Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heme oxygenase (HO)-1 and -2 produce carbon monoxide, which is suspected, as is nitric oxide (NO), to function as a neuronal messenger. We report on glucocorticoid-mediated modulation of HO-2 and NO synthase expression in brain and the differential response of the two proteins to corticosterone in different brain regions. Corticosterone treatment (40 mg/kg, 20 days) had opposing effects on HO-2 and NO synthase transcript levels: increasing the 1.3- and 1.9-kb HO-2 mRNAs and decreasing that of the brain-specific 10.5-kb NO synthase. Corticosterone did not uniformly affect HO-2 protein expression in all regions, but appeared to cause a universal reduction in NO synthase, e.g., HO-2 was decreased in hippocampus (CA1 and dentate gyrus), but not in cerebellum. In contrast, NADPH diaphorase staining was reduced in hippocampus and in molecular and granule layers of cerebellum (not detected in Purkinje cells). Striking deficits in neuronal morphology and number of diaphorase-staining neurons were observed in the lateral tegmental area, paraventricular nucleus, and frontal cortex; HO-2 expression was only selectively affected. In cerebellum, activity of NO synthase, but not that of HO, was reduced. Consistent with the possibility that carbon monoxide can generate cyclic GMP, the change in cyclic GMP level did not mirror the decrease in NO synthase. We suggest that glucocorticoid-mediated deficits in hippocampal functions may reflect their negative effect on messenger-generating systems.
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PMID:Corticosterone regulates heme oxygenase-2 and NO synthase transcription and protein expression in rat brain. 751 67

In the course of our studies on the local blood flow modulation in the NMRI-mouse placenta we have focussed on regulatory pathways involving recently appreciated gaseous messenger molecules nitric oxide (NO) and carbon monoxide (CO), which are generated by NO synthase (NOS) and heme oxygenase (HO)-2, respectively. The distribution of NOS was investigated by immunohistochemistry using an antiserum to the neuronal isoform (NOS-I) and by NADPH diaphorase (NADPHd) histochemistry, supplemented with procedures (permanganate and formaldehyde method) serving to enhance the specificity of the enzyme histochemical method for NOS visualization. HO-2 was demonstrated immunohistochemically. In addition, cyclic guanosine monophosphate (cGMP)-forming soluble guanylate cyclase (sGC) and dehydrogenases generating the NOS co-substrate NADPH were analysed either by immunohistochemistry or enzyme histochemistry. NOS-I immunostaining was observed in the intraplacental visceral yolk sac epithelial cells but not in the placenta and extraplacental visceral epithelial yolk sac cells. Co-localization of NOS-I immunolabeling and NOS-associated NADPHd was exclusively found in the intraplacental visceral epithelial cells, while NADPHd activity not associated to NOS was present in other placental and extraplacental cells additionally analysed for control reasons. HO-2 and sGC immunoreactivity could not be detected in the placenta including the intraplacental visceral epithelial cells but were expressed in several extraplacental cells. Dehydrogenases producing the NOS co-substrate NADPH were present in the intraplacental visceral epithelium as well as in other placental and extraplacental cells. Since the intraplacental visceral epithelial yolk sac layer closely accompanies large fetal blood vessels entering the placental labyrinth from the chorionic plate it may be assumed that NO, generated by the NADPH-consuming NOS-I in the intraplacental yolk sac epithelium, acts to regulate the blood flow by relaxing smooth muscle cells in the wall of these fetal vessels. The lack of immunoreactivity to the NO-effector molecule sGC may be due to methodological reasons. The absence of the HO-2/CO system suggests its insignificant role as a potential gas signaling pathway in the vascular smooth muscle system of the intraplacental visceral yolk sac of mice.
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PMID:Nitric oxide synthase I immunoreactivity and NOS-associated NADPHd histochemistry in the visceral epithelial cells of the intraplacental mouse yolk sac. 873 2

Heme oxygenase isozymes, HO-1 (also known as hsp32) and HO-2, are the source for the formation of the putative messenger molecule carbon monoxide (CO), reactive iron, and the in vitro antioxidant bilirubin. We have developed and characterized transgenic (Tg) mice that overexpress the stress protein in neurons in various brain regions. The Tg mice were generated by the use of rat HO-1 cDNA under the control of the neuron-specific enolase promoter. Except for a tendency to have an enlarged spleen, Tg mice did not show gross anatomical changes. Increase in HO-1 mRNA, which was demonstrated by northern blot analysis and in situ hybridization, was accompanied by an increase in neuronal HO-1 protein expression, shown by immunohistochemistry and western blotting, and an increase in HO activity. Expression of the transgene correlated with an attenuation of exploratory behavior and increased circling activity and coincided with enhanced neuronal NADPH diaphorase staining. Those changes were not accompanied by an increase in DNA damage or significant change in whole-brain NO synthase activity. The HO-1 Tg mice potentially represent a good model to examine the function of CO as a neuromodulator, iron as a gene regulator, and bile pigments as in vivo antioxidants.
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PMID:Neuronal overexpression of heme oxygenase-1 correlates with an attenuated exploratory behavior and causes an increase in neuronal NADPH diaphorase staining. 957 92

Heme oxygenase (HO)/carbon monoxide (CO) and nitric oxide synthase (NOS)/nitric oxide (NO) systems are involved in sensory information processing. The present study was undertaken to examine the distribution of HO-2 and NOS in the spinal trigeminal nucleus (STN) of the rat, using histochemistry and immunohistochemistry. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining was found that NADPH-d activity was more prominent in the nucleus caudalis (Vc) and the dorsomedial subdivision of the nucleus oralis (Vo) than in other spinal trigeminal regions. Immunohistochemistry for HO-2 revealed that HO-2 staining neurons distributed extensively, which intensity was higher in the rostral than caudal part of the STN. The colocalization of NADPH-d and HO-2 was mainly confined in the Vc. The expression and distribution of NADPH-d and HO-2 suggest that NO and CO are likely neurotransmitters and might function in the processing orofacial signal in the STN together.
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PMID:Distribution of heme oxygenase-2 and NADPH-diaphorase in the spinal trigeminal nucleus of the rat. 1982 Oct 77