Compensation of Mutation in Arabidopsis glutathione transferase (AtGSTU) Genes under Control or Salt Stress Conditions

Glutathione transferases (GSTs) play a crucial role in detoxification processes due to the fact of their glutathione (GSH) conjugating activity, and through glutathione peroxidase or dehydroascorbate reductase (DHAR) activities, they influence the redox state of GSH and ascorbate (AsA). The plant-specific tau (GSTU) group is the largest class of Arabidopsis GSTs, and their members are involved in responses to different abiotic stresses. We investigated the effect of salt stress on two-week-old Arabidopsis thaliana wild-type (Col-0), Atgstu19 and Atgstu24 mutant plants after applying 150 mM NaCl for two days. The Atgstu19 seedlings had lower GST activity and vitality both under control conditions and after salt stress than the wild-type, but the level of total ROS was similar to the Col-0 plants. The GST activity of the knockout Atgstu24 mutant was even higher under control conditions compared to the Col-0 plants, while the ROS level and its vitality did not differ significantly from the wild-type. Analysis of the AtGSTU expression pattern revealed that the mutation in a single AtGSTU gene was accompanied by the up- and downregulation of several other AtGSTUs. Moreover, elevated AsA and GSH levels, an altered GSH redox potential and increased DHAR and glutathione reductase activities could help to compensate for the mutation of AtGSTU genes. The observed changes in the mutants suggest that the investigated isoenzymes influence the redox homeostasis under control conditions and after NaCl treatment in Arabidopsis seedlings. These data indicate for the first time the more general role of a temporary shift of redox status as part of GST mechanisms and regulation.

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Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.620690 ◽

2021 ◽

Vol 8 ◽

Author(s):

Veljko Santric ◽

Dejan Dragicevic ◽

Marija Matic ◽

Milica Djokic ◽

Marija Pljesa-Ercegovac ◽

...

Keyword(s):

Prostate Cancer ◽

Glutathione Transferase ◽

Redox Homeostasis ◽

Prostate Cancer Risk ◽

Gst Polymorphisms ◽

Increased Risk ◽

Genes Encoding ◽

Gst Polymorphism ◽

First Time

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs’ role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.

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Genome-wide identification of the GATA transcription factor family and their expression patterns under temperature and salt stress in Aspergillus oryzae

AMB Express ◽

10.1186/s13568-021-01212-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chunmiao Jiang ◽

Gongbo Lv ◽

Jinxin Ge ◽

Bin He ◽

Zhe Zhang ◽

...

Keyword(s):

Salt Stress ◽

Expression Patterns ◽

Interaction Network ◽

Protein Protein Interaction ◽

Genome Wide ◽

Gata Transcription Factor ◽

Starting Point ◽

Evolutionary Features ◽

First Time

AbstractGATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillusoryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A.oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X2-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A.oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein–protein interaction network of A.oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A.oryzae.

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Porcine glutathione transferase Alpha 2-2 is a human GST A3-3 analogue that catalyses steroid double-bond isomerization

Biochemical Journal ◽

10.1042/bj20100839 ◽

2010 ◽

Vol 431 (1) ◽

pp. 159-167 ◽

Cited By ~ 13

Author(s):

Natalia Fedulova ◽

Françoise Raffalli-Mathieu ◽

Bengt Mannervik

Keyword(s):

Double Bond ◽

Glutathione Transferase ◽

Biological Species ◽

Glutathione Transferases ◽

Special Role ◽

Primary Role ◽

The Novel ◽

Protective Function ◽

Isomerase Activity

A primary role of GSTs (glutathione transferases) is detoxication of electrophilic compounds. In addition to this protective function, hGST (human GST) A3-3, a member of the Alpha class of soluble GSTs, has prominent steroid double-bond isomerase activity. The isomerase reaction is an obligatory step in the biosynthesis of steroid hormones, indicating a special role of hGST A3-3 in steroidogenic tissues. An analogous GST with high steroid isomerase activity has so far not been found in any other biological species. In the present study, we characterized a Sus scrofa (pig) enzyme, pGST A2-2, displaying high steroid isomerase activity. High levels of pGST A2-2 expression were found in ovary, testis and liver. In its functional properties, other than steroid isomerization, pGST A2-2 was most similar to hGST A3-3. The properties of the novel porcine enzyme lend support to the notion that particular GSTs play an important role in steroidogenesis.

