RGD Reference Report - Role of NAD(P)H:quinone oxidoreductase in the progression of neuronal cell death in vitro and following cerebral ischaemia in vivo. - Rat Genome Database

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Role of NAD(P)H:quinone oxidoreductase in the progression of neuronal cell death in vitro and following cerebral ischaemia in vivo.

Authors: Kapinya, KJ  Harms, U  Harms, C  Blei, K  Katchanov, J  Dirnagl, U  Hortnagl, H 
Citation: Kapinya KJ, etal., J Neurochem 2003 Mar;84(5):1028-39.
RGD ID: 727509
Pubmed: PMID:12603827   (View Abstract at PubMed)

A direct involvement of the antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in neuroprotection has not yet been shown. The aim of this study was to examine changes, localization and role of NQO1 after different neuronal injury paradigms. In primary cultures of rat cortex the activity of NQO1 was measured after treatment with ethylcholine aziridinium (AF64A; 40 micro m), inducing mainly apoptotic cell death, or oxygen-glucose deprivation (OGD; 120 min), which combines features of apoptotic and necrotic cell death. After treatment with AF64A a significant NQO1 activation started after 24 h. Sixty minutes after OGD a significant early induction of the enzyme was observed, followed by a second increase 24 h later. Enzyme activity was preferentially localized in glial cells in control and injured cultures, however, expression also occurred in injured neuronal cells. Inhibition of the NQO1 activity by dicoumarol, cibacron blue or chrysin (1-100 nM) protected the cells both after exposure to AF64A or OGD as assessed by the decreased release of lactate dehydrogenase. Comparable results were obtained in vivo using a mouse model of focal cerebral ischaemia. Dicoumarol treatment (30 nmol intracerebroventricular) reduced the infarct volume by 29% (p = 0.005) 48 h after the insult. After chemical induction of NQO1 activity by t-butylhydroquinone in vitro neuronal damage was exaggerated. Our data suggest that the activity of NQO1 is a deteriorating rather than a protective factor in neuronal cell death.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Nqo1Ratpositive regulation of neuron apoptotic process  IMP  RGD 

Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Nqo1RatNAD(P)H dehydrogenase (quinone) activity  IDA  RGD 

RGD Manual Annotations


  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
NQO1Humanoxidative stress response pathway  ISONqo1 (Rattus norvegicus) RGD 
Nqo1Ratoxidative stress response pathway  IDA  RGD 
Nqo1Mouseoxidative stress response pathway  ISONqo1 (Rattus norvegicus) RGD 

Genes (Rattus norvegicus)
Nqo1  (NAD(P)H quinone dehydrogenase 1)

Genes (Mus musculus)
Nqo1  (NAD(P)H dehydrogenase, quinone 1)

Genes (Homo sapiens)
NQO1  (NAD(P)H quinone dehydrogenase 1)