Opposing effects of nasal epithelial NAD(P)H dehydrogenase quinine 1 and heme oxygenase 1 expression on upper and lower airway symptoms in adolescents with asthma

Noel, Sanjeev; Saams, J.N.; Ong, Mary Jane; Breysse, Patrick N.; Diette, Gregory B.; Biswal, Shyam; Matsui, Elizabeth C.

doi:10.1016/j.jaci.2011.03.029

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Although it will be difficult to predict from this study how this inverse HO-1 expression may affect patients with septic shock, these findings may be important because NRF2-regulated HO-1 gene expression has been shown to protect against experimental sepsis by upregulating IL-10 and IL-1 levels and increasing mitochondrial biogenesis (19, 20). Furthermore, in a recent study, Noel et al (21) found significant opposing effects of NQO1 and HO-1 mRNA levels on asthma symptoms in humans. A higher NQO1 expression correlated with worse asthma symptoms, whereas the reverse was true for HO-1 expression.…”

Section: Discussionmentioning

confidence: 96%

The Effect of Ex Vivo CDDO-Me Activation on Nuclear Factor Erythroid 2–Related Factor 2 Pathway in White Blood Cells From Patients With Septic Shock

Noel¹,

Zheng

Navas‐Acien

et al. 2014

Shock

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Nuclear factor erythroid 2–related factor 2 (NRF2) has been shown to protect against experimental sepsis in mice and lipopolysaccharide (LPS)-induced inflammation in ex vivo white blood cells from healthy subjects by upregulating cellular antioxidant genes. The objective of this study was to test the hypothesis that ex vivo methyl 2-cyano-3, 12-dioxoolean-1,9-dien-28-oate (CDDO-Me) activates NRF2-regulated antioxidant genes in white blood cells from patients with septic shock and protects against LPS-induced inflammation and reactive oxidative species production. Peripheral blood was collected from 18 patients with septic shock who were being treated in medical and surgical intensive care units. Real-time polymerase chain reaction was used to quantify the expression of NRF2 target genes (NQO1, HO-1, GCLM, and FTL) and IL-6 in peripheral blood mononuclear cells (PBMCs), monocytes, and neutrophils after CDDO-Me treatment alone or after subsequent LPS exposure. Superoxide anion (O2−) was measured to assess the effect of CDDO-Me pretreatment on subsequent LPS exposure. Treatment with CDDO-Me increased the gene expression of NQO1 (P = 0.04) and decreased the expression of HO-1 (P = 0.03) in PBMCs from patients with septic shock. Purified monocytes exhibited significant increases in the expression of NQO1 (P = 0.01) and GCLM (P = 0.003) after CDDO-Me treatment. Levels of other NRF2 target genes (HO-1 and FTL) remained similar to those of vehicle-treated cells. Peripheral blood mononuclear cells showed a trend toward increased IL-6 gene expression after CDDO-Me treatment, whereas purified monocytes showed a trend toward decreased IL-6. There was no discernible trend in the IL-6 expression subsequent to LPS treatment in either vehicle-treated or CDDO-Me–treated PBMCs and monocytes. Treatment with CDDO-Me significantly increased O2− production in PBMCs (P = 0.04). Although CDDO-Me pretreatment significantly attenuated O2− production to subsequent LPS exposure (P = 0.03), the change was comparable to that observed in vehicle-treated PBMCs. Pretreatment with CDDO-Me followed by LPS exposure had no significant effect on O2− levels in purified monocytes. These data suggest that the NRF2 pathway is differentially responsive to CDDO-Me activation in peripheral blood cells from patients with septic shock and results in increased O2− production. The data may also suggest a suppressed NRF2 pathway in white blood cells from critically ill patients.

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Section: Discussionmentioning

confidence: 96%

The Effect of Ex Vivo CDDO-Me Activation on Nuclear Factor Erythroid 2–Related Factor 2 Pathway in White Blood Cells From Patients With Septic Shock

Noel¹,

Zheng

Navas‐Acien

et al. 2014

Shock

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“…According to Yeligar et al, livers of ethanol‐fed c‐Jun fl/fl mice showed attenuated mRNA levels of HO‐1 , but not NQO1 , supporting the role of c‐Jun in ethanol‐induced HO‐1 expression; in vitro and in vivo results provided evidence that ethanol‐induced oxidative stress differentially regulated the expression of HO‐1 and NQO1 in liver cells 23 . Furthermore, NQO1 and HO‐1 expression in nasal epithelium are inversely correlated indicating that non‐NRF2 mechanisms might play an important role in regulation of these genes; thus, the opposing relationships of NQO1 and HO‐1 with upper and lower airways symptoms suggest that induction of phase II enzymes could result in pleiotropic clinical effects 24 . The major characteristics of Nrf2 are to some extent mimicked by Nrf2‐dependent genes and their proteins including HO‐1, which exerts beneficial effects through the protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis 25 .…”

