RGD Reference Report - Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study. - Rat Genome Database

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Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study.

Authors: Joshi, S  Saylor, BT  Wang, W  Peck, AB  Khan, SR 
Citation: Joshi S, etal., PLoS One. 2012;7(10):e47738. doi: 10.1371/journal.pone.0047738. Epub 2012 Oct 16.
RGD ID: 10040961
Pubmed: PMID:23091645   (View Abstract at PubMed)
PMCID: PMC3473023   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0047738   (Journal Full-text)

PURPOSE: We have previously shown that production of reactive oxygen species (ROS) is an important contributor to renal injury and inflammation following exposure to oxalate (Ox) or calcium-oxalate (CaOx) crystals. The present study was conducted, utilizing global transcriptome analyses, to determine the effect of Apocynin on changes in the NADPH oxidase system activated in kidneys of rats fed a diet leading to hyperoxaluria and CaOx crystal deposition. APPROACH: Age-, sex- and weight-matched rats were either fed regular rat chow or regular rat chow supplemented with 5% w/w hydroxy-L-proline (HLP). Half of the rats on the HLP diet were also placed on Apocynin-supplemented H(2)O. After 28 days, each rat was euthanized, their kidneys freshly explanted and dissected to obtain both cortex and medulla tissues. Total RNA was extracted from each tissue and subjected to genomic microarrays to obtain global transcriptome data. KEGG was used to identify gene clusters with differentially expressed genes. Immunohistochemistry was used to confirm protein expressions of selected genes. RESULTS: Genes encoding both membrane- and cytosolic-NADPH oxidase complex-associated proteins, together with p21rac and Rap1a, were coordinately up-regulated significantly in both renal medulla and cortex tissues in the HLP-fed rats compared to normal healthy untreated controls. Activation of NADPH oxidase appears to occur via the angiotensin-II/angiotensin-II receptor-2 pathway, although the DAG-PKC pathway of neutrophils may also contribute. Immuno histochemical staining confirmed up-regulated gene expressions. Simultaneously, genes encoding ROS scavenger proteins were down-regulated. HLP-fed rats receiving Apocynin had a complete reversal in the differential-expression of the NADPH oxidase system genes, despite showing similar levels of hyperoxaluria. CONCLUSIONS: A strong up-regulation of an oxidative/respiratory burst involving the NADPH oxidase system, activated via the angiotensin-II and most likely the DAG-PKC pathways, occurs in kidneys of hyperoxaluric rats. Apocynin treatment reversed this activation without affecting the levels of hyperoxaluria.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperoxaluria  ISORap1a (Rattus norvegicus)10040961; 10040961mRNA:increased expression:kidney (rat)RGD 
Hyperoxaluria  IEP 10040961mRNA:increased expression:kidney (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rap1a  (RAP1A, member of RAS oncogene family)

Genes (Mus musculus)
Rap1a  (RAS-related protein 1a)

Genes (Homo sapiens)
RAP1A  (RAP1A, member of RAS oncogene family)


Additional Information