Glutatione S-transferase Research Articles

Influence of Prematurity and Glutation S-Transferase Gene Polymorphisms on the Degree of Asthma Control in Children

Influence of Prematurity and Glutation S-Transferase Gene Polymorphisms on the Degree of Asthma Control in Children

Derivatives of 3-Hydroxypyridine in The Correction of Disorders in The Structural and Functional Properties of Erythrocytes in Experimental Acute Destructive Pancreatitis Due to Chronic Ethanol Intoxication

At present, acute pancreatitis only in some areas is a rather well-studied disease of the abdominal organs, however, the destructive forms of this disease have various developmental patterns, complications and, often unfavorable outcomes. The aim of the research is to establish the possibilities to correct the disorders in the functional and structural features of erythrocytes by 3-hydroxypyridine derivatives in experimental acute destructive pancreatitis due to chronic ethanol intoxication. In experimental acute destructive pancreatitis due to a 60-day ethanol intoxication there was a decrease in the content of proteins (a - ? ß -spectrin, ankyrin, anion transport protein, actin, gyceraldehyde-3-phosphate dehydrogenase, glutation-S transferase) and lipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, glycerophospholipids, sphingomyelin, phospholipids, triacylglycerol, sum of mono- and diacylglycerol), an elevated level of band 4.1 and 4.5 proteins, pallidin, dematin, tropomyosin and lipids (lysophosphatidylcholine, cholesterol, it’s esters, non-esterified fatty acids), a disorder in intrinsic cellular metabolism of erythrocytes (an increased concentration of lipid peroxidation products, a decreased activity of catalase, superoxide dismutase, degree of stable metabolites of nitrogen oxide and sorption indicators of membrane) in the erythrocyte membrane. The study has revealed that the greatest efficiency in correction of disorders in the functional and structural feutures of erythrocytes from among the derivatives of 3-hydroxypyridine has a compound ß - hydroxynicotinoylhydrazon 2-methyl-3-hydroxy-4-formyl-5-oxymethylpyrydine dihydrochloride, and the least one - 2-ethyl-6- methyl-3-hydroxypyrydine malate (etoxydol), the administration of 2-ethyl-6-methyl-3-hydroxypyrydine succinate (mexidol) has shown an intermediate result.

Evaluation of Some Phenolic Compounds as Inhibitors of Glutatione S-Transferase Enzyme

Glutatyon S-transferazlar (GSTs) önemli antioksidan enzim sınıfındadırlar ve glutatyonun toksik metabolitlerle konjugasyonunu katalize ederler. Yapılan bu çalışmada, bazı fenolik bileşiklerin GST enziminin aktivitesi üzerine potansiyel inhibisyon etkileri in vitro olarak test edilmiştir. Morin hidrat, eskuletin hidrat, p-kumarik asit ve siringaldehit fenolik bileşiklerinin GST enzimi üzerine IC50 değerleri sırasıyla 0.718 μM, 0.713 μM, 0.701 μM ve 0.699 μM olarak bulunmuştur. Ki değerleri ise sırasıyla 1.610±0.120, 0.179± 0.019, 4.590±0.480, 0.999±0.070 olarak bulunmuştur. Bu sonuçlara göre en iyi inhibisyon etkisini eskuletin hidrat göstermiş olup yarışmalı inhibisyon türü sergilemiştir.

Multibiomarker responses after exposure to a sublethal concentration of thiamethoxam in the African honeybee (Apis mellifera intermissa)

Thiamethoxam is an insecticide mainly used in agriculture to control insect pests. However, non-target insect species, such as honeybees, may also be impacted. In this study, adults of Apis mellifera intermissa were orally exposed under laboratory conditions to a sublethal concentration of thiamethoxam (CL25= 0.17 ng/μl) for 9 days and the effects were evaluated at the biochemical level, by monitoring specific oxidative stress and neuronal biomarkers. Results showed an increase in the antioxidant enzymes, glutatione-S-transferase (GST), catalase (CAT) and glutathione peroxidase (GPx) and in content of malondialdehyde (MDA).The activity of acetylcholinesterase (AChE) was downregulated as evidence of a neurotoxic action and no significant change was observed in glutathione (GSH). Exposure to the insecticide thiamethoxam induced oxidative stress and defense mechanisms affecting honeybee physiology.

