RGD Reference Report - Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury. - Rat Genome Database

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Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury.

Authors: Ishihara, M  Urushido, M  Hamada, K  Matsumoto, T  Shimamura, Y  Ogata, K  Inoue, K  Taniguchi, Y  Horino, T  Fujieda, M  Fujimoto, S  Terada, Y 
Citation: Ishihara M, etal., Am J Physiol Renal Physiol. 2013 Aug 15;305(4):F495-509. doi: 10.1152/ajprenal.00642.2012. Epub 2013 May 22.
RGD ID: 11561968
Pubmed: PMID:23698117   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00642.2012   (Journal Full-text)

Autophagy is a cellular recycling process induced in response to many types of stress. However, little is known of the signaling pathways that regulate autophagy during acute kidney injury (AKI). Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP)3 and sestrin-2 are the target proteins of hypoxia-inducible factor (HIF)-1alpha and p53, respectively. The aim of this study was to investigate the roles of BNIP3 and sestrin-2 in oxidative stress-induced autophagy during AKI. We used rat ischemia-reperfusion injury and cultured renal tubular (NRK-52E) cells as in vivo and in vitro models of AKI, respectively. Renal ischemia-reperfusion injury upregulated the expression of BNIP3 and sestrin-2 in the proximal tubules, as measured by immunohistochemical staining and Western blot analysis. In vitro, NRK-52E cells exposed to hypoxia showed increased expression of BNIP3 mRNA and protein in a HIF-1alpha-dependent manner. In contrast, sestrin-2 mRNA and protein expression were upregulated in a p53-dependent manner after exposure to oxidative stress (exogenous H2O2). NRK-52E cells stably transfected with a fusion protein between green fluorescent protein and light chain 3 were used to investigate autophagy. Overexpression of BNIP3 or sestrin-2 in these cells induced light chain 3 expression and formation of autophagosomes. Interestingly, BNIP3-induced autophagosomes were mainly localized to the mitochondria, suggesting that this protein selectively induces mitophagy. These observations demonstrate that autophagy is induced in renal tubules by at least two independent pathways involving p53-sestrin-2 and HIF-1alpha-BNIP3, which may be activated by different types of stress to protect the renal tubules during AKI.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BNIP3HumanKidney Reperfusion Injury  ISOBnip3 (Rattus norvegicus)mRNA and protein:increased expression:kidneyRGD 
Bnip3RatKidney Reperfusion Injury  IEP mRNA and protein:increased expression:kidneyRGD 
Bnip3MouseKidney Reperfusion Injury  ISOBnip3 (Rattus norvegicus)mRNA and protein:increased expression:kidneyRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bnip3Ratpositive regulation of autophagy of mitochondrion  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bnip3  (BCL2 interacting protein 3)

Genes (Mus musculus)
Bnip3  (BCL2/adenovirus E1B interacting protein 3)

Genes (Homo sapiens)
BNIP3  (BCL2 interacting protein 3)


Additional Information