Polymorphisms of NRF2 gene correlated with decreased FEV1 in lung cancers of smokers

Sasaki, Hidefumi; Suzuki, Ayumi; Shitara, Masayuki; Hikosaka, Yu; Okuda, Kunio; Moriyama, Satoru; Yano, Motoki; Fujii, Yoshitaka

doi:10.3892/br.2013.83

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…Using an additive model, a significant interaction was identified between rs6726395 (G/G + G/A) genotyped individuals, smoking status and reduced mean FEV 1 in the same Japanese cohort ( p int = 0.010) [23,24]. Similarly, the intronic haplotype rs2364723 C/rs6726395 A was associated with significantly reduced FEV 1 in Japanese smokers with lung cancer [25], supporting work by Siedlinski et al . [26] who found lower FEV 1 levels in the Dutch Vlagtwedde-Vlaardingen cohort of 1152 individuals (p = 0.04; CI −87.3 to −1.7).…”

Section: Genetic Mutations Of Nrf2 and Association With Disease Risksupporting

confidence: 64%

Functional polymorphisms in Nrf2: implications for human disease

Cho

Marzec

Kleeberger

2015

Free Radical Biology and Medicine

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Nuclear factor (erythroid derived)-2 like 2 (NFE2L2), also known as nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), is a ubiquitous transcription factor essential for protecting cells and tissues from oxidative stress-induced injury. Positional cloning and studies with Nrf2 knockout mice have identified important roles for this transcription factor in disease phenotypes for many organ systems. Studies have also characterized the means through which human Nrf2 is regulated and the mechanisms of interaction with antioxidant response elements (ARE) in promoters of effector genes. Moreover, single nucleotide polymorphisms (SNPs) in Nrf2 have been identified and evaluated for effects on gene expression and function, and translational investigations have sought to determine whether loss of function SNPs associate with disease progression. In this review, we present 1) an overview of the human Nrf2 gene and protein domain, 2) identification of genetic mutations in Nrf2 and associations of the mutations with multiple diseases, and 3) the role of somatic mutations in Nrf2 in diseases, primarily various cancers.

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Section: Genetic Mutations Of Nrf2 and Association With Disease Risksupporting

confidence: 64%

Functional polymorphisms in Nrf2: implications for human disease

Cho

Marzec

Kleeberger

2015

Free Radical Biology and Medicine

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“…The Nrf2 pathway is an anti-apoptotic pathway that has been demonstrate do function in many organs, particularly in the central nervous system (5). With a short half-life, Nrf2 is an important factor.…”

Section: Discussionmentioning

confidence: 99%

“…The Nrf2 pathway is anti-apoptotic and has multiple functions, including resistance to oxidative stress, regulation of inflammatory injury and relief from calcium overloading ( 4 ). Research findings indicate that Nrf2 regulates downstream molecules to protect nerves, particularly against apoptosis ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Curcumin attenuates hypoxic-ischemic brain injury in neonatal rats through induction of nuclear factor erythroid-2-related factor 2 and heme oxygenase-1

Cui

Song

Shi

2017

Experimental and Therapeutic Medicine

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Curcumin has previously demonstrated anti-inflammatory, anti-infective and immuno-suppressive effects. In the present study, whether the attenuating effects of curcumin against hypoxic-ischemic brain injury in neonatal rats are mediated via nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was investigated. A model of hypoxic-ischemic brain injury was created using 1-week-old Sprague Dawley rats (weight, 52±1 g). The model rats were treated with 150 mg/kg curcumin by gavage for 3 days. Malondialdehyde levels, and superoxide dismutase and caspase-3 activities were assayed using commercial kits and western blot analysis was used to measure inducible nitric oxide synthase (iNOS), Nrf2 and HO-1 expression levels. Treatment with curcumin effectively reduced the brain injury score, increased myelin basic protein (MBP) expression and increased the quantity of neuronal cells in neonatal rats with hypoxic-ischemic brain injury. Furthermore, treatment with curcumin significantly attenuated the changes in SOD activity and MDA levels and suppressed the iNOS protein expression induced in neonatal rats by hypoxic-ischemic brain injury. Treatment with curcumin significantly increased Nrf2 and HO-1 expression in the neonatal rats with hypoxic-ischemic brain injury. The present study indicated that curcumin attenuates hypoxic-ischemic brain injury in neonatal rats through the induction of Nrf2 and HO-1.

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“…Impaired Nrf2 expression in COPD patients might fail to evoke an appropriate antioxidant response and allow excessive apoptosis resulting in lung tissue destruction and emphysema. A previous cohort study showed that certain polymorphisms of the Nrf2 gene correlated with accelerated limitations in airflow of smokers [ 15 , 16 ]. Subjects with impaired Nrf2 might be related to COPD.…”

Section: Discussionmentioning

confidence: 99%

Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking

et al. 2016

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BackgroundCigarette smoking-induced oxidative stress is known to be a key mechanism in COPD pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central transcription factor that regulates the antioxidant defense system. The aim of this study was to compare Nrf2 expression in COPD subjects and control subjects, and to determine the role of Nrf2 in protecting against oxidative stress-induced apoptosis.MethodsWe enrolled 8 COPD subjects and 7 control subjects in this study. We performed bronchial brushing by bronchoscopy and obtained bronchial epithelial cells from the airways. Nrf2 expression in bronchial epithelial cells was evaluated by real-time PCR and Western blotting. We examined the effect of 10 or 15 % cigarette smoke extract (CSE) induced A549 cells apoptosis using a time-lapse cell imaging assay with caspase-3/7 activation detecting reagent and performed Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling assay for confirming A549 cells apoptosis. We also examined the effects of Nrf2 knockdown and, 0.1, 0.5, and 1.0 mM N-acetyl cysteine on CSE-induced apoptosis. Statistical analyses were performed using t-test, paired t-test or an analysis of variance followed by the Tukey-Kramer method.ResultsNrf2 mRNA expression in COPD subjects was significantly lower than that in control subjects and Nrf2 mRNA were negatively correlated with pack year. Nrf2 protein in COPD subjects was significantly lower than that in control subjects. CSE-induced A549 cells apoptosis was increased in a time-, concentration-dependent manner, and was significantly increased by Nrf2 knockdown. N-acetyl cysteine significantly ameliorated CSE-induced apoptosis.ConclusionsNrf2 expression was lower in COPD patients than in control subjects. Nrf2 might have a protective role against apoptosis caused by CSE-induced oxidative stress. These results suggest an involvement of Nrf2 in COPD and administration of antioxidants to patients with COPD might be a basic therapeutic option.

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Polymorphisms of NRF2 gene correlated with decreased FEV1 in lung cancers of smokers

Cited by 7 publications

References 31 publications

Functional polymorphisms in Nrf2: implications for human disease

Functional polymorphisms in Nrf2: implications for human disease

Curcumin attenuates hypoxic-ischemic brain injury in neonatal rats through induction of nuclear factor erythroid-2-related factor 2 and heme oxygenase-1

Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking

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