Resistance of Nilaparvata lugens to Fenobucarb and Imidacloprid and Susceptibility to Neem Oil Insecticides

This study aims to monitor and determine the level of resistance of N. lugens to fenobucarb and imidacloprid, to analyse of the specific activities of asetylcholinesterase, Glutation S-Transferase, esterase, and to determine sensitivity of resistant N. lugens to the neem oil. Resistance tests were conducted on a field population from Cipunagara, Subang, West Java, Indonesia, and a standard population originating from Banyuwangi, East Java, that was obtained from the Indonesian Center for Rice Research. Synthetic and neem Insecticides were applied using the leaf-stem dipping method. The resistance ratio obtained by comparing the LC50 value of the field population with the standard. The test insects were considered to be resistant to synthetic insecticide if they had a resistance ratio (RR) of more than 4, indicated resistance if RR ≥1, and susceptible to neem if has RR <1. The results of the research showed that the N. lugens population of Cipunagara indicated resistance to fenobucarb (RR = 2.43), while it was clearly resistance to imidacloprid (RR = 13.95). Specific activities of the acetylcholinesterase and Glutathione S-Transferase of the N. lugens Cipunagara populations were higher than the standard, while the esterase specific activity was lower. These two enzymes are responsible for the resistance of N. lugens to fenobucarb and imidacloprid. Nevertheless, the N. lugens population of Cipunagara was susceptible to neem (RR <1) that never been reported before. Therefore, it is important to know the change in the sensitivity of the target and the metabolic pathway of the insecticide used to manage insect resistance.

Differential modulation of oxidative stress, antioxidant defense, histomorphology, ion-regulation and growth marker gene expression in goldfish (Carassius auratus) following exposure to different dose of virgin microplastics

Goldfish (Carassius auratus) juveniles were exposed to virgin polyvinyl chloride microplastics (PVC-MPs) in triplicate at 0, 0.1 or 0.5 mg/L for four days. Afterwards, the histopathology of the gills, liver and intestines were examined, along with various antioxidant enzymes and indicators of oxidative damage (malondialdehyde (MDA) and hydrogen peroxide (H2O2)), in the brain, liver and gills. In addition, we also studied the expression of hepatic insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 1 (IGFBP-1) and growth hormone (GH) receptor, while cortisol receptor (CR) and cytochrome P450 1A (CYP1A) gene expression were assayed in both the liver and gills. Histological analysis revealed PVC-MPs in the intestines at 0.1 and 0.5 mg/L, along with substantially shorter villi. The gills appeared undamaged by PVC-MPs exposure and had limited or no effect to antioxidant activity, Na+/K+-ATPase and H+-ATPase activity or plasma ion levels, but there was a prominent upsurge of the detoxification enzymes glutatione S-transferase (GST) activity and CYP1A expression. Livers showed inflammation and some occurrences of hemorrhaging and necrosis at 0.5 mg/L. While the brain showed some evidence of oxidative damage, the liver was the most susceptible to oxidative damage, based on increased MDA, H2O2 and various antioxidant enzymes. Hepatic expression of IGFBP-1 and GH receptor were significantly downregulated at 0.5 mg/L while CR was upregulated. Results indicate that exposure to environmentally relevant PVC-MP can cause oxidative damage in the brain and liver, adverse histomorphological changes to the intestine and liver and alter the gene expression in goldfish.

Steroid androgen 17 alpha methyltestosterone used in fish farming induces biochemical alterations in zebrafish adults

The 17 alpha methyltestosterone (MT) hormone is fed to Oreochromis niloticus larvae in fish farms with the purpose of inducing sex reversal. The aim of this study was to evaluate the toxicity and sub-lethality of MT (99.9% purity) and cMT (a commercial MT with 90% purity) in zebrafish (Danio rerio) adults, where the animals were exposed to concentrations of 0, 4, 23, 139, 833 and 5000 µg/L for 96 hours. Genotoxicity was evaluated by micronucleus test (MN), nuclear abnormalities (NA) and comet assay. A low genotoxic potential of MT was showed, inducing micronucleus, nuclear abnormalities and DNA damage in Danio rerio, depending on the use of MT or cMT, gender and tested concentrations. In the sub-lethality trials, there was a basal difference in the activity of the enzymatic biochemical markers for males and females, while the Glutatione S transferase (GST) activity decreased in all analyzed tissues, and for males the enzymatic activity decreased only in the intestine. Results suggest that MT has a toxic potential to fish because it alters enzymatic metabolic pathways and may pose a risk to the ecosystems.

