RGD Reference Report - Loss of calpain 10 causes mitochondrial dysfunction during chronic hyperglycemia. - Rat Genome Database

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Loss of calpain 10 causes mitochondrial dysfunction during chronic hyperglycemia.

Authors: Smith, MA  Covington, MD  Schnellmann, RG 
Citation: Smith MA, etal., Arch Biochem Biophys. 2012 Jul 15;523(2):161-8. doi: 10.1016/j.abb.2012.04.020. Epub 2012 May 1.
RGD ID: 7247732
Pubmed: PMID:22568896   (View Abstract at PubMed)
PMCID: PMC3874586   (View Article at PubMed Central)
DOI: DOI:10.1016/j.abb.2012.04.020   (Journal Full-text)

We showed that renal calpain 10, a mitochondrial and cytosolic Ca(2+)-regulated cysteine protease, is specifically decreased in kidneys of diabetic rats and mice, and is associated with diabetic nephropathy. The goals of this study were to examine renal calpain 10 and mitochondrial dysfunction in streptozotocin-induced hyperglycemic rats and determine the effects of siRNA-mediated knock down of renal calpain 10 on mitochondrial function. Four weeks after streptozotocin injection, calpain 10 protein and mRNA were decreased and calpain 10 substrates accumulated. We detected increased state 2 respiration in isolated renal mitochondria and increased markers of mitochondrial fission and mitophagy. All changes were prevented by daily insulin injection. Compared to scrambled siRNA, calpain 10 siRNA resulted in a marked decrease in renal calpain 10 at 2, 5 and 7 days. In concert with the loss of renal calpain 10, calpain 10 substrates accumulated, mitochondrial fusion decreased, mitochondrial fission and mitophagy increased. In summary, insulin-sensitive hyperglycemia induced loss of renal calpain 10 is correlated with renal mitochondrial dysfunction, fission and mitophagy, and specific depletion of renal calpain 10 produces similar mitochondrial defects. These results provide evidence that diabetes-induced renal mitochondrial dysfunction and renal injury may directly result from the loss of renal calpain 10.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CAPN10HumanExperimental Diabetes Mellitus  ISOCapn10 (Rattus norvegicus)mRNA and protein:decreased expression:kidney cortexRGD 
Capn10RatExperimental Diabetes Mellitus  IEP mRNA and protein:decreased expression:kidney cortexRGD 
Capn10MouseExperimental Diabetes Mellitus  ISOCapn10 (Rattus norvegicus)mRNA and protein:decreased expression:kidney cortexRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Capn10Ratautophagy of mitochondrion  IMP  RGD 
Capn10Ratmitochondrion organization  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Capn10  (calpain 10)

Genes (Mus musculus)
Capn10  (calpain 10)

Genes (Homo sapiens)
CAPN10  (calpain 10)


Additional Information