Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two pentose phosphate pathway-related proteins, NF-E2-related factor 2 (Nrf2)/ NAD(P)H dehydrogenase (Quinone) 1 (NQO1) regulate the expression of glucose metabolism and antioxidant genes. We evaluated the prognostic significance of NRF2, NQO1 and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameter and their relationship with non-small cell lung cancer (NSCLC) histology. A total of 241 patients, who underwent surgical resection for NSCLC, were reviewed retrospectively. Preoperative 18F-FDG PET and immunohistochemical results of Nrf2 and NQO1 were evaluated. In SQCC, the maximum standardized uptake value (SUVmax) was significantly higher in NQO1-high than in NQO1-low expression (p=0.023). In adenocarcinoma, SUVmax was not correlated with NQO1 expression. Patients with a high NQO1 expression showed poor recurrence-free survival (RFS) and overall survival (OS) than patients with a low NQO1 expression in squamous cell carcinoma (SQCC) (p=0.002 and p=0.014, respectively). NQO1 expression was not associated with clinical outcome in adenocarcinoma. Nrf2 expression was not correlated with prognosis in two types of NSCLC. High SUVmax was associated with poor RFS (p=0.03) but is not related to poor OS (p=0.569) in SQCC. In multivariate analyses, NQO1 expression and SUVmax were not independent prognostic factors in SQCC. However, in multivariate analysis combining NQO1 and SUVmax values, both low SUVmax and low NQO1 was independent prognostic factor for RFS and OS (HR= 3.790, p = 0.033 and HR= 2.961, p = 0.045, respectively). In conclusion, both low SUVmax and low NQO1 was an independent prognostic factor in SQCC alone. The sample size was small but there was a positive correlation between NQO1 expression and SUVmax in SQCC.
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PMID:Association between 18F-FDG uptake in PET/CT, Nrf2, and NQO1 expression and their prognostic significance in non-small cell lung cancer. 3086 98

The molecular mechanisms whereby placental growth factor (PlGF) mediates its effects in nonproliferative diabetic retinopathy (DR) are unknown. To better understand the role of PlGF in DR, we used tandem mass tags (TMT)-labeled quantitative proteomics to human retinal endothelial cells (HRECs), treated anti-PlGF antibody, and PBS as a control. Functional annotation and pathway enrichments were performed, which suggested that the differentially expressed proteins (DEPs) were involved in key metabolic processes, protein binding, and membrane, pentose phosphate pathway (PPP) and adherens junction. We conducted integrated gene profiles of our previously published transcriptomic data to the TMT-labeled proteomics data. The results showed the sixty genes were found to be changed at the proteome level. The functional annotation conducted for the sixty proteins suggested that 58.3% of proteins were involved in PPP, 25% of proteins were in interleukin-12 singling and 16.7% of proteins were involved in glycolysis and gluconeogenesis pathway. Mass spectrometry results were validated by transendothelial electrical resistance measurement by an electrical cell-impedance sensing (ECIS) and western blot analysis of VE-cadherin, G6PD. These findings suggest that the PPP proteins and antioxidants may act as a downstream target of PlGF and may play a decisive role in HREC biological functions in DR. SIGNIFICANCE: PlGF (Placental growth factor) is known to play a pivotal role in pathological angiogenesis and inflammation by stimulating endothelial cell migration and by recruiting pericytes and inflammatory cells such as microglia and macrophages. Despite the well-defined pathophysiological roles of PlGF, the underlying molecular and cellular mechanisms are not completely understood, especially the exact relationships between biochemical events and molecular pathways regulated by PlGF, whose inhibition exhibits a protective role in DR. This study provides new insights into protein expression patterns and enables the identification of many attractive candidates for investigation of PPP pathway role in the activation of the antioxidant defense system in DR. Our findings suggest that the PPP proteins and antioxidants (PRDX6, HMOX1, NQO1 and YES1) may act as downstream targets of PlGF and may play a decisive role in HREC biological functions in DR.
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PMID:Placental growth factor regulates the pentose phosphate pathway and antioxidant defense systems in human retinal endothelial cells. 3205 40

As an alternative electron sink, chlororespiration, comprising the NAD(P)H dehydrogenase complex and plastid terminal plastoquinone oxidase, may play a significant role in sustaining the redox equilibrium between stroma and thylakoid membrane. This study identified a distinct role for chlororespiration in the marine angiosperm Zostera marina, whose oxygen-evolving complex (OEC) is prone to photo-inactivation as a result of its inherent susceptibility to excess irradiation. The strong connectivity between OEC peripheral proteins and key chlororespiratory enzymes, as demonstrated in the interaction network of differentially expressed genes, suggested that the recovery of photo-inactivated OEC was connected with chlororespiration. Chlorophyll fluorescence, transcriptome and Western blot data verified a new physiological role for chlororespiration to function as photoprotection and generate a proton gradient across the thylakoid membrane for the recovery of photo-inactivated OEC. Chlororespiration was only activated in darkness following excess irradiation exposure, which might be related to electron deficiency in the electron transport chain because of the continuous impairment of the OEC. The activation of chlororespiration in Z. marina was prone to proactivity, which was also supported by the further activation of the oxidative pentose-phosphate pathway synthesizing NADPH to meet the demand of chlororespiration during darkness. This phenomenon is distinct from the common assumption that chlororespiration is prone to consuming redundant reducing power during the short transition phase from light to dark.
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PMID:Chlororespiration Serves as Photoprotection for the Photo-Inactivated Oxygen-Evolving Complex in Zostera marina, a Marine Angiosperm. 3249 41

Activating mutations in the KEAP1-NRF2 pathway are found in approximately 25% of lung tumours, where the hijacking of NRF2's cytoprotective functions results in aggressive tumour growth, chemoresistance, and a poor prognosis for patients. There are currently no approved drugs which target aberrant NRF2 activation, which means that there is an urgent clinical need to target this orphan oncogenic pathway in human tumours. In this study, we used an isogenic pair of wild-type and Keap1 knockout cells to screen a range of chemotherapeutic and pathway targeted anti-cancer drugs in order to identify compounds which display enhanced toxicity towards cells with high levels of Nrf2 activity. Through this approach, complemented by validation across a panel of eight human cancer cells lines from a range of different tissues, we identified the DNA damaging agent mitomycin C to be significantly more toxic in cells with aberrant Nrf2 activation. Mechanistically, we found that the NRF2 target genes cytochrome P450 reductase, NQO1, and enzymes in the pentose phosphate pathway, are all responsible for the NRF2-dependent enhanced bioactivation of mitomycin C. As mitomycin C is already approved for clinical use, it represents as excellent drug repositioning candidate to target the currently untreatable NRF2 activation in human tumours.
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PMID:NRF2-dependent bioactivation of mitomycin C as a novel strategy to target KEAP1-NRF2 pathway activation in human cancer. 3313 92


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