Pengaruh Pemberian Ekstrak Umbi Bawang Dayak (Eleutherine palmifolia L. Merr.) Terhadap Kadar Mda (Malondialdehid) Serum Tikus Putih (Rattus norvegicus) Jantan Galur Wistar Yang Diinduksi Parasetamol

<h2>ABSTRACT</h2><p><strong>Background:</strong> Paracetamol induced hepatotoxic effect because paracetamol increased production of N-acetyl-para-benzoquinone imine (NAPQI). Dayak onion contains flavonoids that inhibits cytochrome P450 activity, increases Glutation S-transferase (GST) activity, and scavenges free radicals.</p><p><strong>Method</strong><strong>: </strong>This study used 24 male wistar rats (<em>Rattus norvegicus</em>) divided into 3 groups: group of rats without paracetamol induction, group of rats induced by 1750mg/kgBW paracetamol on 14th day, and group of rats given 300mg/kgBW dayak onion bulb extract (<em>Eleutherine palmifolia</em> L. Merr) for 14 days and induced by 1750 mg/kgBW paracetamol on 14th day. <strong></strong></p><p><strong>Result</strong><strong>: </strong>The result of One Way Anova showed that serum malondialdehyde level of group of rats induced by paracetamol ( =129,063±42,0497mg/dl) was significantly higher (p=0.006) than group of rats without paracetamol induction ( =85,688±15,9976mg/dl). Serum malondialdehyde (MDA) level of group of rats given dayak onion bulb extract induced by paracetamol ( =118,500±19,4054mg/dl) was not significantly lower (p=0,463) than group of rats induced by paracetamol ( =129,063±42,0497mg/dl).</p><p><strong>Conclusion:</strong> The conclusion of this study showed that paracetamol significantly increased serum malondialdehyde (MDA) level and dayak onion bulb extract was not significantly decreased serum malondialdehyde (MDA) level.</p><p><strong>Keywords: </strong><em>Eleutherine palmifolia</em> L. Merr, malondialdehyde, paracetamol</p>

C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?

To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase(TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.

INSULINA ESTIMULA LA PROLIFERACIÓN CELULAR DEPENDIENTE DE AUXINAS EN LOS CULTIVOS DE CÉLULAS EN SUSPENSIÓN DE TABACO NT-1

La insulina regula el crecimiento en plantas como maíz y frijol, a través de la proliferación celular. En este estudio observamos que en cultivos de tabaco NT-1, la hormona regula la proliferación celular de manera dependiente de la presencia de auxinas. Los cultivos donde se limitó la concentración de auxinas, presentaron una baja actividad mitótica, la cual fue re establecida por la adición de 1.23 nM de insulina a través de la expresión de los genes ciclina B, CDKB, E2F, subunidad β- de la proteína G ARC A y glutation-S-transferasa (GST). Los cultivos también presentaron un incremento en peso seco y células pequeñas que corresponden a un fenotipo con alta división celular. Por otra parte, se ha reportado que la ausencia de auxinas en este tipo de cultivos de células de tabaco en suspensión conduce a una sincronización parcial, y en este sistema la insulina también promovió la proliferación, incrementando la expresión del gen E2F.

New hits as phase II enzymes inducers from a focused library with heteroatom-heteroatom and Michael-acceptor motives.

The increased activity of phase-II-detoxification enzymes, such as quinone reductase (QR) and glutation S-transferase (GST), correlates with protection against chemically induced carcinogenesis. Herein we studied 11 different chemotypes, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiazole, 1,3,4-oxathiazole, thienyl hydrazone, α,β-unsaturated-oxime, α,β-unsaturated-N-oxide, coumarin and α,β-unsaturated-carbonyl, as phase-II enzymes inducers in order to identify new pharmacophores with chemopreventive activity. Fifty-four compounds were analyzed on wild-type mouse-hepatoma Hepa-1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BpRc1 cells. New monofunctional inducers of QR and GST were identified, the 1,2,5-oxadiazol-2-oxide (3), the 1,2,4-triazine-4-oxides (23) and (32) and the tetrahydropyrimidinones (28) and (49). It was confirmed that Nrf2 nuclear translocation is the operative molecular mechanism that allows compound (3) to exert protective effects via expression of downstream phase-II enzymes.

