Expression of glutathione<i>S</i>-transferase variants in human airway wall after long-term response to sulfur mustard

Nourani, Mohammad Reza; Azimzadeh, Sadegh; Ghanei, Mostafa; Fooladi, Abbas Ali Imani

doi:10.3109/10799893.2013.864677

Cited by 11 publications

(6 citation statements)

References 43 publications

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“…A previous study revealed that activation of autophagy in HCC could contribute to the tolerance of oxaliplatin via regulation of the level of reactive oxygen species (ROS) ( 28 ). It has been demonstrated that GSTs serve an important function in cellular protection against oxidative stress in the respiratory tract via inhibition of the endogenous production of ROS, which is increased by exposure to sulfur mustard ( 36 ). Thus, it is speculated that regulation of ROS levels may involve GSTM1 and autophagic activity.…”

Section: Discussionmentioning

confidence: 99%

Autophagy activation contributes to glutathione transferase Mu 1‑mediated chemoresistance in hepatocellular carcinoma

Song

Zhou

et al. 2018

Oncol Lett

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Glutathione transferase Mu 1 (GSTM1) induces cancer drug resistance by hydrolyzing cancer chemotherapeutics or activating the anti-apoptosis pathway. However, the chemoresistance-inducing mechanism of GSTM1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of GSTM1 was examined in three HCC cell lines. Oxaliplatin and sorafenib were selected as chemotherapeutic agents. Small interfering RNA was used to decrease GSTM1 expression. Cell death was measured using MTT and annexin V/propidium iodide assays. Activation of autophagy was evaluated by green fluorescent protein-light chain 3 redistribution and analysis of autophagy-related 5 expression in MHCC97-H and Huh-7 cells. A stepwise increase in GSTM1 expression with increasing metastatic potential of HCC cell lines was revealed. Cell death induced by oxaliplatin and sorafenib was significantly increased following GSTM1-knockdown in MHCC97-H and Huh-7 cells. Activation of autophagy was significantly inhibited by silencing GSTM1 expression. The results of the present study suggest that GSTM1 may protect HCC cells against the effect of oxaliplatin treatment through activating autophagy. The present study provides a novel perspective on HCC drug-resistance.

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Section: Discussionmentioning

confidence: 99%

Autophagy activation contributes to glutathione transferase Mu 1‑mediated chemoresistance in hepatocellular carcinoma

Song

Zhou

et al. 2018

Oncol Lett

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“…Recent investigations have indicated that SM also reduces the glutathione peroxidase (GPX) activity in lung tissue either at chronic or acute phases. , It is a selenocysteine-containing enzyme that converts lipid and hydrogen peroxides to their corresponding alcohols and catalyzes the reducing of H 2 O 2 to H 2 O by utilizing GSH . Decreased activity of glutathione-s-transferase (GST) and glutathione reductase (GSR) enzymes has been also reported after SM exposure. ,, In a more recent study, Tahmasbpour et al have revealed higher expression of SOD , CAT , GST , GSS , and GPX mRNAs in lung biopsies of patients several years after SM exposure. However, they did not consider the expression of these antioxidants at the protein levels.…”

Section: Decreased Activity Of Antioxidant Enzymesmentioning

confidence: 99%

“…A large number of studies have considered the effect of SM on expression and activity of various antioxidant enzymes at chronic phase of injury . Although some studies have shown overexpression of different enzymatic antioxidants at the mRNA level, the activity of these enzymes or their expression at the protein level has been reported to be decreased long years after exposure to SM …”

Section: Decreased Activity Of Antioxidant Enzymesmentioning

confidence: 99%

“…38 Although some studies have shown overexpression of different enzymatic antioxidants at the mRNA level, the activity of these enzymes or their expression at the protein level has been reported to be decreased long years after exposure to SM. 39 Superoxide dismutase (SOD) is one of the most important antioxidants because it converts anionic superoxide (O 2…”

Section: Enzymesmentioning

confidence: 99%

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Free Radical Production and Oxidative Stress in Lung Tissue of Patients Exposed to Sulfur Mustard: An Overview of Cellular and Molecular Mechanisms

Harchegani

Tahmasbpour

Borna

et al. 2018

Chem. Res. Toxicol.

