RGD Reference Report - Hydrogen peroxide induces lysosomal protease alterations in PC12 cells. - Rat Genome Database

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Hydrogen peroxide induces lysosomal protease alterations in PC12 cells.

Authors: Lee, DC  Mason, CW  Goodman, CB  Holder, MS  Kirksey, OW  Womble, TA  Severs, WB  Palm, DE 
Citation: Lee DC, etal., Neurochem Res. 2007 Sep;32(9):1499-510. Epub 2007 Apr 18.
RGD ID: 2306497
Pubmed: PMID:17440810   (View Abstract at PubMed)
DOI: DOI:10.1007/s11064-007-9338-5   (Journal Full-text)

Alterations in lysosomal proteases have been implicated in many neurodegenerative diseases. The current study demonstrates a concentration-dependent decrease in PC12 cell viability and transient changes in cystatin C (CYSC), cathepsin B (CATB), cathepsin D (CATD) and caspase-3 following exposure to H2O2. Furthermore, activation of CATD occurred following exposure to H2O2 and cysteine protease suppression, while inhibition of CATD with pepstatin A significantly improved cell viability. Additionally, significant PARP cleavage, suggestive of caspase-3-like activity, was observed following H2O2 exposure, while inhibition of caspase-3 significantly increased cell viability compared to H2O2 administration alone. Collectively, our data suggest that H2O2 induced cell death is regulated at least in part by caspase-3 and CATD. Furthermore, cysteine protease suppression increases CATD expression and activity. These studies provide insight for alternate pathways and potential therapeutic targets of cell death associated with oxidative stress and lysosomal protease alterations.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to hydrogen peroxide  IEP 2306497 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cst3  (cystatin C)


Additional Information