Glutathione transferases from parasites: A biochemical view

Torres-Rivera, Anayetzin; Landa, Abraham

doi:10.1016/j.actatropica.2007.08.005

Cited by 75 publications

(75 citation statements)

References 78 publications

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“…Based on their cellular location, GSTs are grouped into three families: mitochondrial GST, microsomal GSTs, now designated membrane-associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) and cytosolic GSTs. Microsomal GSTs bear no obvious resemblance to mitochondrial and cytosolic GSTs in terms of amino-acid sequence, molecular weight, or tertiary and quaternary structures (Ji et al, 2002;Torres-Rivera and Landa, 2008). For example, while mitochondrial and cytosolic GSTs exist as heterodimers or homodimers of subunits of 199-244 (23-27 kDa) and 226 amino acids respectively, microsomal GSTs may exist as monomers, homodimers, heterodimers, homotrimers or multimers of subunits of 14-17 kDa (137-150 amino acids) (Blanchette et al, 2007;Hayes et al, 2005;Ji et al, 2002;Kim et al, 2008;Morgenstern et al, 1985).…”

Section: Classification and Nomenclaturementioning

confidence: 99%

Glutathione and Glutathione‐S‐Transferase in Detoxification Mechanisms

2009

General, Applied and Systems Toxicology

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Glutathione (GSH) and glutathione‐S‐transferases (GSTs) are two primary lines of defence against both acute and chronic toxicities of electrophiles and reactive oxygen/nitrogen species. GSH confers cellular protection by directly or enzymatically reducing free radicals and reactive species (RS), and conjugating endogenous and exogenous electrophiles. GSTs are a superfamily of Phase 2 detoxification enzymes that detoxify both RS and toxic xenobiotics, primarily by catalysing GSH‐dependent conjugation and redox reactions. Both GSH content and GST enzyme activities are under tight homeostatic control. Under normal conditions, neither GST enzyme activities nor GSH levels operate at their maximum capacity. Upon exposure to mild oxidative and electrophilic stress, they are concomitantly induced to achieve efficient protection. This chapter provides an updated understanding about GSH synthesis, the utilization of GSH for detoxification against RS, drugs and toxic xenobiotics, and its recycling from glutathione disulfide (GSSG) and GSH conjugates. This chapter also reviews the united classification/nomenclature system, structure, catalytic mechanism and functions of GST enzymes. Another focus of this chapter is the well‐characterized antioxidant response element (ARE)/nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)‐Kelch‐like ECH associating protein 1 (Keap1) signalling pathway that regulates the basal and induced expression of GST and GSH homeostasis genes in mammals.

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Section: Classification and Nomenclaturementioning

confidence: 99%

Glutathione and Glutathione‐S‐Transferase in Detoxification Mechanisms

2009

General, Applied and Systems Toxicology

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“…The glutathione S-transferases (GSTs) are a versatile protein superfamily involved in cellular detoxification by either catalyzing toxin conjugation with glutathione (GSH) or passively binding to a wide range of endogenous/exogenous toxic molecules, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress (57). Parasite GSTs are believed to be involved in the detoxification of endogenously produced toxic compounds or host immune-initiated reactive oxygen species (ROS), as well as the transportation or metabolism of a variety of essential materials for parasites (57).…”

mentioning

confidence: 99%

“…Parasite GSTs are believed to be involved in the detoxification of endogenously produced toxic compounds or host immune-initiated reactive oxygen species (ROS), as well as the transportation or metabolism of a variety of essential materials for parasites (57). Due to their critical roles in parasite-host interactions, GSTs have been targeted for pharmaceutical and vaccine purposes and have demonstrated protective effects against some parasites (11,17,34).…”

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Molecular Cloning, Biochemical Characterization, and Partial Protective Immunity of the Heme-Binding GlutathioneS-Transferases from the Human HookwormNecator americanus

et al. 2010

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Hookworm glutathione S-transferases (GSTs) are critical for parasite blood feeding and survival and represent potential targets for vaccination. Three cDNAs, each encoding a full-length GST protein from the human hookworm Necator americanus (and designated Na-GST-1, Na-GST-2, and Na-GST-3, respectively) were isolated from cDNA based on their sequence similarity to Ac-GST-1, a GST from the dog hookworm Ancylostoma caninum. The open reading frames of the three N. americanus GSTs each contain 206 amino acids with 51% to 69% sequence identity between each other and Ac-GST-1. Sequence alignment with GSTs from other organisms shows that the three Na-GSTs belong to a nematode-specific nu-class GST family. All three Na-GSTs, when expressed in Pichia pastoris, exhibited low lipid peroxidase and glutathione-conjugating enzymatic activities but high heme-binding capacities, and they may be involved in the detoxification and/or transport of heme. In two separate vaccine trials, recombinant Na-GST-1 formulated with Alhydrogel elicited 32 and 39% reductions in adult hookworm burdens (P < 0.05) following N. americanus larval challenge relative to the results for a group immunized with Alhydrogel alone. In contrast, no protection was observed in vaccine trials with Na-GST-2 or Na-GST-3. On the basis of these and other preclinical data, Na-GST-1 is under possible consideration for further vaccine development.

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“…Glutathione S-transferases (GST) are ubiquitous proteins whose primary function is related to detoxification of endo-and exogenous toxic molecules, thus protecting cells from oxidative stress (34,35). Previous studies demonstrated that GBS is capable of triggering oxidative burst in mammalian cells (11,36).…”

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confidence: 99%

Group B Streptococcus induces tyrosine phosphorylation of annexin V and glutathione S-transferase in human umbilical vein endothelial cells

Santos

Penha²,

Mattos‐Guaraldi³

et al. 2009

Int J Mol Med

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Abstract. Group B Streptococcus (GBS), a human pathogen that causes infection and invasive diseases in newborns, pregnant women and immunocompromised adults, has been shown to invade human umbilical vein endothelial cells (HUVECs). The objective of this study was to investigate the molecular mechanisms underlying GBS-HUVEC interaction, focusing specifically on the responsiveness of host protein tyrosine kinase (PTK). We found that GBS serotypes III and V induced actin reorganization and formation of stress fibers into HUVECs. Since rearrangements of the actin cytoskeleton into eukaryotic cells are usually associated with the activation of PTK, we decided to follow the expression of this class of kinases in the course of the interaction. Unexpectedly, treatment of HUVECs with genistein greatly increased both cytoadherence and intracellular viability, for all GBS strains studied. GBS increased tyrosine phosphorylation of two proteins with an apparent molecular mass of 35 and 23 kDa in HUVECs as demonstrated by Western blot analysis with antiphosphotyrosine antibodies. Mass spectra analysis identified these proteins as annexin V and glutathione S-transferase. Studies are in progress to identify the role of these two proteins on GBS-HUVEC interaction.

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Glutathione transferases from parasites: A biochemical view

Cited by 75 publications

References 78 publications

Glutathione and Glutathione‐S‐Transferase in Detoxification Mechanisms

Glutathione and Glutathione‐S‐Transferase in Detoxification Mechanisms

Molecular Cloning, Biochemical Characterization, and Partial Protective Immunity of the Heme-Binding GlutathioneS-Transferases from the Human HookwormNecator americanus

Group B Streptococcus induces tyrosine phosphorylation of annexin V and glutathione S-transferase in human umbilical vein endothelial cells

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