Glutathione S-transferase Family Research Articles

Glycyrrhizic acid ameliorates hepatic fibrosis by inhibiting oxidative stress via AKR7A2

BackgroundHepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear. PurposeTo investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs. MethodsA mouse model of hepatic fibrosis was prepared with 20% carbon tetrachloride (CCl4) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays. ResultsIn vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl4-treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments. ConclusionGA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic fibrosis.

Modulation of Cardiac Ryanodine Receptors by Chloride Intracellular Ion Channel 2

Pathogenic variants of the Chloride intracellular ion channel 2 (CLIC2) are implicated in hypertrophic cardiomyopathy (HCM), a diverse heart condition leading to arrhythmic sudden cardiac death and heart failure. CLIC2 is a unique class of metamorphic protein, related to the enzymatic glutathione s-transferase family and form functional ion channel. Artificial bilayer studies have shown that CLIC2 negatively modulates the activity of cardiac ryanodine receptor 2 (RyR2), implicating the sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ release. However, the subsequent consequences of RyR2 and CLIC2 interaction in cardiac physiology remains unknown. Therefore, we ablated clic2 in human induced pluripotent stem cell (hiPSC) line using the CRISPR-Cas9 system and performed cardiomyocyte differentiation. clic2−/− hiPSC-derived cardiomyocytes (hiPSC-CMs) showed altered electrophysiological properties leading to impaired excitation-contraction coupling. clic2−/− hiPSC-CMs showed an increase in beat rate and field potential duration by 143.49±5.96% and 162.43±5.82%, respectively, whereas conduction velocity and spike amplitude decreased by 43.81±2.22% and 43.32±3.54%, respectively compared to WT hiPSC-CMs. Additionally, action potential duration measurements of clic2−/− hiPSC-CMs showed a decrease in APD30, APD50, and APD90 by 74.42%, 65.19%, and 66.46%, respectively compared to WT hiPSC-CMs. Moreover, clic2−/− hiPSC-CMs showed altered Ca2+ handling, with a decrease in peak amplitude (57.07±2.25%) and duration (38.29±1.30%) compared to the WT hiPSC-CMs. The caffeine induced Ca2+ release in clic2−/− hiPSC-CMs, attributed to the SR/ER Ca2+ overload which decreased by 72.19±3.51% compared to WT hiPSC-CMs. Transcriptomics analysis of clic2−/− hiPSC-CMs revealed 223 transcripts with significant changes in expression levels (89 upregulated and 134 downregulated), implicating CLIC2 in hypertrophy cardiomyopathy, dilated cardiomyopathy, and other heart diseases. Furthermore, the protein expression of CLIC2 increases in end-stage failing human heart samples compared to the non-failing heart. In conclusion, our study sheds light on the novel role of CLIC2 in the regulation of cardiac (patho)physiology. National Institutes of Health (NIH) (HL133050, and HL157453); American Heart Association-Transformational Project Award; National Center for advancing translational sciences (TR004178, understudied proteins and druggable targets) (HS). Presidential Predoctoral Fellowship; Margaret T. Nishikawara Merit Scholarship Endowment in Physiology; Graduate School’s Alumni Grants for Graduate Research and Scholarship Program, The Ohio State University (SS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In silico identification and expression analysis of glutathione S‐transferase in Tenebrio molitor

AbstractSelective herbicides are used to control undesirable vegetation or weeds in fields without harming crops. Herbicide use for weed management can directly impact the densities of insect pests in agricultural communities as a result of insect mortality during and immediately after application. In insects, the glutathione S‐transferase (GST) enzyme is involved in both the detoxification process and the defense of cellular membranes against oxidative damage. In this study, two TmGSTs (TmGST‐iso1 and TmGST‐iso2) were identified and characterized to elucidate the GST family in Tenebrio molitor. Among the developmental stages of T. molitor, eggs had the highest expression levels of TmGST‐iso1. TmGST‐iso2 expression was highest in the pre‐pupal stage. TmGST‐iso1 expression was high in the guts of early and late larvae, whereas TmGST‐iso2 expression was not observed in early larvae. Adults, both male and female, had the highest levels of TmGST‐iso1 mRNA expression in the gut and reproductive organs, and the highest levels of TmGST‐iso2 expression in the reproductive organs. Quantitative polymerase chain reaction was used to investigate the impact of treatment with butachlor on the mRNA expression of TmGST‐iso1 and TmGST‐iso2 in larvae. TmGST‐iso1 expression increased in the butachlor‐treated group after 3 and 24 h, whereas TmGST‐iso2 expression peaked at 24 h after treatment. This study provides vital information about the detoxifying activities of T. molitor.