Status dan Mekanisme Resistensi Biokimia Crocidolomia pavonana (F.) (Lepidoptera: Crambidae) terhadap Insektisida Organofosfat serta Kepekaannya terhadap Insektisida Botani Ekstrak Biji Barringtonia asiatica

An examination of insect resistance was determined by several steps, i.e. standard sensitivity, resistance diagnosis, and determination of resistance level. Each phase was tested with feeding and residue contact methods at glass tube. Resistance ratio (RR) was determined by comparing LC50 value of field population with standard population. Field population of C. pavonana was classified resistant if it had RR 5 4. Biochemistry analysis of resistance was conducted to population of C. pavonana showing resistance to prophenophos insecticide. The activity analysis of acetylcholine esterase (ACHE), esterase, and Glutation Stransferase was done with spectrophotometer method. Insect which are resistant to prophenophos insecticide was tested for its sensitivity to Barringtonia asiatica seed extract. Result indicated that C. pavonana population from Pengalengan showed resistance to prophenophos synthetic insecticide. Using contact test, the highest resistance ratio value was 4.04, while by feeding assay the RR was 2.78. The study on biochemical resistance mechanisms of each field population of C. pavonana showed various activities of enzymatic detoxification. This could be due to the difference in the kind of insecticides exposed to each field population of C. pavonana. Since RR value from the contact test was higher than that of the feeding test, the resistance development of C. pavonana to synthetic insecticides was probably caused by physiological and biochemical changes in insect cuticle rather than the activity of detoxification enzyme. Methanolic seed extract of B. asiatica can be used as an alternative of resistance management of C. pavonana to prophenophos synthetic insecticide.

An in vivo evaluation of acute toxicity of cobalt ferrite (CoFe2O4) nanoparticles in larval-embryo Zebrafish (Danio rerio)

The broad spectrum applications of CoFe2O4 NPs have attracted much interest in medicine, environment and industry, resulting in exceedingly higher exposures to humans and environmental systems in succeeding days. Their health effects and potential biological impacts need to be determined for risk assessment. Zebrafish (Danio rerio) embryos were exposed to environmentally relevant doses of nano-CoFe2O4 (mean diameter of 40nm) with a concentration range of 10–500μM for 96h. Acute toxic end points were evaluated by survival rate, malformation, hatching delay, heart dysfunction and tail flexure of larvae. Dose and time dependent developmental toxicity with severe cardiac edema, down regulation of metabolism, hatching delay and tail/spinal cord flexure and apoptosis was observed. The biochemical changes were evaluated by ROS, Catalase (CAT), Lipid peroxidation (LPO), Acid phophatase (AP) and Glutatione s- transferase (GST). An Agglomeration of NPs and dissolution of ions induces severe mechanical damage to membranes and oxidative stress. Severe apoptosis of cells in the head, heart and tail region with inhibition of catalase confirms ROS induced acute toxicity with increasing concentration. Increased activity of GST and AP at lower concentrations of CoFe2O4 NPs demonstrates the severe oxidative stress. Circular dichroism (CD) spectra indicated the weak interactions of NPs with BSA and slight changes in α-helix structure. In addition, CoFe2O4 NPs at lower concentrations do not show any considerable interference with assay components and analytical instruments. The results are possible elucidation of pathways of toxicity induced by these particles, as well as contributing in defining the protocols for risk assessment of these nanoparticles.

Searching phase II enzymes inducers, from Michael acceptor-[1,2]dithiolethione hybrids, as cancer chemopreventive agents.

Cancer chemoprevention involves the carcinogenic process prevention, delay or reverse by the administration of chemopreventive agents, which are able to suppress or block the carcinogen metabolic activation/formation. The increased activity of phase II detoxification enzymes such as quinone-reductase (QR) and glutation-S-transferase (GST) correlates with the protection against chemically-induced carcinogenesis. It has been shown that synthetic chalcones and 3H-[1,2]-dithiole-3-thiones promote expression of genes involved in chemoprevention. Herein, the induction of phase II enzymes by designed Michael acceptor-dithiolethione hybrids was studied. Hybrids 5 and 7 displayed the induction of quinone-reductase and glutation-S-transferase in vitro in the same order on the wild-type mouse-hepatoma Hepa 1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BPrc1 cells indicating that 7 displays the best chemopreventive potential.

