NADPH:Quinone Oxidoreductase 1 Regulates Host Susceptibility to Ozone via Isoprostane Generation

Kummarapurugu, Apparao B.; Fischer, Bernard M.; Zheng, Shuo; Milne, Ginger L.; Ghio, Andrew J.; Potts-Kant, Erin N.; Foster, W. Michael; Soderblom, Erik J.; Dubois, Laura G.; Moseley, M. Arthur; Thompson, J. Will; Voynow, Judith A.

doi:10.1074/jbc.m112.438440

Cited by 7 publications

(3 citation statements)

References 47 publications

(63 reference statements)

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“… 46 , 47 This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase which reduces quinones to hydroquinones. Lower NQO1 activity caused by gene mutations has been associated with tardive dyskinesia, 48 an increased pulmonary susceptibility to ozone, 49 and susceptibility to various forms of cancer. 50 , 51 In addition, NQO1 binds and protects the tumor suppressor p53 against proteasomal degradation; thus, it has even broader cytoprotective roles, beyond its enzymatic functions.…”

Section: Review Of Genes and Results For Degenerative And Immunologicmentioning

confidence: 99%

The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

Gao¹,

Doan²,

Hybertson³

2014

CPAA

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Nuclear factor (erythroid-derived 2)-like 2 (Nrf2; encoded in humans by the NFE2L2 gene) is a transcription factor that regulates the gene expression of a wide variety of cytoprotective phase II detoxification and antioxidant enzymes through a promoter sequence known as the antioxidant-responsive element (ARE). The ARE is a promoter element found in many cytoprotective genes; therefore, Nrf2 plays a pivotal role in the ARE-driven cellular defense system against environmental stresses. Agents that target the ARE/Nrf2 pathway have been tested in a wide variety of disorders, with at least one new Nrf2-activating drug now approved by the US Food and Drug Administration. Examination of in vitro and in vivo experimental results, and taking into account recent human clinical trial results, has led to an opinion that Nrf2-activating strategies – which can include drugs, foods, dietary supplements, and exercise – are likely best targeted at disease prevention, disease recurrence prevention, or slowing of disease progression in early stage illnesses; they may also be useful as an interventional strategy. However, this rubric may be viewed even more conservatively in the pathophysiology of cancer. The activation of the Nrf2 pathway has been widely accepted as offering chemoprevention benefit, but it may be unhelpful or even harmful in the setting of established cancers. For example, Nrf2 activation might interfere with chemotherapies or radiotherapies or otherwise give tumor cells additional growth and survival advantages, unless they already possess mutations that fully activate their Nrf2 pathway constitutively. With all this in mind, the ARE/Nrf2 pathway remains of great interest as a possible target for the pharmacological control of degenerative and immunological diseases, both by activation and by inhibition, and its regulation remains a promising biological target for the development of new therapies.

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Section: Review Of Genes and Results For Degenerative And Immunologicmentioning

confidence: 99%

The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

Gao¹,

Doan²,

Hybertson³

2014

CPAA

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“…The protocol was approved by the Institutional Review Board for clinical investigations, Duke University Medical Center to use deidentified human lung donor airway tissue discarded during lung transplant procedure. Primary HBE cells were harvested and cultured as previously described ( 50 , 51 ). Briefly, human tracheobronchial tissues obtained from the Lung Transplant Program in the Department of Pathology at Duke University Medical Center were processed by proteolytic digestion (Protease Type XIV, Sigma).…”

Section: Methodsmentioning

confidence: 99%

Neutrophil elastase decreases SARS-CoV-2 spike protein binding to human bronchial epithelia by clipping ACE-2 ectodomain from the epithelial surface

Kummarapurugu¹,

Hawkridge²,

Ma³

et al. 2023

Journal of Biological Chemistry

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“…Gene polymorphisms for the phase-II xenobiotic metabolizing enzyme NQO1 have been allied to pulmonary and epithelial impairments in response to O 3 in the exercising subjects (Bergamaschi et al, 2001;Kummarapurugu et al, 2013). NQO1 Pro187Ser polymorphism was evaluated in a study on nitrogen dioxide and its effects on asthma, which showed a recessive effect for the 187 Pro/Pro genotype (Castro-Giener et al, 2009).To assess the functional significance and potential impact of this mutation on the structure of NQO1 protein, a bioinformatics based approach was pursued to perform the sequence and structural analysis of this protein.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

NQO1 rs1800566 polymorph is more prone to NOx induced lung injury: Endorsing deleterious functionality through informatics approach

Basharat

Messaoudi

Ruba

et al. 2016

Gene

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NADPH:Quinone Oxidoreductase 1 Regulates Host Susceptibility to Ozone via Isoprostane Generation

Cited by 7 publications

References 47 publications

The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders

Neutrophil elastase decreases SARS-CoV-2 spike protein binding to human bronchial epithelia by clipping ACE-2 ectodomain from the epithelial surface

NQO1 rs1800566 polymorph is more prone to NOx induced lung injury: Endorsing deleterious functionality through informatics approach

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