Transcriptomic Association Analysis of the Metabolic Mechanism of Sulfamethoxazole in Channel Catfish (Ictalurus punctatus).

Sulfamethoxazole is a widely used antimicrobial drug used to treat bacterial diseases in aquaculture. To understand the gene expression in channel catfish liver after treatment with sulfamethoxazole, in this study, the treatment group received sulfamethoxazole (100 mg/kg bw), which was administered orally once, and samples were taken at 5 h, 12 h, and 6 d after the administration of sulfamethoxazole, while the control group was orally administered sterile water. To further identify potentially significant genes, a transcriptome analysis using RNA-seq was carried out. More than 50 million high-quality reads were found. After filtering and quality analysis, these reads were identified as 54,169,682, 51,313,865, 51,608,845, and 49,333,491. After counting 23,707 of these transcripts for gene expression, it was discovered that 14,732 of them had genes with differential expression. Moreover, we found that the annotation with the most GO variation was "cellular process" (1616 genes), "metabolic process" (1268 genes), "binding" (1889 genes), and "catalytic activity" (1129 genes). KEGG pathways showed that the "metabolic pathway" was the pathway that was significantly enriched in both experimental groups when comparing the experimental groups: 5 h and 12 h (128 genes); 5 h and 6 d (332 genes); and 12 h and 6 d (348 genes). Also, UDP- glucuronosyltransferase (ugt), which is associated with glucuronidation, and UDP-glucuronosyltransferase 2C1-like (ugt2a1) showed significant upregulation. Carboxylesterase 5A-like (ces3), which promotes fatty acyl and cholesteryl ester metabolism, and the glutathione transferase family were upregulated in the expression of sulfamethoxazole metabolism in the liver, which significantly affected the metabolic effects of the drug. Meanwhile, dypd, uck2b, and rrm2, which are related to nucleotide synthesis and metabolism, were upregulated. Our study extends the knowledge of gene expression in drug metabolism in channel catfish and further provides insight into the molecular mechanism of sulfamethoxazole metabolism.

The potential influence of GSTT1 null genetic polymorphism on coronary artery disease: A pilot study in a South Indian cohort

BackgroundIndians are known to have the highest rates of coronary artery disease (CAD), with the conventional risk factors failing to explain the increased risk. Possible candidate genes to study both the environmental and genetic risk associated with CAD is the glutathione S-transferase (GST) family, as it is involved in detoxification. MethodsThis case–control assessed the association between GSTM1 and GSTT1 polymorphisms in Indian patients with CAD. Fifty patients with CAD and 50 healthy volunteers were genotyped for the two polymorphisms by polymerase chain reaction. The genotype frequencies between the groups were compared, where a p-value of less than 0.05 was considered as statistically significant. ResultsThere was a significant inverse association between GSTT1 null polymorphism and CAD susceptibility.

Enzymatic Degradation of Deoxynivalenol with the Engineered Detoxification Enzyme Fhb7.

In the era of global climate change, the increasingly severe Fusarium head blight (FHB) and deoxynivalenol (DON) contamination have caused economic losses and brought food and feed safety concerns. Recently, an FHB resistance gene Fhb7 coding a glutathione-S transferase (GST) to degrade DON by opening the critical toxic epoxide moiety was identified and opened a new window for wheat breeding and DON detoxification. However, the poor stability of Fhb7 and the elusiveness of the catalytic mechanism hinder its practical application. Herein, we report the first structure of Fhb7 at 2.41 Å and reveal a unique catalytic mechanism of epoxide opening transformation in GST family proteins. Furthermore, variants V29P and M10 showed that 5.5-fold and 266.7-fold longer half-life time than wild-type, respectively, were identified. These variants offer broad substrate scope, and the engineered biosafe Bacillus subtilis overexpressing the variants shows excellent DON degradation performance, exhibiting potential at bacterium engineering to achieve DON detoxification in the feed and biomedicine industry. This work provides a profound mechanistic insight into the enzymatic activities of Fhb7 and paves the way for further utilizing Fhb7-related enzymes in crop breeding and DON detoxification by synthetic biology.