Mycobacterium tuberculosis EspB protein suppresses interferon-γ-induced autophagy in murine macrophages.

Mycobacterium tuberculosis (Mtb) persists within immature phagosomes by preventing their maturation into phagolysosomes. Although the early secretory antigenic target 6 (ESAT-6) system 1 (ESX-1) secretion-associated protein B (EspB) of Mtb is strongly linked to immunogenicity and virulence of this organism, its mechanism of action remains largely unclear. This study aimed to investigate EspB effects on autophagy in murine ANA-1 macrophage cells. EspB gene was amplified by polymerase chain reaction from Mtb H37Rv genomic DNA to express recombinant EspB protein. Levels of autophagic markers, including Microtubule-associated protein 1 light chain 3 beta (LC3B-I and -II), phosphorylated signal transducer and activator of transcription (STAT)1 and total STAT1 in ANA-1 cells treated with EspB proteins were assessed by Western blotting. In addition, autophagic vacuoles were detected by fluorescence microscopy. Finally, IFN-γR1 expression was evaluated by semiquantitative reverse transcriptase polymerase chain reaction and flow cytometry. EspB gene was expressed in Escherichia coli cells to yield a soluble N-terminal glutatione S-transferase tag fusion protein used in subsequent experiments. Preincubation with EspB significantly suppressed autophagosome formation and LC3B expression induced by interferon (IFN)-γ stimulation, in a dose-dependent manner. These results were confirmed by the reduced incorporation of monodansylcadaverine, a marker for the acidic compartment of autolysosomes, after treatment with EspB. Interestingly, we found that IFN-γ receptor 1 mRNA and protein levels were decreased in EspB-stimulated ANA-1 cells in comparison with untreated cells. Finally, EspB protein also inhibited IFN-γ-activated STAT1 phosphorylation, thereby downmodulating macrophage responsiveness to IFN-γ. EspB inhibits autophagosome formation in murine macrophages, at least in part by downregulating IFN-γ receptor 1 expression. Overall, EspB should be considered a relevant factor in the pathogenesis of mycobacterial infections in humans.

Probable effects of glutatione s-transferase p1 gene exon-6 (ala114val) polimorphism on the etiology of lung cancer

Objectives: Genetic susceptibility also has significant effects on the etiology of lung cancer, besides smoking. Previously it has been reported that some genetic polymorphisms have important roles; especially Glutatyon S-Transferaz P1 (GSTP1) gene for the development of lung cancer. GSTP1 gene has a role in phase II of xenobiotic metabolism. GSTP1 Exon-6 polymorphisms have functional effects on gene production and causes differences in enzyme activity.The aim of this study was to investigate probable effects of GSTP1gene exon-6 (ala114val) polimorphism on the etiology of lung cancer. Materials and methods: Our research population consistsed of 160 subjects; 80 as control group and 80 suffering from lung cancer. Genomic DNA was extracted from peripheral blood leukocytes and the genotypes have been determined by using PCR and RFLP methods. Results: No effect of exon 6 (ala114val) polymorphism genotype of GSTP1 gene were found on etiology of lung cancer in present study. This study showed that smoking, old age and being male are important risk factors for lung cancer. Additionally, our sample\'s GSTP1 gene exon 6 (ala114val) polymorphism genotype frequencies were determined. Conclusions: Our data derived from present study did not suggest an effect of GSTP1gene exon-6 (ala114val) polimorphism on the etiology of lung cancer.

Changes in lipid transport-involved proteins of epicardial adipose tissue associated with coronary artery disease

ObjectiveRecent studies have focused on the potential role of epicardial adipose tissue (EAT) in the physiopathology of several metabolic and cardiovascular diseases, especially coronary artery disease (CAD). We aimed to study whether there are differences in the proteome and the secretome between epicardial and subcutaneous adipose tissue (SAT) from patients with and without CAD. MethodsEAT and SAT samples were collected from 64 patients undergoing elective cardiac surgery either for coronary artery bypass grafting or valve surgery. One or two-dimensional electrophoresis were performed on tissue samples and media collected at 3, 6, 24 or 48 of tissue culture. Protein identification was performed with mass spectrometry, and the results were then validated with Western blot or enzyme immunoassay. mRNA expression levels were analysed by real time polymerase chain reaction. ResultsThe release of several proteins was found to be higher in EAT that in SAT. Remarkably, there were higher levels of apolipoprotein A-I and glutation S-transferase P release, whereas mRNA expression of fatty acid binding protein 4 was lower in EAT. Although apolipoprotein A-I protein quantity in EAT was similar between CAD and non CAD patients, its released levels from this fat pad were lower in CAD. ConclusionEAT and SAT show different profiles of protein release and a different pattern was also found in samples from patients with CAD. These findings might support the hypothesis that EAT plays an interesting role in the physiopathology of atherosclerosis and CAD.

