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Yuqing Yang, Francisco Fuentes, Limin Shu, Chao Wang, Doug Pung, Wenji Li, Chengyue Zhang, Yue Guo, Ah-Ng Kong
Astaxanthin (AST), a red dietary carotenoid, has synergistic antioxidant effects with polyunsaturated fatty acids at low concentrations via Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2)/antioxidant response element (ARE) signaling. In addition, chromatin remodeling and DNA methylation-based gene silencing represent a common mechanism in prostate carcinogenesis and tumor progression from normal cells to pre-initiated cells and ultimately to invasive carcinoma. Therefore, the control of epigenetic modification and the transcriptional/translational control of the activation of Nrf2 and Nrf2-target genes, including glutathione S-transferases (GSTs), appear to be an important mechanism that protects cells against injuries from oxidative stress and cancer development...
December 2, 2016: AAPS Journal
Yibin Liu, Chen Song, Ioannis Ladas, Mariana Fitarelli-Kiehl, G Mike Makrigiorgos
Aberrant methylation changes, often present in a minor allelic fraction in clinical samples such as plasma-circulating DNA (cfDNA), are potentially powerful prognostic and predictive biomarkers in human disease including cancer. We report on a novel, highly-multiplexed approach to facilitate analysis of clinically useful methylation changes in minor DNA populations. Methylation Specific Nuclease-assisted Minor-allele Enrichment (MS-NaME) employs a double-strand-specific DNA nuclease (DSN) to remove excess DNA with normal methylation patterns...
November 29, 2016: Nucleic Acids Research
Natalia Weich, Alejandro Roisman, Belén Cerliani, Hilda V Aráoz, Lilien Chertkoff, Silvina M Richard, Irma Slavutsky, Irene B Larripa, Ariela F Fundia
BACKGROUND: Glutathione S-transferases (GSTs) are drug-metabolising enzymes involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free radicals. Polymorphisms of GST genes contribute to inter-individual and population variability in the susceptibility to environmental risk factors, cancer predisposition and pharmacotherapy responses. However, data about GST variability in Argentina are lacking. AIM: The purpose was to determine the prevalence of GSTM1, GSTT1 and GSTP1 polymorphisms in the general population from a central region of Argentina and to perform inter-population comparisons...
November 28, 2016: Annals of Human Biology
Huang Ruihua, Zhang Mengyi, Zhao Chong, Qiu Meng, Ma Xin, Tang Qiulin, Bi Feng, Liu Ming
Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment in early stage CRC, chemotherapy is usually given to prolong the overall survival and improve the quality of life for metastatic colorectal cancer (mCRC). But drug resistance is one of the major hurdles of mCRC treatment, and the underlying mechanisms are still largely unknown. In this study, we show that, compared with parental cells, RhoA is up-regulated in irinotecan (CPT-11)-resistant CRC cells...
November 24, 2016: Oncotarget
Jill A Madden, Porsha Q Thomas, Aileen F Keating
Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide. Postnatal day 4 Fisher 344 rat ovaries were exposed to vehicle control (1% DMSO) or PM (60μM)±LY294002 or rapamycin for 2 or 4 d. Transmission election microscopy revealed abnormally large golgi apparatus and electron dense mitochondria in PM-exposed ovaries prior to and at the time of follicle depletion. PM exposure increased (P<0.05) mRNA abundance of Bbc3, Cdkn1a, Ctfr, Edn1, Gstp1, Nqo1, Tlr4, Tnfrsfla, Txnrd1 and decreased (P<0...
November 22, 2016: Reproductive Toxicology
Tristan M Sissung, John Deeken, Crystal R Leibrand, Douglas K Price, Sheryl Ehrlich, Seth M Steinberg, David J Liewehr, William Dahut, William D Figg
AIM: Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). MATERIALS & METHODS: A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. RESULTS: No relation to risk was found...
November 24, 2016: Pharmacogenomics
Hugo Villamil-Ramírez, Paola León-Mimila, Luis R Macias-Kauffer, Adrián Canizalez-Román, Marisela Villalobos-Comparán, Nidia León-Sicairos, Joel Vega-Badillo, Fausto Sánchez-Muñoz, Blanca López-Contreras, Sofía Morán-Ramos, Teresa Villarreal-Molina, Luis C Zurita, Francisco Campos-Pérez, Adriana Huertas-Vazquez, Rafael Bojalil, Sandra Romero-Hidalgo, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros
Obesity is a major public health concern in Mexico and worldwide. Although the estimated heritability is high, common variants identified by genome-wide association studies explain only a small proportion of this heritability. A combination of linkage and association strategies could be a more robust and powerful approach to identify other obesity-susceptibility variants. We thus sought to identify novel genetic variants associated with obesity-related traits in the Mexican population by combining these methods...