Auxin-responsive ROS homeostasis genes display dynamic expression pattern during rice crown root primordia morphogenesis

Reactive oxygen species (ROS) are generated continuously as a by-product of aerobic metabolism in plants. While excessive ROS cause oxidative stresses in cells, they act as signaling molecules when maintained at an optimum concentration through the dynamic equilibrium of ROS metabolizing mechanisms to regulate growth, development and response to environmental stress. Auxin and its crosstalk with other signaling cascades are crucial for maintaining ROS homeostasis and orchestrating root architecture but dissecting the underlying mechanism requires detailed investigation at the molecular level. Rice fibrous root system is primarily composed of shoot-derived adventitious roots (also called crown roots). Here, we uncover auxin-ROS cross-talk during initiation and growth of rice roots. Potassium iodide treatment changes ROS levels that results in an altered rice root architecture. We reveal that auxin induction recover root growth and development defects by recouping level of hydrogen peroxide. By comparing global datasets previously generated by auxin induction and laser capture microdissection-RNA sequencing, we identify the redox-related antioxidants genes from peroxidase, glutathione reductase, glutathione S-transferase, and thioredoxin reductase families whose expression is regulated by the auxin signaling and also display dynamic expression patterns during crown root primordia morphogenesis. The auxin-mediated differential transcriptome data were validated by quantifying expression levels of a set of genes upon auxin induction. Further, in-depth spatio-temporal expression pattern analysis by RNA in situ hybridization shows the spatially restricted expression of selected genes in the developing crown root primordia. Together, our findings uncover molecular components of auxin-ROS crosstalk involved in root organogenesis.

GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes

BackgroundHeart failure (HF) seriously threatens human health worldwide. However, the pathological mechanisms underlying HF are still not fully clear.ResultsIn this study, we performed proteomics and transcriptomics analyses on samples from human HF patients and healthy donors to obtain an overview of the detailed changes in protein and mRNA expression that occur during HF. We found substantial differences in protein expression changes between the atria and ventricles of myocardial tissues from patients with HF. Interestingly, the metabolic state of ventricular tissues was altered in HF samples, and inflammatory pathways were activated in atrial tissues. Through analysis of differentially expressed genes in HF samples, we found that several glutathione S-transferase (GST) family members, especially glutathione S-transferase M2-2 (GSTM2), were decreased in all the ventricular samples. Furthermore, GSTM2 overexpression effectively relieved the progression of cardiac hypertrophy in a transverse aortic constriction (TAC) surgery-induced HF mouse model. Moreover, we found that GSTM2 attenuated DNA damage and extrachromosomal circular DNA (eccDNA) production in cardiomyocytes, thereby ameliorating interferon-I-stimulated macrophage inflammation in heart tissues.ConclusionsOur study establishes a proteomic and transcriptomic map of human HF tissues, highlights the functional importance of GSTM2 in HF progression, and provides a novel therapeutic target for HF.

First Report on Resistance to HPPD Herbicides Mediated by Nontarget-Site Mechanisms in the Grass Leptochloa chinensis.

