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Last update 08 May 2025

MGST2

Last update 08 May 2025

Basic Info

Synonyms

Glutathione peroxidase MGST2, GST2, Leukotriene C4 synthase MGST2

+ [6]

Introduction

Catalyzes several different glutathione-dependent reactions (PubMed:23409838, PubMed:26066610, PubMed:26656251, PubMed:8703034, PubMed:9278457). Catalyzes the glutathione-dependent reduction of lipid hydroperoxides, such as 5-HPETE (PubMed:23409838, PubMed:9278457). Has glutathione transferase activity, toward xenobiotic electrophiles, such as 1-chloro-2, 4-dinitrobenzene (CDNB) (PubMed:23409838, PubMed:8703034). Catalyzes also the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4 (LTC4) (PubMed:23409838, PubMed:26656251). Involved in oxidative DNA damage induced by ER stress and anticancer agents by activating LTC4 biosynthetic machinery in nonimmune cells (PubMed:26656251).

Drugs associated with MGST2

HG-1067

Target

MGST2

Mechanism

MGST2 gene modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Immune System Diseases [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MGST2

100 Translational Medicine associated with MGST2

0 Patents (Medical) associated with MGST2

Literatures (Medical) associated with MGST2

01 Feb 2025·Journal of Bone Oncology

Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway

Article

Author: Li, Yingang ; Bai, Xizhuang

Osteosarcoma is a common malignant tumor found in adolescents, characterized by a high metastatic potential and poor prognosis, but it is sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of regulated cell death induced by excessive iron accumulation, leading to lipid peroxidation that results in cellular dysfunction and death. Naringenin is a flavonoid known for its anti-cancer properties, yet its role in osteosarcoma has not been thoroughly studied. In this study, we found that naringenin significantly reduced the viability of osteosarcoma cells while increasing the accumulation of reactive oxygen species (ROS), iron overload, and the excessive expression of malondialdehyde (MDA). Bioinformatics analysis revealed that microsomal glutathione S-transferase 2 (MGST2) is highly expressed in osteosarcoma cells. Silencing MGST2 decreased the proliferation, migration, and invasion of these cells and enhanced their sensitivity to ferroptosis. Mechanistically, signal transducer and activator of transcription 3 (STAT3) binds to the MGST2 promoter, promoting its transcription. Naringenin inhibits STAT3, blocking the expression of MGST2, while the STAT3 agonist Colivelin reverses this effect. In vivo experiments further confirmed that naringenin inhibited tumor growth in subcutaneous xenograft models and exhibited good biosafety. In summary, our study demonstrates that naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway, providing a promising strategy for osteosarcoma treatment.

01 Feb 2025·Pharmaceutical Research

Structure Bioinformatics of Six Human Integral Transmembrane Enzymes and their AlphaFold3 Predicted Water-Soluble QTY Analogs: Insights into FACE1 and STEA4 Binding Mechanisms

Article

Author: Pan, Emily ; Zhang, Shuguang ; Chen, Edward

AbstractObjectiveHuman integral membrane enzymes are essential for catalyzing a wide range of biochemical reactions and regulating key cellular processes. However, studying these enzymes remains challenging due to their hydrophobic nature, which necessitates the use of detergents. This study explores whether applying the QTY code can reduce the hydrophobicity of these enzymes while preserving their structures and functions, thus facilitating bioinformatics analysis of six key integral membrane enzymes: MGST2, LTC4S, PTGES, FACE1, STEA4, and SCD.MethodsThe water-soluble QTY analogs of the six membrane enzymes were predicted using AlphaFold3. The predicted structures were superposed with CyroEM determined native structures in PyMOL to observe changes in structure and protein-ligand binding ability.ResultsThe native membrane enzymes superposed well with their respective QTY analogs, with the root mean square deviation (RMSD) ranging from 0.273 Å to 0.875 Å. Surface hydrophobic patches on the QTY analogs were significantly reduced. Importantly, the protein-ligand interactions in FACE1 and STEA4 were largely preserved, indicating maintained functionality.ConclusionOur structural bioinformatics studies using the QTY code and AlphaFold3 not only provide the opportunities of designing more water-soluble integral membrane enzymes, but also use these water-soluble QTY analogs as antigens for therapeutic monoclonal antibody discovery to specifically target the key integral membrane enzymes.

01 Feb 2025·Journal of Trace Elements in Medicine and Biology

Ameliorative role of Tetrapleura tetraptera (Schum. & Thonn.) taub in cadmium chloride-induced oxidative stress in Drosophila melanogaster using in vivo and computational approaches

Article

Author: Taiwo, Odunayo A ; Oyibo, Aghogho ; Adebayo, Adesewa C ; Osoniyi, Omolaja

BACKGROUNDCadmium (Cd) is a naturally occurring transition metal associated with oxidative stress in living organisms. Whereas Tetrapleura tetraptera (Tt), an ethnomedicinal plant is said to possess high antioxidant activity and used to treat various human diseases locally. Therefore, the study aimed to investigate the biological activity of the ethanolic pod extract of T. tetraptera in cadmium chloride-induced toxicity in Drosophila melanogaster.METHODSSix groups of adults (1-3 days old) D. melanogaster as shown: Control, Tt 2.5 mg/10 g diet, Tt 5 mg/10 g diet, CdCl₂, CdCl₂+ Tt 2.5 mg/10 diet and CdCl₂+Tt 5 mg/10 g diet were exposed via diet for 7 days consisting of 50 flies per vial and 5 replicate per group. Thereafter, we evaluated markers for free radical generation, antioxidant, non-antioxidant activities, and emergence rates of the flies. The active compounds of Tt extract were molecularly docked against glutathione-S-transferase II.RESULTSThe results indicated that CdCl₂ significantly induced oxidative stress by increasing the levels of lipid peroxidation (LPO), hydrogen peroxide (H₂O₂)_, nitric oxide (NO) and decreasing the activity of GST without an effect on total thiol (T-SH) and non-protein thiols (NP-SHs) levels. However, co-treatment with T. tetraptera (2.5 mg/10 g diet) significantly decreased levels of LPO, H₂O_2, but increased GST activity. Also, co-treatment with T. tetraptera (5 mg/10 g diet) increased NPSH and T-SH levels by 18.6 % and 35.8 %. Furthermore, Co-treatment (5 mg/10 g diet) increased the rate of offspring emergence.CONCLUSIONT. tetraptera ameliorated cadmium chloride-induced oxidative stress in Drosophila melanogaster and increased offspring hatching rate. T. tetraptera may therefore serve as a good regimen for the treatment of oxidative stress-related diseases induced by cadmium.

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MGST2

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