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Abstract P283: Parkin Mediates Mitophagy in Cardioprotection

Circulation Research ◽

10.1161/res.109.suppl_1.ap283 ◽

2011 ◽

Vol 109 (suppl_1) ◽

Author(s):

Allen M Andres ◽

Chengqun Huang ◽

Eric P Ratliff ◽

Genaro Hernandez ◽

Pamela Lee ◽

...

Keyword(s):

Ex Vivo ◽

Wild Type ◽

Simulated Ischemia ◽

Selective Targeting ◽

Cardioprotective Effects ◽

Mitochondrial Turnover ◽

First Time

Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining cellular homeostasis. However, the mechanisms that govern the selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown to be essential for the selective clearance of damaged mitochondria. Parkin is expressed in the heart, yet its function has not been investigated in the context of cardioprotection. We previously reported that autophagy is required for cardioprotection by ischemic preconditioning (IPC). In the present study, we used simulated ischemia in vitro and IPC in hearts (in vivo and ex vivo) to investigate the role of Parkin in mediating cardioprotection. In HL-1 cells, simulated ischemia induced Parkin translocation to mitochondria and mitochondrial elimination. Mitochondrial loss was blunted in Atg5-deficient cells, revealing the requirement for autophagy in mitochondrial elimination. Consistent with previous reports implicating p62/SQSTM1 in mitophagy, we found that downregulation of p62 attenuated mitophagy and exacerbated cell death in HL-1 cardiomyocytes subjected to simulated ischemia. While wild type mice showed p62 translocation to mitochondria after IPC, Parkin knockout mice exhibited attenuated translocation of p62 to mitochondria. Importantly, ablation of Parkin in mice abolished the cardioprotective effects of IPC. These results reveal for the first time the crucial role of Parkin and mitophagy in cardioprotection.

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Differential regulation of Ca2+ influx by ORAI channels mediates enamel mineralization

Science Signaling ◽

10.1126/scisignal.aav4663 ◽

2019 ◽

Vol 12 (578) ◽

pp. eaav4663 ◽

Cited By ~ 12

Author(s):

Miriam Eckstein ◽

Martin Vaeth ◽

Francisco J. Aulestia ◽

Veronica Costiniti ◽

Serena N. Kassam ◽

...

Keyword(s):

Consumption Rate ◽

Redox Homeostasis ◽

Direct Interaction ◽

Redox Status ◽

Cellular Functions ◽

Enamel Defects ◽

Targeted Deletion ◽

Anhidrotic Ectodermal Dysplasia ◽

Enamel Mineralization

Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular functions. Mutations in the human ORAI1 gene result in immunodeficiency, anhidrotic ectodermal dysplasia, and enamel defects. In our investigation of the role of ORAI proteins in enamel, we identified enamel defects in a patient with an ORAI1 null mutation. Targeted deletion of the Orai1 gene in mice showed enamel defects and reduced SOCE in isolated enamel cells. However, Orai2−/− mice showed normal enamel despite having increased SOCE in the enamel cells. Knockdown experiments in the enamel cell line LS8 suggested that ORAI2 and ORAI3 modulated ORAI1 function, with ORAI1 and ORAI2 being the main contributors to SOCE. ORAI1-deficient LS8 cells showed altered mitochondrial respiration with increased oxygen consumption rate and ATP, which was associated with altered redox status and enhanced ER Ca2+ uptake, likely due to S-glutathionylation of SERCA pumps. Our findings demonstrate an important role of ORAI1 in Ca2+ influx in enamel cells and establish a link between SOCE, mitochondrial function, and redox homeostasis.