The emergence of 4-hydroxyphenylpyruvate dioxygenase (HPPD) herbicides as efficacious target-site herbicides has been noteworthy. In recent years, only four species of broadleaf weeds have developed resistance due to the long-term widespread use of HPPD herbicides. This study represents the first reported instance of a grass weed exhibiting resistance to HPPD inhibitors. We identified a new HPPD-resistant Chinese sprangletop [Leptochloa chinensis (L.) Nees] population (R population). At the recommended dose of tripyrasulfone, the inhibition rate of the R population was only half that of the sensitive population (S). The mechanism underlying resistance does not involve target-site resistance triggered by amino acid mutations or depend on disparities within the HPPD INHIBITOR SENSITIVE 1 (HIS1) gene. The impetus for resistance appears to be interlinked with the metabolic activities of cytochrome P450 monooxygenase (P450) and glutathione S-transferase (GST) family genes. Following RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) validation, the study suggests that five P450 genes, CYP71C1, CYP74A2, CYP72A1, CYP84A1, and CYP714C2, alongside a single GST gene GSTF1, may be implicated in the process of metabolic detoxification.

Genome-Wide Scanning Loci and Differentially Expressed Gene Analysis Unveils the Molecular Mechanism of Chlorantraniliprole Resistance in Spodoptera frugiperda.

Chlorantraniliprole has been widely used to controlSpodoptera frugiperda, but it has led to the development of chlorantraniliprole resistance. Multiomics analysis of strains with two extreme traits helps to elucidate the complex mechanisms involved. Herein, following genome resequencing and application of the Euclidean distance algorithm, 550 genes within a 16.20-Mb-linked region were identified from chlorantraniliprole-resistant (Ch-R) and chlorantraniliprole-susceptible (Ch-Sus) strains. Using transcriptome sequencing, 2066 differentially expressed genes were identified between Ch-R and Ch-Sus strains. Through association analysis, three glutathione S-transferase family genes and four trehalose transporter genes were selected for functional verification. Notably, SfGSTD1 had the strongest binding ability with chlorantraniliprole and is responsible for chlorantraniliprole tolerance. The Ch-R strain also increased the intracellular trehalose content by upregulating the transcription of SfTret1, thereby contributing to chlorantraniliprole resistance. These findings provide a new perspective to reveal the mechanism of resistance of agricultural pests to insecticides.

The Multifaceted Role of Glutathione S-Transferases in Health and Disease.

In humans, the cytosolic glutathione S-transferase (GST) family of proteins is encoded by 16 genes presented in seven different classes. GSTs exhibit remarkable structural similarity with some overlapping functionalities. As a primary function, GSTs play a putative role in Phase II metabolism by protecting living cells against a wide variety of toxic molecules by conjugating them with the tripeptide glutathione. This conjugation reaction is extended to forming redox sensitive post-translational modifications on proteins: S-glutathionylation. Apart from these catalytic functions, specific GSTs are involved in the regulation of stress-induced signaling pathways that govern cell proliferation and apoptosis. Recently, studies on the effects of GST genetic polymorphisms on COVID-19 disease development revealed that the individuals with higher numbers of risk-associated genotypes showed higher risk of COVID-19 prevalence and severity. Furthermore, overexpression of GSTs in many tumors is frequently associated with drug resistance phenotypes. These functional properties make these proteins promising targets for therapeutics, and a number of GST inhibitors have progressed in clinical trials for the treatment of cancer and other diseases.

GmGSTU23 Encoding a Tau Class Glutathione S-Transferase Protein Enhances the Salt Tolerance of Soybean (Glycine max L.).

Salt stress has a detrimental impact on crop yield, quality, and profitability. The tau-like glutathione transferases (GSTs) represent a significant group of enzymes that play a crucial role in plant stress responses, including salt stress. In this study, we identified a tau-like glutathione transferase family gene from soybean named GmGSTU23. Expression pattern analysis revealed that GmGSTU23 was predominantly expressed in the roots and flowers and exhibited a concentration-time-specific pattern in response to salt stress. Transgenic lines were generated and subjected to phenotypic characterization under salt stress. The transgenic lines exhibited increased salt tolerance, root length, and fresh weight compared to the wild type. Antioxidant enzyme activity and malondialdehyde content were subsequently measured, and the data revealed no significant differences between the transgenic and wild-type plants in the absence of salt stress. However, under salt stress, the wild-type plants exhibited significantly lower activities of SOD, POD, and CAT than the three transgenic lines, whereas the activity of APX and the content of MDA showed the opposite trend. We identified changes in glutathione pools and associated enzyme activity to gain insights into the underlying mechanisms of the observed phenotypic differences. Notably, under salt stress, the transgenic Arabidopsis's GST activity, GR activity, and GSH content were significantly higher than those of the wild type. In summary, our findings suggest that GmGSTU23 mediates the scavenging of reactive oxygen species and glutathione by enhancing the activity of glutathione transferase, thereby conferring enhanced tolerance to salt stress in plants.

