RGD Reference Report - Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage. - Rat Genome Database

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Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage.

Authors: Tabuchi, K  Pak, K  Chavez, E  Ryan, AF 
Citation: Tabuchi K, etal., Neuroscience. 2007 Oct 12;149(1):213-22. Epub 2007 Aug 2.
RGD ID: 2314390
Pubmed: PMID:17869439   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2007.06.061   (Journal Full-text)

Apoptotic cell death is considered to play a key role in gentamicin-induced cochlear hair cell loss. Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptosis that can prevent activation of effector caspases. This study was designed to investigate the possible involvement of X-linked inhibitor of apoptosis protein (XIAP) in hair cell death due to gentamicin. Basal turn organ of Corti explants from postnatal day (p) p3 or p4 rats were maintained in tissue culture and were exposed to 35 muM gentamicin for up to 48 h. Effects of specific XIAP inhibitors on gentamicin-induced hair cell loss and caspase-3 activation were examined. XIAP inhibitors increased gentamicin-induced hair cell loss but an inactive analog had no effect. Caspase-3 activation was primarily observed at 36 or 48 h in gentamicin-treated hair cells, whereas caspase-3 activation peaked at 24-36 h when explants were treated with gentamicin and an XIAP inhibitor. The inhibitors alone had no effect on hair cells. Finally, a caspase-3 inhibitor decreased caspase-3 activation and hair cell loss induced by gentamicin and an XIAP inhibitor, but caspase-8 and -9 inhibitors did not. The results indicate that XIAP normally acts to decrease caspase-3 activation and hair cell loss during gentamicin ototoxicity, as part of a protective response to potentially damaging stimuli.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IMP 2314390 RGD 
positive regulation of apoptotic process  IMP 2314390; 2314390 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)
Casp9  (caspase 9)
Xiap  (X-linked inhibitor of apoptosis)

Genes (Mus musculus)
Casp3  (caspase 3)
Casp9  (caspase 9)
Xiap  (X-linked inhibitor of apoptosis)

Genes (Homo sapiens)
CASP3  (caspase 3)
CASP9  (caspase 9)
XIAP  (X-linked inhibitor of apoptosis)


Additional Information