November 24, 2016: Journal of Human Genetics
Gayan Bowatte, Caroline J Lodge, Jennifer L Perret, Melanie C Matheson, Shyamali C Dharmage
PURPOSE OF REVIEW: The purpose of this review is to summarize the evidence from recently published original studies investigating how glutathione S-transferase (GST) gene polymorphisms modify the impact of air pollution on asthma, allergic diseases, and lung function. RECENT FINDINGS: Current studies in epidemiological and controlled human experiments found evidence to suggest that GSTs modify the impact of air pollution exposure on respiratory diseases and allergies...
November 2016: Current Allergy and Asthma Reports
Wayne Harshbarger, Sudershan Gondi, Scott B Ficarro, John Hunter, Durga Udayakumar, Deepak Gurbani, William Singer, Yan Liu, Lianbo Li, Jarrod A Marto, Kenneth D Westover
Glutathione S-transferase pi 1 (GSTP1), is frequently overexpressed in cancerous tumors and is a putative target of the plant compound piperlongumine (PL), which contains two reactive olefins and inhibits proliferation in cancer cells but not normal cells. PL exposure of cancer cells results in increased reactive oxygen species and decreased glutathione (GSH). This data in tandem with other information led to the conclusion that PL inhibits GSTP1, which forms covalent bonds between GSH and various electrophilic compounds, through covalent adduct formation at PLs C7-C8 olefin, while PLs C2-C3 olefin was postulated to react with GSH...
November 21, 2016: Journal of Biological Chemistry
Ricardo Sánchez-Rodríguez, Julia Esperanza Torres-Mena, Valeria Quintanar-Jurado, Victoria Chagoya-Hazas, Emilio Rojas Del Castillo, Luis Del Pozo Yauner, Saul Villa-Treviño, Julio Isael Pérez-Carreón
Prostaglandin reductase-1 (Ptgr1) is an alkenal/one oxidoreductase that is involved in the catabolism of eicosanoids and lipid peroxidation such as 4-hydroxynonenal (4-HNE). Recently, we reported that Ptgr1 is overexpressed in human clinical and experimentally induced samples of hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated and its role in carcinogenesis are not yet known. Here, we studied parameters associated with antioxidant responses and the mechanisms underlying the induction of Ptgr1 expression by the activation of Nuclear Factor (erythroid-derived-2)-like-2 (NRF2)...
November 18, 2016: Free Radical Biology & Medicine
Hiu Chuen Lok, Sumit Sahni, Patric J Jansson, Zaklina Kovacevic, Clare L Hawkins, Des R Richardson
Nitric oxide (NO) is integral to macrophage cytotoxicity against tumors due to its ability to induce iron release from cancer cells. However, the mechanism how activated macrophages protect themselves from endogenous NO remains unknown. We previously demonstrated using tumor cells that glutathione S-transferase P1 (GSTP1) sequesters NO as dinitrosyl-dithiol iron complexes (DNICs) and inhibits NO-mediated iron release from cells via the transporter, multidrug resistance protein 1 (MRP1/ABCC1). These prior studies also showed that MRP1 and GSTP1 protect tumor cells against NO cytotoxicity, which parallels their roles in defending cancer cells from cytotoxic drugs...
November 19, 2016: Journal of Biological Chemistry
Lorien J Parker, Alessio Bocedi, David B Ascher, Jade B Aitken, Hugh H Harris, Mario Lo Bello, Giorgio Ricci, Craig J Morton, Michael W Parker
Arsenic-based compounds are paradoxically both poisons and drugs. Glutathione transferase (GSTP1-1) is a major factor in resistance to such drugs. Here we describe using crystallography, X-ray absorption spectroscopy, mutagenesis, mass spectrometry and kinetic studies how GSTP1-1 recognizes the drug phenylarsine oxide (PAO). In conditions of cellular stress where glutathione (GSH) levels are low, PAO crosslinks C47 to C101 of the opposing monomer, a distance of 19.9 Å, and causes a dramatic widening of the dimer interface by ∼10 Å...
November 18, 2016: Protein Science: a Publication of the Protein Society
Cheng Zhang, Jinyun Li, Tao Huang, Shiwei Duan, Dongjun Dai, Danjie Jiang, Xinbing Sui, Da Li, Yidan Chen, Fei Ding, Changxin Huang, Gongying Chen, Kaifeng Wang
DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC...
November 8, 2016: Oncotarget
Mohammad H Rahbar, Maureen Samms-Vaughan, Meagan R Pitcher, Jan Bressler, Manouchehr Hessabi, Katherine A Loveland, MacKinsey A Christian, Megan L Grove, Sydonnie Shakespeare-Pellington, Compton Beecher, Wayne McLaughlin, Eric Boerwinkle
Aluminum is a neurotoxic metal with known health effects in animals and humans. Glutathione-S-transferase (GST) genes and enzymes play a major role in detoxification of several heavy metals. Besides a direct relationship with oxidative stress; aluminum decreases GST enzyme activities. Using data from 116 Jamaican children; age 2-8 years; with Autism Spectrum Disorder (ASD) and 116 sex- and age-matched typically developing (TD) children; we investigated the association of polymorphisms in three GST genes (GSTP1; GSTM1; and GSTT1) with mean blood aluminum concentrations in children with and without ASD...