Genome-Wide Identification and Expression Profiling of Glutathione S-Transferase Gene Family in Foxtail Millet (Setaria italica L.)

Glutathione S-transferases (GSTs) are a critical superfamily of multifunctional enzymes in plants. As a ligand or binding protein, GSTs regulate plant growth and development and detoxification. Foxtail millet (Setaria italica (L.) P. Beauv) could respond to abiotic stresses through a highly complex multi-gene regulatory network in which the GST family is also involved. However, GST genes have been scarcely studied in foxtail millet. Genome-wide identification and expression characteristics analysis of the foxtail millet GST gene family were conducted by biological information technology. The results showed that 73 GST genes (SiGSTs) were identified in the foxtail millet genome and were divided into seven classes. The chromosome localization results showed uneven distribution of GSTs on the seven chromosomes. There were 30 tandem duplication gene pairs belonging to 11 clusters. Only one pair of SiGSTU1 and SiGSTU23 were identified as fragment duplication genes. A total of ten conserved motifs were identified in the GST family of foxtail millet. The gene structure of SiGSTs is relatively conservative, but the number and length of exons of each gene are still different. The cis-acting elements in the promoter region of 73 SiGST genes showed that 94.5% of SiGST genes possessed defense and stress-responsive elements. The expression profiles of 37 SiGST genes covering 21 tissues suggested that most SiGST genes were expressed in multiple organs and were highly expressed in roots and leaves. By qPCR analysis, we found that 21 SiGST genes were responsive to abiotic stresses and abscisic acid (ABA). Taken together, this study provides a theoretical basis for identifying foxtail millet GST family information and improving their responses to different stresses.

Protective Effects of PEP-1-GSTA2 Protein in Hippocampal Neuronal Cell Damage Induced by Oxidative Stress.

Glutathione S-transferase alpha 2 (GSTA2), a member of the glutathione S-transferase family, plays the role of cellular detoxification against oxidative stress. Although oxidative stress is related to ischemic injury, the role of GSTA2 against ischemia has not been elucidated. Thus, we studied whether GSTA2 prevents ischemic injury by using the PEP-1-GSTA2 protein which has a cell-permeable protein transduction domain. We revealed that cell-permeable PEP-1-GSTA2 transduced into HT-22 cells and markedly protected cell death via the inhibition of reactive oxygen species (ROS) production and DNA damage induced by oxidative stress. Additionally, transduced PEP-1-GSTA2 promoted mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-κB) activation. Furthermore, PEP-1-GSTA2 regulated Bcl-2, Bax, cleaved Caspase-3 and -9 expression protein levels. An in vivo ischemic animal model, PEP-1-GSTA2, markedly prevented the loss of hippocampal neurons and reduced the activation of microglia and astrocytes. These findings indicate that PEP-1-GSTA2 suppresses hippocampal cell death by regulating the MAPK and apoptotic signaling pathways. Therefore, we suggest that PEP-1-GSTA2 will help to develop the therapies for oxidative-stress-induced ischemic injury.

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review.

Head and neck squamous cell carcinomas (HNSCCs) are associated with variable prognosis even with similar clinical characteristics and treatments. Gene polymorphisms have been suggested as prognostic factors for HNSCC which can justified this variable prognosis. So, the aim was to review literatures on gene polymorphisms and prognosis of HNSCCs. A systematic search was conducted using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases to find all related articles published up to December 2021 in the field of gene polymorphisms and HNSCC prognosis. Of 1029 initial searched articles, 71 articles were selected for inclusion in this systematic review. About 93 genes and 204 polymorphisms have been discussed in these articles. Among the most studied polymorphisms, the XRCC1 Arg399Gln and Arg194Trp polymorphisms were not associated with survival in most studies; the ERCC1 C19007T polymorphism had no significant association in any of the studies. Different gene polymorphisms of glutathione s-transferase family, including GSTM1 deletion, GSTT1 deletion and GSTP1 A313G, were not associated with survival in included studies. There are conflicting results regarding the association between polymorphisms such as ERCC2 A35931C, Asp312Asn, ERCC5 rs1047768 and rs17655 with HNSCC prognosis. Less studied polymorphisms, such as hOGG1 rs1052133 or the VEGF rs699947, were generally not associated with HNSCC prognosis. Reviewed articles reported varied and contradictory results regarding the association of gene polymorphisms and HNSCC prognosis, which necessitates further studies along with meta-analysis on the results of such studies.

