RGD Reference Report - Increased expression of NAD(P)H oxidase subunit p67(phox) in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension. - Rat Genome Database

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Increased expression of NAD(P)H oxidase subunit p67(phox) in the renal medulla contributes to excess oxidative stress and salt-sensitive hypertension.

Authors: Feng, D  Yang, C  Geurts, AM  Kurth, T  Liang, M  Lazar, J  Mattson, DL  O'connor, PM  Cowley AW, JR 
Citation: Feng D, etal., Cell Metab. 2012 Feb 8;15(2):201-8. doi: 10.1016/j.cmet.2012.01.003.
RGD ID: 9587793
Pubmed: PMID:22326221   (View Abstract at PubMed)
PMCID: PMC3280886   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cmet.2012.01.003   (Journal Full-text)

NAD(P)H oxidase has been shown to be important in the development of salt-sensitive hypertension. Here, we show that the expression of a subunit of NAD(P)H oxidase, p67(phox), was increased in response to a high-salt diet in the outer renal medulla of the Dahl salt-sensitive (SS) rat, an animal model for human salt-sensitive hypertension. The higher expression of p67(phox), not the other subunits observed, was associated with higher NAD(P)H oxidase activity and salt sensitivity in SS rats compared with a salt-resistant strain. Genetic mutations of the SS allele of p67(phox) were found in the promoter region and contributed to higher promoter activity than that of the salt-resistant strain. To verify the importance of p67(phox), we disrupted p67(phox) in SS rats using zinc-finger nucleases. These rats exhibited a significant reduction of salt-sensitive hypertension and renal medullary oxidative stress and injury. p67(phox) could represent a target for salt-sensitive hypertension therapy.



Disease Annotations    
proteinuria  (IMP,ISO)
renal fibrosis  (IMP,ISO)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Ncf2  (neutrophil cytosolic factor 2)
Ncf2em1Mcwi  (neutrophil cytosolic factor 2; zinc finger nuclease induced mutant 1,Mcwi)

Genes (Mus musculus)
Ncf2  (neutrophil cytosolic factor 2)

Genes (Homo sapiens)
NCF2  (neutrophil cytosolic factor 2)

Strains
SS-Ncf2em1Mcwi-/-  (SS-Ncf2em1Mcwi-/Ncf2em1Mcwi-)
SS-Ncf2em1Mcwi  (NA)

Objects referenced in this article
Strain SS-Ncf2em1Mcwi+/+ SS-Ncf2em1Mcwi+/Ncf2em1Mcwi+ Rattus norvegicus

Additional Information