Evaluation of methylation status in glutation S- transferase P1(GSTP1) gene promoter in human breast cancer and its relation to tumor grade and stage

Glutation S-transferase P1 (GSTP1) gene methylation in promoter CpG islands has been described as a specific biomarker for many types of cancer including breast cancer as a tumor suppressor gene. At the present study we found that the GSTP1 gene promoter to be methylated in breast cancer tissues. For studying the difference of sequence in hypermethylated GSTP1 promoter in cancer tissues and non methylated status in normal tissues, we analyzed the cytosine methylation status as epigenetic changes in 50 tumors from patients with breast cancer and 50 normal breast tissues that were obtained from the adjacent regions of the breast tumors of the same patients. In order to study the promoter methylation status for GSTP1 gene in breast cancer, 40 CpG sites [nucleotide(nt) 197, 190, 187, 185, 183, 182, 176, 162, 155, 152, 148, 145, 141, 132, 127, 124, 112, 109, 101, 99, 81, 77, 74, 71, 54, 53, 48, 47, 43, 42, 40, 38, 23, 22, 15, 14, 13, 11, 8, 4] were screened. The GSTP1 methylation was detected in 41.3% of the breast tumors which was associated with higher tumor grade (p=0.467) and tumor stage (p = 0.048). Key words: GSTP1, promoter, methylation, pattern, breast cancer.

Evaluation of methylation status in glutation S-transferase P1(GSTP1) gene promoter in human breast cancer and its relation to tumor grade and stage

Glutation S-transferase P1 (GSTP1) gene methylation in promoter CpG islands has been described as a specific biomarker for many types of cancer including breast cancer as a tumor suppressor gene. At the present study we found that the GSTP1 gene promoter to be methylated in breast cancer tissues. For studying the difference of sequence in hypermethylated GSTP1 promoter in cancer tissues and non methylated status in normal tissues, we analyzed the cytosine methylation status as epigenetic changes in 50 tumors from patients with breast cancer and 50 normal breast tissues that were obtained from the adjacent regions of the breast tumors of the same patients. In order to study the promoter methylation status for GSTP1 gene in breast cancer, 40 CpG sites [nucleotide(nt) 197, 190, 187, 185, 183, 182, 176, 162, 155, 152, 148, 145, 141, 132, 127, 124, 112, 109, 101, 99, 81, 77, 74, 71, 54, 53, 48, 47, 43, 42, 40, 38, 23, 22, 15, 14, 13, 11, 8, 4] were screened. The GSTP1 methylation was detected in 41.3% of the breast tumors which was associated with higher tumor grade (p=0.467) and tumor stage (p = 0.048). Key words: GSTP1, promoter, methylation, pattern, breast cancer.

Differential proteomic analysis of highly purified placental cytotrophoblasts in pre‐eclampsia demonstrates a state of increased oxidative stress and reduced cytotrophoblast antioxidant defense

Proteomics were performed using highly (99.99%) purified cytotrophoblasts from six normal and six pre-eclamptic placentas. Eleven proteins were found which decreased in pre-eclampsia (actin, glutathione S-transferase, peroxiredoxin 6, aldose reductase, heat shock protein 60 (Hsp60), two molecular forms of heat shock protein 70 (Hsp70) β-tubulin, subunit proteasome, ezrin, protein disulfide isomerase, and phosphoglycerate mutase 1). Only one protein, α-2-HS-glycoprotein (fetuin), was found to increase its expression. Western blots of actin, Hsp70, ezrin, and glutatione S-transferase confirmed decrease in protein expression. Many of the proteins that decreased are consistent with a state of oxidative stress in the pre-eclamptic placenta and a decreased cytotrophoblast defense against and response to oxidative stress.