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)

Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator of one defense mechanism against such havoc. Nrf2 regulates the inducible expression of a group of detoxication enzymes, such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that Nrf2 also controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system x(c)(-)) activity. The response to electrophilic and reactive oxygen species-producing agents was profoundly impaired in Nrf2-deficient cells. The lack of induction of system x(c)(-) activity resulted in the minimum level of intracellular glutathione, and Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2 regulates a wide-ranging metabolic response to oxidative stress.
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PMID:Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. 1082 56

Acupuncture has been used as a clinical treatment in Oriental medicine for various diseases including diabetes mellitus, one of the most common metabolic disorders in humans. In the present study, the effect of acupuncture on the expressions of neuronal nitric oxide synthase (nNOS) and nitric oxide synthase (NOS) in the dorsolateral periaqueductal gray (DL-PAG) area of rats with streptozotocin (STZ)-induced diabetes was investigated via nNOS immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry. Enhanced expression of nNOS and NOS was detected in the DL-PAG of rats with STZ-induced diabetes, and acupunctural treatment at Zusanli acupoint suppressed the diabetes-induced enhancement in the expression of nNOS and NOS. The present results demonstrate that acupuncture is effective in the modulation of the expression of nNOS and NOS in the DL-PAG under diabetic conditions.
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PMID:Acupuncture decreases nitric oxide synthase expression in periaqueductal gray area of rats with streptozotocin-induced diabetes. 1253 47

The mesencephalic dorsolateral periaqueductal gray (dlPAG) mediates different modalities of aversive behaviors including pain and nociception and is anatomically delineated from other columns of the PAG by its content of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). In many brain regions, neuronal NADPH-d is a nitric oxide (NO) synthase (NOS) and NO production mediates many nociceptive and aversive behavioral responses. The aim of this study was to determine how the noxious stimulant capsaicin affects intracellular dynamics in the dlPAG evidenced by Fos protein immunoreactivity (index of intracellular activation) and the NADPH-d reactivity. The basic hypothesis tested was that the effect of systemic capsaicin administration involved activation of the NO-producing machinery in the dlPAG. Compared to vehicle, capsaicin (50mg/kg, subcutaneous) significantly increased NADPH-d reactivity and Fos expression along the dlPAG neuraxis. However, less than one percent of the capsaicin-induced Fos activation occurred in NADPH-d-positive cells. This suggests that different intracellular mechanisms involving NO and activation of at least one other transmitter substance underlie the effects of capsaicin in the dlPAG. Although NADPH-d is a marker for constitutive NOS, only about two-thirds of the NADPH-d-positive neurons in the dlPAG were colocalized with neuronal NOS immunoreactive cells. This observation suggests that in contrast to other brain regions, neuronal NOS is unlikely to account for all NADPH-d activity in the dlPAG. Taken together, the present results show that the effect of capsaicin requires activation of at least one other transmitter and NADPH-d-dependent NO synthesis involving, but not limited to, the neuronal NOS isoform.
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PMID:Acute capsaicin injection increases nicotinamide adenine dinucleotide phosphate diaphorase staining independent of Fos activation in the rat dorsolateral periaqueductal gray. 1683 9