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The PACAP-Regulated Gene Selenoprotein T Is Abundantly Expressed in Mouse and Human β-Cells and Its Targeted Inactivation Impairs Glucose Tolerance

Endocrinology ◽

10.1210/en.2013-1167 ◽

2013 ◽

Vol 154 (10) ◽

pp. 3796-3806 ◽

Cited By ~ 46

Author(s):

Gaëtan Prevost ◽

Arnaud Arabo ◽

Long Jian ◽

Eddy Quelennec ◽

Dorthe Cartier ◽

...

Keyword(s):

Glucose Tolerance ◽

Redox Status ◽

Human Islets ◽

Mutant Mice ◽

Wild Type ◽

Β Cells ◽

Cellular Processes ◽

Insulin Promoter ◽

Selenoprotein T

Selenoproteins are involved in the regulation of redox status, which affects several cellular processes, including cell survival and homeostasis. Considerable interest has arisen recently concerning the role of selenoproteins in the regulation of glucose metabolism. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein of the endoplasmic reticulum, is present at high levels in human and mouse pancreas as revealed by immunofluorescence and quantitative PCR. Confocal immunohistochemistry studies revealed that SelT is mostly confined to insulin- and somatostatin-producing cells in mouse and human islets. To elucidate the role of SelT in β-cells, we generated, using a Cre-Lox strategy, a conditional pancreatic β-cell SelT-knockout C57BL/6J mice (SelT-insKO) in which SelT gene disruption is under the control of the rat insulin promoter Cre gene. Glucose administration revealed that male SelT-insKO mice display impaired glucose tolerance. Although insulin sensitivity was not modified in the mutant mice, the ratio of glucose to insulin was significantly higher in the SelT-insKO mice compared with wild-type littermates, pointing to a deficit in insulin production/secretion in mutant mice. In addition, morphometric analysis showed that islets from SelT-insKO mice were smaller and that their number was significantly increased compared with islets from their wild-type littermates. Finally, we found that SelT is up-regulated by pituitary adenylate cyclase-activating polypeptide (PACAP) in β-pancreatic cells and that SelT could act by facilitating a feed-forward mechanism to potentiate insulin secretion induced by the neuropeptide. Our findings are the first to show that the PACAP-regulated SelT is localized in pancreatic β- and δ-cells and is involved in the control of glucose homeostasis.

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The role of an evolutionarily conserved cis-proline in the thioredoxin-like domain of human class Alpha glutathione transferase A1-1

Biochemical Journal ◽

10.1042/bj20021765 ◽

2003 ◽

Vol 372 (1) ◽

pp. 241-246 ◽

Cited By ~ 24

Author(s):

Chris NATHANIEL ◽

Louise A. WALLACE ◽

Jonathan BURKE ◽

Heini W. DIRR

Keyword(s):

Glutathione Transferase ◽

Conformational Stability ◽

Wild Type ◽

Catalytic Function ◽

Evolutionarily Conserved ◽

Glutathione S Transferases ◽

Equilibrium Unfolding ◽

The Stability ◽

Unfolding Kinetics

The thioredoxin-like fold has a βαβαββα topology, and most proteins/domains with this fold have a topologically conserved cis-proline residue at the N-terminus of β-strand 3. This residue plays an important role in the catalytic function and stability of thioredoxin-like proteins, but is reported not to contribute towards the stability of glutathione S-transferases (GSTs) [Allocati, Casalone, Masulli, Caccarelli, Carletti, Parker and Di Ilio (1999) FEBS Lett. 445, 347–350]. In order to further address the role of the cis-proline in the structure, function and stability of GSTs, cis-Pro-56 in human GST (hGST) A1-1 was replaced with a glycine, and the properties of the P56G mutant were compared with those of the wild-type protein. Not only was the catalytic function of the mutant dramatically reduced, so was its conformational stability, as indicated by equilibrium unfolding and unfolding kinetics experiments with urea as denaturant. These findings are discussed in the context of other thioredoxin-like proteins.

