçalves Schemitt, Josieli Raskopf Colares, Mariana do Couto Soares, Gilmara Pandolfo Zabot, Henrique Sarubbi Fillmann, Norma Possa Marroni
Intestinal ischemia and reperfusion (I/R) causes cellular and tissue damage to the intestine and remote organs such as the liver. Increased production of ROS and nitric oxide and dysregulation of cytoprotective enzymes may be involved in intestinal I/R. The aim was to evaluate the protective effects of glutamine on the intestine and liver of rats with intestinal I/R injury. Twenty male Wistar rats (300 g) were divided into four groups: sham-operated (SO), glutamine + SO (G + SO), I/R, and glutamine + I/R (G + I/R)...
April 5, 2017: Protoplasma
https://www.readbyqxmd.com/read/28381791/anti-oxidative-activity-of-hydrolysate-from-rice-bran-protein-in-hepg2-cells
#10
Chie Moritani, Kayoko Kawakami, Akiko Fujita, Koji Kawakami, Tadashi Hatanaka, Seiji Tsuboi
Glutathione (GSH) is an ubiquitous thiol-containing tripeptide, which plays important roles in cellular protection from oxidative stress. In our search for a dietary source that can increase glutathione (GSH) levels, we discovered that a 24 h treatment of HepG2 cells with rice bran protein hydrolysate (RBPH), prepared by Umamizyme G-catalyzed hydrolysis, increased the GSH content in a dose-dependent manner. RBPH elevated the expression levels ofγ-glutamylcysteine synthetase (γ-GCS), which constitutes the rate-limiting enzyme of GSH synthesis, and of another two enzymes, hemeoxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase1 (NQO1)...
April 6, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28370349/the-nuclear-factor-erythroid-derived-2-like-2-nrf2-antioxidant-response-promotes-melanocyte-viability-and-reduces-toxicity-of-the-vitiligo-inducing-phenol-monobenzone
#11
Omotayo A Arowojolu, Seth J Orlow, Nada Elbuluk, Prashiela Manga
Vitiligo, characterized by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterized. We hypothesized that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity...
March 31, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28367064/role-of-nrf2-signaling-pathway-in-the-radiation-tolerance-of-patients-with-head-and-neck-squamous-cell-carcinoma-an-in-vivo-and-in-vitro-study
#12
Tao Wang, Peng Hu, Bo Li, Jun-Peng Zhang, Yu-Feng Cheng, Ye-Min Liang
We aimed to investigate the relationship between the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the radiation tolerance of patients with head and neck squamous cell carcinoma (HNSCC). From January 2015 to January 2016, 117 patients with HNSCC were enrolled in our study and assigned into the sensitive and tolerance groups based on curative effect. Immunohistochemistry (IHC) was conducted to measure protein expressions of Nrf2, heme oxygenase-1 (HO1), NADPH quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28367062/associations-of-nqo1-c609t-and-nqo1-c465t-polymorphisms-with-acute-leukemia-risk-a-prisma-compliant-meta-analysis
#13
Hairong He, Xiaoyu Zhai, Xiaomin Liu, Jie Zheng, Yajing Zhai, Fan Gao, Yonghua Chen, Jun Lu
OBJECTIVE: The NAD(P)H:quinone oxidoreductase (NQO1) C609T and C465T polymorphisms have been widely thought to be associated with the risk of acute leukemia (AL) in recent years, but the correlations are still unclear. A meta-analysis is generally acknowledged as one of the best methods for secondary research, and so it was applied in this study with the aim of elucidating how the NQO1 C609T and C465T polymorphisms are related to the risk of AL. METHODS: Relevant studies were searched in the PubMed, EMBASE, CNKI, and Wanfang databases, and the obtained data were analyzed using Stata (version 12...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28357584/association-of-cytochrome-p4502e1-and-nad-p-h-quinone-oxidoreductase-1-genetic-polymorphisms-with-susceptibility-to-large-artery-atherosclerotic-ischemic-stroke-a-case-control-study-in-the-turkish-population
#14
Aysun Türkanoğlu Özçelik, Birsen Can Demirdöğen, Şeref Demirkaya, Orhan Adalı
Stroke, a major cause of death and disability, is described as interruption or severe reduction of blood flow in cerebral arteries. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and carotid atherosclerosis is a risk factor for stroke. Combination of multiple environmental and genetic risk factors is thought to increase stroke. Therefore, investigation of the polymorphisms of enzymes is of crucial importance to determine the molecular etiology of the disease. To test this hypothesis, we performed a case-control study in which we compared the distribution of CYP2E1 and NQO1 genotypes between 245 large artery atherosclerotic ischemic stroke patients and 145 controls, using PCR-RFLP...