November 8, 2016: International Journal of Environmental Research and Public Health
Huijie Gao, Chao Liu, Ping Lin, Luo Xu, Xiao Li, Yujie Chen, Baohua Cheng, Aiqin Li, Shiguo Liu
BACKGROUND/AIMS: Increasing evidence shows that oxidative stress plays an important part in the pathophysiological mechanisms of preeclampsia (PE). Polymorphic variants of oxidative stress-related candidate genes GST1 and GPX1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the associational analysis between GSTP1 and GPX1 single nucleotide polymorphisms (SNPs) and susceptibility to PE in Chinese Han women. METHODS: DNA from 1130 PE patients and 1226 healthy individuals was genotyped for SNPs rs1695 in GSTP1 and rs1050450 in GPX1 using a predesigned TaqMan SNP genotyping assay...
2016: Cellular Physiology and Biochemistry
H X Liu, J Li, B G Ye
Lung cancer is a common malignant tumor that is characterized by high morbidity and poor prognosis. Studies suggest that an individual's genetic background affects the risk of developing lung cancer. Therefore, we investigated the relationship between gene polymorphisms and susceptibility to lung cancer. We recruited 308 primary lung cancer patients as subjects and 253 healthy adults as controls. After extraction of DNA from blood samples, gene polymorphisms in CYP1A1, GSTP1, ERCC2, XRCC1, and XRCC3 were investigated by polymerase chain reaction and restriction fragment length polymorphism...
November 3, 2016: Genetics and Molecular Research: GMR
Alessio Bocedi, Raffaele Fabrini, Mario Lo Bello, Anna Maria Caccuri, Giorgio Federici, Bengt Mannervik, Athel Cornish-Bowden, Giorgio Ricci
Negative cooperativity in enzyme reactions - in which the first event makes subsequent events less favorable - is sometimes well understood at the molecular level, but its physiological role has often been obscure. Negative cooperativity occurs in human glutathione transferase (GST) GSTP1-1 when it binds and neutralizes a toxic nitric oxide adduct, the dinitrosyl-diglutathionyl iron complex (DNDGIC). However, the generality of this behavior across the divergent GST family and its evolutionary significance were unclear...
November 4, 2016: Journal of Biological Chemistry
Roderick J Tan, Dionysios V Chartoumpekis, Brittney M Rush, Dong Zhou, Haiyan Fu, Thomas W Kensler, Youhua Liu
The Keap1/Nrf2 pathway is a master regulator of antioxidant, anti-inflammatory, and other cytoprotective mechanisms important in protection from kidney disease. For the first time in kidney disease, we describe the use of Keap1 hypomorphic mice, which possess Nrf2 hyperactivation. We exposed these mice and wild type controls to ischemia/reperfusion injury (IRI). The initial tubular injury at 24 hours post-IRI appeared to be unaffected, with the only observed difference being a decrease in inflammatory cytokine expression in the hypomorphs...
November 2, 2016: Scientific Reports
Xiangzhen Kong, Zihao Li, Xian Li
Several studies have investigated the effects of polymorphisms in the GSTP1, GSTT1, and GSTM1 genes on responsiveness to chemotherapy in breast cancer, but the results have been inconsistent. The aim of this study was to determine the association between polymorphisms of GSTP1, GSTT1, and GSTM1 genes and response to chemotherapy in patients with breast cancer. The relevant studies were retrieved from PubMed, Embase, ISI Web of Knowledge, China National Knowledge Infrastructure, and Wanfang databases. The articles evaluating the correlations between response to chemotherapy and GSTP1, GSTT1, and GSTM1 polymorphisms in breast cancer patients were comprehensively reviewed...
October 26, 2016: Cancer Chemotherapy and Pharmacology
Sedar Karakurt
Expression of a drug and xenobiotic metabolizing enzymes, cytochrome P450s (CYPs), and antioxidant enzymes can be modulated by various factors. The flavonoid rutin was investigated for its anti-carcinogen and protective effects as well as modulatory action on CYPs and phase II enzymes in human hepatocellular carcinoma cells. Rutin inhibited proliferation of HEPG2 cells in a dose-dependent manner with the IC50 value of 52.7 μmol L-1 and invasion of HEPG2 cells (21.6 %, p = 0.0018) and colony formation of those invaded cells (57...
December 1, 2016: Acta Pharmaceutica
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