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Essential roles for Pot1b in HSC self-renewal and survival

Blood ◽

10.1182/blood-2011-06-361527 ◽

2011 ◽

Vol 118 (23) ◽

pp. 6068-6077 ◽

Cited By ~ 22

Author(s):

Yang Wang ◽

Mei-Feng Shen ◽

Sandy Chang

Keyword(s):

Progenitor Cell ◽

Essential Role ◽

Dyskeratosis Congenita ◽

Telomere Maintenance ◽

Wild Type ◽

Telomere Shortening ◽

Damage Response ◽

First Time

Abstract Maintenance of mammalian telomeres requires both the enzyme telomerase and shelterin, which protect telomeres from inappropriately activating DNA damage response checkpoints. Dyskeratosis congenita is an inherited BM failure syndrome disorder because of defects in telomere maintenance. We have previously shown that deletion of the shelterin component Pot1b in the setting of telomerase haploinsufficiency results in rapid telomere shortening and fatal BM failure in mice, eliciting phenotypes that strongly resemble human syskeratosis congenita. However, it was unclear why BM failure occurred in the setting of Pot1b deletion. In this study, we show that Pot1b plays an essential role in HSC survival. Deletion of Pot1b results in increased apoptosis, leading to severe depletion of the HSC reserve. BM from Pot1bΔ/Δ mice cannot compete with BM from wild-type mice to provide multilineage reconstitution, indicating that there is an intrinsic requirement for Pot1b the maintenance of HSC function in vivo. Elimination of the p53-dependent apoptotic function increased HSC survival and significantly extended the lifespan of Pot1b-null mice deficient in telomerase function. Our results document for the first time the essential role of a component of the shelterin complex in the maintenance of HSC and progenitor cell survival.

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The Arabidopsis glutathione transferases, AtGSTF8 and AtGSTU19 are involved in the maintenance of root redox homeostasis affecting meristem size and salt stress sensitivity

Plant Science ◽

10.1016/j.plantsci.2019.02.005 ◽

2019 ◽

Vol 283 ◽

pp. 366-374 ◽

Cited By ~ 9

Author(s):

Edit Horváth ◽

Krisztina Bela ◽

Botond Holinka ◽

Riyazuddin Riyazuddin ◽

Ágnes Gallé ◽

...

Keyword(s):

Salt Stress ◽

Redox Homeostasis ◽

Stress Sensitivity ◽

Glutathione Transferases ◽

Meristem Size

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Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages

Cells ◽

10.3390/cells8121476 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1476 ◽

Cited By ~ 1

Author(s):

Mojca Trstenjak Prebanda ◽

Janja Završnik ◽

Boris Turk ◽

Nataša Kopitar Jerala

Keyword(s):

Redox Homeostasis ◽

Redox Status ◽

Protective Role ◽

Protein Levels ◽

Lps Challenge ◽

Pyrin Domain ◽

Cysteine Cathepsins ◽

Peroxiredoxin 3 ◽

Superoxide Dismutase 2

Stefin B (cystatin B) is an intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht–Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease progression was impaired redox homeostasis. Stefin B-deficient mice were found more sensitive to lipopolysaccharide (LPS)-induced sepsis as a consequence of increased expression of caspase-11 and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing (NLRP nflammasome activation and higher levels of mitochondrial reactive oxygen species (ROS). In the present study, we investigated if LPS-triggered oxidative stress affected the protein levels and redox status of redox sensitive proteins—thioredoxin, peroxiredoxins, and superoxide dismutases in macrophages and spleens of LPS-injected mice. LPS challenge was found to result in a marked elevation in mitochondrial peroxiredoxin 3 (Prx3), sulfiredoxin, and superoxide dismutase 2 (Sod2) in stefin B-deficient macrophages and spleens. We determined that sulfiredoxin is targeted to mitochondria after LPS challenge. In conclusion, the upregulation of mitochondrial redox-sensitive proteins Prx3 and Sod2 in stefin B-deficient cells implies a protective role of stefin B in mitochondrial function.

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