March 29, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28346733/the-ontogeny-and-population-variability-of-human-hepatic-dihydronicotinamide-riboside-quinone-oxidoreductase-nqo2
#15
Zoe Riches, Yuejian Liu, Jacob M Berman, Gurinder Walia, Abby C Collier
Dihydronicotinamide riboside:quinone oxidoreductase (NQO2) is an enzyme that performs reduction reactions involved in antioxidant defense. We hypothesized that NQO2 hepatic drug clearance would develop in children over time, similar to NQO1. Using human liver cytosol (n = 117), the effects of age, sex, ethnicity, and weight on NQO2 expression and activity were probed. No significant correlations were observed. Biochemical activity of NQO2 was as high at birth as in adults (0.23 ± 0.04 nmol/min/mg protein, mean ± SEM, range 0-1...
March 27, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#16
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28345875/reactive-oxygen-species-synergize-to-potently-and-selectively-induce-cancer-cell-death
#17
Hyang Yeon Lee, Elizabeth I Parkinson, Carlotta Granchi, Ilaria Paterni, Dipak Panigrahy, Pankaj Seth, Filippo Minutolo, Paul J Hergenrother
A distinctive feature of cancer cells is their elevated levels of reactive oxygen species (ROS), a trait that can cause cancer cells to be more sensitive to ROS-inducing agents than normal cells. ROS take several forms, each with different reactivity and downstream consequence. Here we show that simultaneous generation of superoxide and hydrogen peroxide within cancer cells results in significant synergy, potently and selectively causing cancer cell death. In these experiments superoxide is generated using the NAD(P)H quinone oxidoreductase 1 (NQO1) substrate deoxynyboquinone (DNQ), and hydrogen peroxide is generated using the lactate dehydrogenase A (LDH-A) inhibitor NHI-Glc-2...
April 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28337145/dioscin-protects-anit-induced-intrahepatic-cholestasis-through-regulating-transporters-apoptosis-and-oxidative-stress
#18
Hong Yao, Youwei Xu, Lianhong Yin, Xufeng Tao, Lina Xu, Yan Qi, Xu Han, Pengyuan Sun, Kexin Liu, Jinyong Peng
Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28323302/vegetable-and-fruit-juice-enhances-antioxidant-capacity-and-regulates-antioxidant-gene-expression-in-rat-liver-brain-and-colon
#19
Linhong Yuan, Jinmeng Liu, Jie Zhen, Yao Xu, Shuying Chen, Nicholas Van Halm-Lutterodt, Rong Xiao
To explore the effect of fruit and vegetable (FV) juice on biomarkers of oxidative damage and antioxidant gene expression in rats, 36 adult male Wistar rats were randomly divided into control, low FV juice dosage or high FV juice dosage treatment groups. The rats were given freshly extracted FV juice or the same volume of saline water daily for five weeks. After intervention, serum and tissues specimens were collected for biomarker and gene expression measurement. FV juice intervention increased total antioxidant capacity, glutathione, vitamin C, β-carotene, total polyphenols, flavonoids levels andglutathione peroxidaseenzyme activity in rat serum or tissues (p < 0...
March 20, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28300285/hx-1171-a-novel-nrf2-activator-induces-nqo1-and-hmox1-expression
#20
Jimin Kim, Su-Hyun Shin, Young-Eun Ko, Tokutaro Miki, Heung-Mo Bae, Jong-Koo Kang, Jae Wha Kim
HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a novel synthesized vitamin E derivative, which reportedly has positive effects on various diseases and conditions, such as liver fibrosis, hepatic cirrhosis, and cancer. In this study, we analyzed the transcriptional activity induced by HX-1171. Results from reverse transcription polymerase chain reaction and promoter assays reveal that HX-1171 increased the expression of NQO1 and HMOX1, encoding antioxidant-related enzymes, in A549 human lung epithelial cells...
March 16, 2017: Journal of Cellular Biochemistry
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