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Hydrogen Peroxide Induces Lysosomal Protease Alterations in PC12 Cells

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Abstract

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.

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Acknowlegdements

We would like to thank Mrs. Glory Brown, Mrs. Frances James, Mrs. Brenda Arnold, Mrs. Shalonda Fagg and Mrs. Pamela Bryant for editorial assistance. Supported by NIH/NIGMS/MBRS S06 GM 0811, NIH/NCRR/RCMI G12RR03020

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Authors and Affiliations

  1. College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA

    Daniel C. Lee, Ceceile W. Mason, Carl B. Goodman, Maurice S. Holder, Otis W. Kirksey, Tracy A. Womble & Donald E. Palm

  2. Pharmacology Department, College of Medicine, Pennsylvania State University, Hershey, PA, 17033, USA

    Walter B. Severs

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  1. Daniel C. Lee
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Correspondence to Donald E. Palm.

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Lee, D.C., Mason, C.W., Goodman, C.B. et al. Hydrogen Peroxide Induces Lysosomal Protease Alterations in PC12 Cells. Neurochem Res 32, 1499–1510 (2007). https://doi.org/10.1007/s11064-007-9338-5

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  • DOI: https://doi.org/10.1007/s11064-007-9338-5

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