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Sulfur mustard (SM) is a chemical alkylating compound that primary targets lung tissue. It causes a wide variety of pathological effects in respiratory system such as chronic bronchitis, bronchiolitis obliterans, necrosis of the mucosa and inflammation, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. However, molecular and cellular mechanisms for these pathologies are still unclear. Oxidative stress (OS) induced by reactive oxygen species (ROS) is likely a significant mechanism by which SM leads to cell death and tissues injury. SM can trigger various molecular and cellular pathways that are linked to ROS generation, OS, and inflammation. Hypoxia-induced oxidative stress, reduced activity of enzymatic antioxidants, depletion of intercellular glutathione (GSH), decreased productivity of GSH-dependent antioxidants, mitochondrial dysfunction, accumulation of leukocytes and proinflammatory cytokines, and increased expression of ROS producing-related enzymes and inflammatory mediators are the major events in which SM leads to massive production of ROS and OS in pulmonary system. Therefore, understanding of these molecules and signaling pathways gives us valuable information about toxicological effects of SM on injured tissues and the way for developing a suitable clinical treatment. In this review, we aim to discuss the possible mechanisms by which SM induces excessive production of ROS, OS, and antioxidants depletion in lung tissue of exposed patients.

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“…The expression of antioxidants and ROS-producing genes was significantly altered in lung tissue of SM-exposed patients (Tahmasbpour et al, 2016). Overexpression of the glutathione S-transferase (GST) variants GSTA1, GSTM1 and GSTP1 was shown in the human airway wall as a long-term response to SM (Nourani et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Sulfur mustard resistant keratinocytes obtained elevated glutathione levels and other changes in the antioxidative defense mechanism

et al. 2018

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Background: Sulfur mustard (SM) is a potent blistering chemical warfare agent, which was first used in 1917. Despite the Chemical Weapons Convention, a use was recently reported in Syria in 2015. This emphasizes the importance to develop countermeasures against chemical warfare agents. Despite intensive research, there is still no antidote or prophylaxis available against SM. Methods: The newly developed SM-resistant keratinocyte cell line HaCaT/SM was used to identify new target structures for drug development, particularly the adaptations in protective measures against oxidative stress. For this purpose, glutathione (GSH) and NAD(P)H levels, the effect of glutathione S-transferase (GST) inhibition as well as activation and expression of Nrf2, GST, glutamate cysteine ligase (GCL) and glutathione-disulfide reductase (GSR) as well as multi-drug resistance (MDR) proteins 1, 3 and 5 were investigated. Results: The HaCaT/SM cells showed not only a better survival after treatment with SM or cytostatic drugs, but also hydrogen peroxide (H2O2). They exhibit more GSH even after SM treatment. Nrf2 levels were significantly lower. Inhibition of GST led to significantly decreased, activation to slightly higher IC50 values after SM treatment and a lower expression of GST was observed. The cells also expressed less GCLC and GSR. Expression of MDR1, MDR3 and MDR5 was higher under control conditions, but less stimulated by SM treatment. An increased NADP+/NADPH ratio as well as higher NAD+ levels were shown. Conclusion: In summary, an improved response of the resistant cell line to oxidative stress was observed. The underlying mechanisms are elevated GSH levels as well as lower expression of Nrf2 and its targets GCLC and GST as well as GSR and MDR1, MDR3 and MDR5. GST is an especially interesting target because its inhibition already induced a significant SM sensitivity. SM resistance also caused redox equivalent level differences. Taken together, these findings provide further insight into the mechanism of SM resistance and may open a window for novel therapeutic targets in SM therapy.

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Expression of glutathioneS-transferase variants in human airway wall after long-term response to sulfur mustard

Abstract: According to these findings, we speculated that overexpression of GSTs mRNA in patients revealed that GSTs plays an important role in cellular protection against oxidative stress of MS in airway wall of patients.

Cited by 11 publications

References 43 publications

Autophagy activation contributes to glutathione transferase Mu 1‑mediated chemoresistance in hepatocellular carcinoma

Autophagy activation contributes to glutathione transferase Mu 1‑mediated chemoresistance in hepatocellular carcinoma

Free Radical Production and Oxidative Stress in Lung Tissue of Patients Exposed to Sulfur Mustard: An Overview of Cellular and Molecular Mechanisms

Sulfur mustard resistant keratinocytes obtained elevated glutathione levels and other changes in the antioxidative defense mechanism

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