Combating Drug Resistance by Exploiting miRNA-200c-Controlled Phase II Detoxification.

Acquired drug resistance constitutes a serious obstacle to the successful therapy of cancer. In the process of therapy resistance, microRNAs can play important roles. In order to combat resistance formation and to improve the efficacy of chemotherapeutics, the mechanisms of the multifaceted hsa-miR-200c on drug resistance were elucidated. Upon knockout of hsa-miR-200c in breast carcinoma cells, a proteomic approach identified altered expression of glutathione S-transferases (GSTs) when cells were treated with the chemotherapeutic drug doxorubicin. In different hsa-miR-200c expression systems, such as knockout, inducible sponge and inducible overexpression, the differential expression of all members of the GST family was evaluated. Expression of hsa-miR-200c in cancer cells led to the repression of a multitude of these GSTs and as consequence, enhanced drug-induced tumor cell death which was evaluated for two chemotherapeutic drugs. Additionally, the influence of hsa-miR-200c on the glutathione pathway, which is part of the phase II detoxification mechanism, was investigated. Finally, the long-term effects of hsa-miR-200c on drug efficacy were studied in vitro and in vivo. Upon doxycycline induction of hsa-miR-200c, MDA-MB 231 xenograft mouse models revealed a strongly reduced tumor growth and an enhanced treatment response to doxorubicin. A combined treatment of these tumors with hsa-miR-200c and doxorubicin resulted in complete regression of the tumor in 60% of the animals. These results identify hsa-miR-200c as an important player regulating the cellular phase II detoxification, thus sensitizing cancer cells not expressing this microRNA to chemotherapeutics and reversing drug resistance through suppression of GSTs.

Molecular characteristics of glutathione transferase gene family in a neglect medical Spirometra tapeworm.

The Spirometra mansoni is a neglect medical tapeworm, its plerocercoid larvae can parasitize in humans and animals, causing sparganosis. In this study, 17 new members of the glutathione transferase (GST) family were sequenced and characterized in S. mansoni. Clustering analysis displayed the categorization of SmGSTs into two main clades. RT-qPCR illustrated that 7 GST genes were highly expressed in the plerocercoid stage while 8 GSTs were highly expressed in the adult. rSmGST has the typical C- and N-terminal double domains of glutathione transferase. Immunolocalization revealed that natural SmGST is mainly located in the epidermis and parenchyma of plerocercoid, and in the epidermis, parenchyma, uterus and egg shell of adult worm. The optimum activity for rSmGST was found to be pH 6.5 and 25°C. The evolutionary tree showed a high level of diversity of cestodes GSTs. SmGSTs contained both conserved family members and members in the process of further diversification. The findings in this study will lay a foundation to better explore the underlying mechanisms of GSTs involved in Spirometra tapeworms.

Glutathione S-Transferases S1, Z1 and A1 Serve as Prognostic Factors in Glioblastoma and Promote Drug Resistance through Antioxidant Pathways.