Section: Discussionmentioning

confidence: 98%

“…23 Furthermore, NQO1 and HO-1 expression in nasal epithelium are inversely correlated indicating that non-NRF2 mechanisms might play an important role in regulation of these genes; thus, the opposing relationships of NQO1 and HO-1 with upper and lower airways symptoms suggest that induction of phase II enzymes could result in pleiotropic clinical effects. 24 The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including HO-1, which exerts beneficial effects through the protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis. 25 Another study reported by Ge et al showed that overexpression of Brahma-related gene 1 (Brg1) in AML12 cells selectively enhanced HO-1 gene expression after hypoxia/reoxygenation treatment but did not affect the other Nrf2 target gene NQO1; furthermore, chromatin immunoprecipitation analysis revealed that Brg1 overexpression could significantly increase the recruitment of Brg1 protein to HO-1 but not NQO1 promoter.…”

Section: Discussionmentioning

confidence: 99%

The vicious circle of UHRF1 down‐regulation and KEAP1/NRF2/HO‐1 pathway impairment promotes oxidative stress‐induced endothelial cell apoptosis in diabetes

et al. 2022

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Background Oxidative stress is recognized as a key factor in the induction of endothelial dysfunction in diabetes. However, the specific mechanisms have not been fully elucidated. We herein hypothesized that ubiquitin‐like containing PHD and RING finger domains 1 (UHRF1) might have a role in oxidative stress‐induced endothelial cell (EC) apoptosis in diabetes. Methods Western blot, qPCR, wound healing assay, apoptosis assay, reactive oxygen species (ROS) detection, dual‐luciferase reporter assay, methylation‐specific PCR, bisulfite sequencing PCR and chromatin immunoprecipitation assay were performed. Results UHRF1 expression levels were significantly decreased in endothelial colony‐forming cells derived from peripheral blood of participants with type 2 diabetes compared with individuals without diabetes. ECs treated with high glucose, palmitate or hydrogen peroxide in vitro also exhibited decreased UHRF1 protein levels. Silencing of UHRF1 led to decreased migration ability and increased apoptosis and ROS production in ECs, which might be related to impaired Kelch‐like ECH‐associated protein 1 (KEAP1)/nuclear factor erythroid 2‐related factor 2 (NRF2)/haeme oxygenase‐1 pathway. Mechanistically, UHRF1 is closely implicated in epigenetic regulation of chromatin modification status at KEAP1 genomic locus via histone acetylation. NRF2 down‐regulation in turn inhibits UHRF1 protein level, which might be due to increased ROS generation. Conclusion Diabetes‐induced oxidative stress can mediate down‐regulation of UHRF1, which enhances ROS production by regulating KEAP1/p‐NRF2 pathway through histone acetylation and might also form a self‐perpetuating feedback loop with KEAP1/p‐NRF2 to further promote oxidative stress‐induced apoptosis of ECs in diabetes.

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“…In contrast, HO-1 expression was reduced in airway smooth muscle cells (ASMCs) from patients with mild and severe asthma [3]. In adolescents with asthma, an inverse relationship was detected between airway epithelial HO-1 expression and disease severity, thereby supporting a protective role of HO-1 against asthma symptoms [4].…”

Section: Introductionmentioning

confidence: 99%

Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma

et al. 2015

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Opposing effects of nasal epithelial NAD(P)H dehydrogenase quinine 1 and heme oxygenase 1 expression on upper and lower airway symptoms in adolescents with asthma

Cited by 6 publications

References 11 publications

The Effect of Ex Vivo CDDO-Me Activation on Nuclear Factor Erythroid 2–Related Factor 2 Pathway in White Blood Cells From Patients With Septic Shock

The Effect of Ex Vivo CDDO-Me Activation on Nuclear Factor Erythroid 2–Related Factor 2 Pathway in White Blood Cells From Patients With Septic Shock

The vicious circle of UHRF1 down‐regulation and KEAP1/NRF2/HO‐1 pathway impairment promotes oxidative stress‐induced endothelial cell apoptosis in diabetes

Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma

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