Influence of glutathione-<i>S</i>-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism

Fletcher, Marianne E.; Boshier, Piers R; Wakabayashi, Kenji; Keun, Hector C.; Smolenski, Ryszard T.; Kirkham, Paul; Adcock, Ian M.; Barton, Paul J.R.; Takata, Masao; Marczin, Nándor

doi:10.1152/ajplung.00220.2014

Cited by 26 publications

(18 citation statements)

References 50 publications

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“…Looking at detoxification enzymes of the glutathione family, GSTP1 is a phase 2 enzyme involved in xenobiotic metabolism, antioxidant defense and maintenance of the cellular redox hemostasis [25,26]. GSTP1 catalyzes the conjugation of hydrophobic and electrophilic compounds with reduced glutathione [26] and loss of this enzyme has been associated with nuclear oxidative stress damage and potentiation of cell injury by ROS such as those released by TS [35,36].…”

Section: Discussionmentioning

confidence: 99%

Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure

Kaisar

Sivandzade

Bhalerao

et al. 2018

Neuroscience Letters

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It is well established that tobacco smoking is associated with vascular endothelial dysfunction in a causative and dose dependent manner primarily related to the tobacco smoke (TS) content of reactive oxygen species (ROS), nicotine, and oxidative stress (OS) -driven inflammation. Preclinical studies have also shown that nicotine (the principal e-liquid's ingredient used in e-cigarettes (e-Cigs) can also cause OS, exacerbation of cerebral ischemia and secondary brain injury. Likewise, chronic e-Cig vaping could be prodromal to vascular endothelial dysfunctions. Herein, we provide direct evidence that similarly to TS, e-Cig promotes mitochondrial depolarization in primary brain vascular endothelial cells as well as the vascular endothelial cell line bEnd3. In addition, both TS and e-Cig exposure upregulated the transmembrane iron exporter Slc40a1 (crucial to maintain cellular iron and redox homeostasis) and that of porphyrin importer Abcb6 (linked to accelerated atherosclerosis). We then investigated in vivo whether gender plays a role in how chronic TS affect vascular endothelial functions. Our results clearly show chronic TS exposure differentially impacts the expression levels of Phase-II enzymes as well as the iron transporters previously investigated in vitro. Although the physiological implications of the gender-specific differential responses to TS are not fully clear, they do demonstrate that gender is a risk factor that needs to be investigated when assessing the potential impact of chronic smoking and perhaps e-Cig vaping.

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Section: Discussionmentioning

confidence: 99%

Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure

Kaisar

Sivandzade

Bhalerao

et al. 2018

Neuroscience Letters

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“…We found that these nonlinearly expressed genes selected by NDC ( Figure 7E) were enriched in the ten terms, and these terms have no overlap between other terms enriched by reference methods. However, for the glutathione conjugation term, Fletcher et al (2015) reported that glutathione-S-transferases (GSTs) catalyze the conjugation of glutathione with toxic oxidant compounds and were associated with acute and chronic inflammatory lung diseases. For the glycerophospholipid metabolism term, phosphoenolpyruvate carboxykinase (PEPCK) has been shown to promote cancer cell survival under conditions of nutrient deprivation, a typical feature in solid cancers, as well as cancer growth (Méndez-Lucas et al, 2014;Leithner et al, 2015;Montal et al, 2015;Vincent et al, 2015).…”

Section: Enrichment Analysis Of Pathways and Biological Processesmentioning

confidence: 99%

A Novel Method to Efficiently Highlight Nonlinearly Expressed Genes

et al. 2020

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For precision medicine, there is a need to identify genes that accurately distinguish the physiological state or response to a particular therapy, but this can be challenging. Many methods of analyzing differential expression have been established and applied to this problem, such as t-test, edgeR, and DEseq2. A common feature of these methods is their focus on a linear relationship (differential expression) between gene expression and phenotype. However, they may overlook nonlinear relationships due to various factors, such as the degree of disease progression, sex, age, ethnicity, and environmental factors. Maximal information coefficient (MIC) was proposed to capture a wide range of associations of two variables in both linear and nonlinear relationships. However, with MIC it is difficult to highlight genes with nonlinear expression patterns as the genes giving the most strongly supported hits are linearly expressed, especially for noisy data. It is thus important to also efficiently identify nonlinearly expressed genes in order to unravel the molecular basis of disease and to reveal new therapeutic targets. We propose a novel nonlinearity measure called normalized differential correlation (NDC) to efficiently highlight nonlinearly expressed genes in transcriptome datasets. Validation using six real-world cancer datasets revealed that the NDC method could highlight nonlinearly expressed genes that could not be highlighted by t-test, MIC, edgeR, and DEseq2, although MIC could capture nonlinear correlations. The classification accuracy indicated that analysis of these genes could adequately distinguish cancer and paracarcinoma tissue samples. Furthermore, the results of biological interpretation of the identified genes suggested that some of them were involved in key functional pathways associated with cancer progression and metastasis. All of this evidence suggests that these nonlinearly expressed genes may play a central role in regulating cancer progression.

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“…We would expect a slower aging process because of partial de-repression of the HH pathway in Hhip +/− mice (22), whereas we observed accelerated aging-associated emphysema and increased cellular senescence in Hhip +/− mice. By searching for additional interacting proteins of HHIP, we identified GSTP1, a detoxification gene, which protects murine lung epithelial cells from H 2 O 2 -induced cell death (38). Therefore, the interaction between HHIP and GSTP1 in the cellular mitochondrial fraction suggests that HHIP may reduce oxidative stress by binding to and possibly increasing the activity of GSTP1.…”

Section: Hhip Interacts With Gstp1 and Enhances Glutathione-conjugatingmentioning

confidence: 99%

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Lao

Jiang

Yun

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip+/−), we observed increased lung compliance and spontaneous emphysema in Hhip+/− mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip+/− vs. Hhip+/+ mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip+/− mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip+/− mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip+/− mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

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Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism

Cited by 26 publications

References 50 publications

Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure

Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: In vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure

A Novel Method to Efficiently Highlight Nonlinearly Expressed Genes

Hhip haploinsufficiency sensitizes mice to age-related emphysema

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