The glutathione S-transferase (GST) family of detoxification enzymes can regulate the malignant progression and drug resistance of various tumors. Hematopoietic prostaglandin D synthase (HPGDS, also referred to as GSTS1), GSTZ1, and GSTA1 are abnormally expressed in multiple cancers, but their roles in tumorigenesis and development remain unclear. In this study, we used bioinformatics tools to analyze the connections of HPGDS, GSTZ1, and GSTA1 to a variety of tumors in genetic databases. Then, we performed biochemical assays in GBM cell lines to investigate the involvement of HPGDS in proliferation and drug resistance. We found that HPGDS, GSTZ1, and GSTA1 are abnormally expressed in a variety of tumors and are associated with prognoses. The expression level of HPGDS was significantly positively correlated with the grade of glioma, and high levels of HPGDS predicted a poor prognosis. Inhibiting HPGDS significantly downregulated GBM proliferation and reduced resistance to temozolomide by disrupting the cellular redox balance and inhibiting the activation of JNK signaling. In conclusion, this study suggested that HPGDS, GSTZ1, and GSTA1 are related to the progression of multiple tumors, and HPGDS is expected to be a prognostic factor in GBM.

Association of glutathione s-transferase pi (GSTP1) gene polymorphism in unexplained infertile women

15–20 million people in India are affected by infertility.Among them, 34% of the couples are shown to have unexplained infertility (UEI). Both genetic and environmental factors influence UEI. Data from various studies show that oxidative stress plays an important role in unexplained infertility. The genes of the phase II detoxification enzyme, Glutathione s-transferase family are upregulated in humans as a defense mechanism opposing the adverse effects of oxidative stress and play important role during pregnancy. Since all investigations for infertility work-up are normal evaluating the causes for UEI will have impact on the treatment protocol. In this study the association between GSTP1 variations and unexplained infertility are discussed. To compare the association of GSTP1 polymorphism in women with unexplained infertility and a control group.: This is a case control study with 70 normal ovulatory women who conceived within 12 months of contraceptive free intercourse, and with no history of miscarriage were recruited in the control group and 70 women with unexplained infertility were recruited as study group. All participants included in the study were between 28 and 38 years of age. The association of GSTP1 polymorphism were studied using real-time PCR with the Light Cycler instrument (Roche Applied Science).: GSTP1 variant allele frequencies were 0.39 and 0.41for control and cases respectively. The results of this study indicate GSTP1 genetic polymorphisms did not show a significant association with unexplained infertile group.

Longitudinal physiological and transcriptomic analyses reveal the short term and long term response of Synechocystis sp. PCC6803 to cadmium stress.

Due to the bioaccumulation and non-biodegradability of cadmium, Cd can pose a serious threat to ecosystem even at low concentration. Microalgae is widely distributed photosynthetic organisms in nature, which is a promising heavy metal remover and an effective industrial sewage cleaner. However, there are few detailed reports on the short-term and long-term molecular mechanisms of microalgae under Cd stress. In this study, the adsorption behavior (growth curve, Cd removal efficiency, scanning electron microscope, Fourier transform infrared spectroscopy, and dynamic change of extracellular polymeric substances), cytotoxicity (photosynthetic pigment, MDA, GSH, H2O2, O2-) and stress response mechanism of microalgae were discussed under EC50. RNA-seq detected 1413 DEGs in 4 treatment groups. These genes were related to ribosome, nitrogen metabolism, sulfur transporter, and photosynthesis, and which been proved to be Cd-responsive DEGs. WGCNA (weighted gene co-expression network analysis) revealed two main gene expression patterns, short-term stress (381 genes) and long-term stress (364 genes). The enrichment analysis of DEGs showed that the expression of genes involved in N metabolism, sulfur transporter, and aminoacyl-tRNA biosynthesis were significantly up-regulated. This provided raw material for the synthesis of the important component (cysteine) of metal chelate protein, resistant metalloprotein and transporter (ABC transporter) in the initial stage, which was also the short-term response mechanism. Cd adsorption of the first 15min was primary dependent on membrane transporter and beforehand accumulated EPS. Simultaneously, the up-regulated glutathione S-transferase (GSTs) family proteins played a role in the initial resistance to exogenous Cd. The damaged photosynthetic system was repaired at the later stage, the expressions of glycolysis and gluconeogenesis were up-regulated, to meet the energy and substances of physiological metabolic activities. The study is the first to provide detailed short-term and long-term genomic information on microalgae responding to Cd stress. Meanwhile, the key genes in this study can be used as potential targets for algae-mediated genetic engineering.