Expression pattern of GSTP1 and GSTA1 in the pathogenesis of asthma

Sohn, Seong Wook; Jung, Jae Woo; Lee, Soo Yeon; Kang, Hye Ryun; Park, Heung-Woo; Min, Kyung Up; Cho, Sang Heon

doi:10.3109/01902148.2013.789572

Cited by 16 publications

(12 citation statements)

References 34 publications

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“…The ability of Pb to induce oxidative stress in lung cells in the current study is evidenced by the ability of Pb treatment to decrease the expression of GSTA1, a well-known antioxidant gene, and to increase the ROS generation. Our results were in agreement with previous studies showed that changes in the expression levels of antioxidant protein GSTA1 play a key role in the induction of lung inflammation (Rahman and Adcock 2006;Sohn et al 2013). Furthermore, a significant reduction in the antioxidant gene, GSTA1 mRNA expression level was demonstrated in people chronically exposed to environmental heavy metals (Al Bakheet et al 2013).…”

Section: Discussionsupporting

confidence: 93%

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Attafi

Bakheet

Korashy

2019

Toxicology Mechanisms and Methods

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Lead (Pb) is recognized as the first heavy metal of the top six toxic air pollutants threatening human health and the second hazardous substance. Pb exposure is associated with lung impairment and high incidences of lung cancer. Nuclear factor kappa B (NF-jB) and aryl hydrocarbon receptor (AhR) signaling pathways are known to be expressed and play an important role in the lung. However, the link between Pb lung toxicity and NF-jB and/or AhR pathways remains unclear. This study was established to explore the role of NF-jB and AhR modulation in Pb-induced lung toxicity in human lung cancer A549 cells. In the current study, treatment of A549 cells with Pb significantly induced cell apoptosis as evidenced by increasing a) the percentage of cells underwent apoptosis determined by flow cytometry and b) p53 mRNA level. Pb treatment induced oxidative stress by a) increasing the formation of reactive oxygen species and b) decreasing GSTA1 mRNA levels. The toxic effects of Pb on the lung was associated with significant increases in NF-jB and AhR levels which was accompanied with increases in downstream targets genes, iNOS and CYP1A1, respectively. Inhibition of NF-jB or AhR either chemically using resveratrol or genetically using small interfering RNA (siRNA) significantly rescued A549 cells from Pb-mediated lung toxicity. The results clearly indicate that Pb-mediated lung toxicities are NF-jB and AhR-dependent mechanism.

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Section: Discussionsupporting

confidence: 93%

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Attafi

Bakheet

Korashy

2019

Toxicology Mechanisms and Methods

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“…In addition to GSTP, other GSTs have been linked to inflammatory lung diseases and NF-κB activation. In addition to GSTP, GSTA and GSTM are also expressed in lung epithelial cells [38] . A recent study demonstrated that GSTM positive humans display higher NF-κB activity and airway neutrophilia following allergen challenge, as compared to GSTM deficient humans [39] .…”

Section: Discussionmentioning

confidence: 99%

Glutathione S-transferase pi modulates NF-κB activation and pro-inflammatory responses in lung epithelial cells

et al. 2016

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Nuclear Factor kappa B (NF-κB) is a transcription factor family critical in the activation of pro- inflammatory responses. The NF-κB pathway is regulated by oxidant-induced post-translational modifications. Protein S-glutathionylation, or the conjugation of the antioxidant molecule, glutathione to reactive cysteines inhibits the activity of inhibitory kappa B kinase beta (IKKβ), among other NF-κB proteins. Glutathione S-transferase Pi (GSTP) is an enzyme that has been shown to catalyze protein S-glutathionylation (PSSG) under conditions of oxidative stress. The objective of the present study was to determine whether GSTP regulates NF-κB signaling, S-glutathionylation of IKK, and subsequent pro-inflammatory signaling. We demonstrated that, in unstimulated cells, GSTP associated with the inhibitor of NF-κB, IκBα. However, exposure to LPS resulted in a rapid loss of association between IκBα and GSTP, and instead led to a protracted association between IKKβ and GSTP. LPS exposure also led to increases in the S-glutathionylation of IKKβ. SiRNA-mediated knockdown of GSTP decreased IKKβ-SSG, and enhanced NF-κB nuclear translocation, transcriptional activity, and pro-inflammatory cytokine production in response to lipopolysaccharide (LPS). TLK117, an isotype-selective inhibitor of GSTP, also enhanced LPS-induced NF-κB transcriptional activity and pro-inflammatory cytokine production, suggesting that the catalytic activity of GSTP is important in repressing NF-κB activation. Expression of both wild-type and catalytically-inactive Y7F mutant GSTP significantly attenuated LPS- or IKKβ-induced production of GM-CSF. These studies indicate a complex role for GSTP in modulating NF-κB, which may involve S-glutathionylation of IKK proteins, and interaction with NF-κB family members. Our findings suggest that targeting GSTP is a potential avenue for regulating the activity of this prominent pro-inflammatory and immunomodulatory transcription factor.

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“…This is the case of glutathione S-transferases (GSTs), a supergene family implicated in detoxification of reactive oxygen species that appear to be related to asthma susceptibility [31]. Apparently, some mutations of GSTs may be related to asthma onset and AHR, however, contradictory data was found depending on the study group [32,33]. In fact, Piacentini et al [32] did not find an association between GSTT, GSTM and GSTP (glutathion S-transferases) gene polymorphisms and the development of asthma in an adult Italian population.…”

Section: Clinical Biomarkers Associated With Allergic Asthmamentioning

confidence: 99%

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field

Villaseñor

Rosace

Obeso

et al. 2017

Clin Experimental Allergy

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Allergic asthma is a prominent disease especially during childhood. Indoor allergens, in general, and particularly house dust mites (HDM) are the most prevalent sensitizers associated with allergic asthma. Available data show that 65-130 million people are mite-sensitized world-wide and as many as 50% of these are asthmatic. In fact, sensitization to HDM in the first years of life can produce devastating effects on pulmonary function leading to asthmatic syndromes that can be fatal. To date, there has been considerable research into the pathological pathways and structural changes associated with allergic asthma. However, limitations related to the disease heterogeneity and a lack of knowledge into its pathophysiology have impeded the generation of valuable data needed to appropriately phenotype patients and, subsequently, treat this disease. Here, we report a systematic and integral analysis of the disease, from airway remodelling to the immune response taking place throughout the disease stages. We present an overview of metabolomics, the management of complex multifactorial diseases through the analysis of all possible metabolites in a biological sample, obtaining a global interpretation of biological systems. Special interest is placed on the challenges to obtain biological samples and the methodological aspects to acquire relevant information, focusing on the identification of novel biomarkers associated with specific phenotypes of allergic asthma. We also present an overview of the metabolites cited in the literature, which have been related to inflammation and immune response in asthma and other allergy-related diseases.

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Expression pattern of GSTP1 and GSTA1 in the pathogenesis of asthma

Cited by 16 publications

References 34 publications

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Glutathione S-transferase pi modulates NF-κB activation and pro-inflammatory responses in lung epithelial cells

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field

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