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)

Tissue reoxygenation following hypoxia is associated with ischemia-reperfusion injury (IRI) and may signal the development of ischemic preconditioning, an adaptive state that is protective against subsequent IRI. Here we used microarray RNA analysis of in vivo and in vitro models of IRI to delineate the underlying molecular mechanisms. Microarray analysis of renal tissue after ischemia-reperfusion revealed a number of highly up-regulated antioxidant genes including aldehyde dehydrogenases (ALDH1A1 and ALDH1A7), glutathione S-transferases (GSTM5, GSTA2 and GSTP1), and NAD(P)H quinone oxidoreductase (NQO1). The transcription factor NF-E2-related factor-2 (Nrf2), a master regulator of this antioxidant response, is also elevated in IRI. Furthermore, microarray analysis of renal epithelial cells exposed to hypoxia/reoxygenation identified Nrf2 to be up-regulated on reoxygenation. We also reveal a reoxygenation-specific nuclear accumulation of Nrf2 protein and subsequent activation of a NQO1 promoter reporter construct. Attenuating reactive oxygen species (ROS) in reoxygenation using the antioxidant N-acetyl cysteine results in inhibition of Nrf-2 activation. mRNA levels for Nrf2-dependent genes were detected in human liver biopsy 1 h after transplantation. These results indicate that reoxygenation-dependent Nrf-2 activity facilitates ischemic preconditioning through the induction of antioxidant gene expression and that ROS may be critical in signaling this event.
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PMID:Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury. 1714 1

The antioxidant defense system protects DNA from the damaging effects of oxidative stress and is hypothesized to be associated with an increased risk of male infertility. Polymorphisms in antioxidant genes and the gene-gene interactions associated with the antioxidant system may increase the potential risk of male infertility. In the present case-controlled study, the individual link between seven gene polymorphisms (NQO1 rs1800566, SOD2 rs4880, GSTM3 rs1571858, rs3814309, rs7483, GSTM5 rs11807 and GSTP1 rs1695) and the risk of male infertility was investigated. A total of 248 idiopathic infertility patients and 310 fertile controls were selected, and genotyping was performed using the Mass ARRAY platform. There were no significant associations between the seven polymorphisms and risk of male infertility. However, the analysis of gene-gene interactions showed a decreased risk of male infertility in GSTM3 rs3814309/NQO1 rs1800566 [CC x CT/TT; odds ratio (OR)=0.56, 95% confidence interval (CI)=0.34-0.92; P=0.022), and a significant association between a gene-gene interaction in GSTM3 rs1571858/NQO1 rs1800566 and azoospermia (AG/GG x CC; OR=3.84, 95% CI=1.25-11.81; P=0.019).
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PMID:Association of single-nucleotide polymorphisms in antioxidant genes and their gene-gene interactions with risk of male infertility in a Chinese population. 3249 61