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Hydrogen peroxide triggers the proteolytic cleavage and the inactivation of calcineurin

Cited 20 time in Web of Science Cited 20 time in Scopus
Authors
Lee, Ji-Eun; Kim, Hyungsoo; Jang, Hyonchol; Cho, Eun-Jung; Youn, Hong-Duk
Issue Date
2007-01-16
Publisher
Wiley-Blackwell
Citation
J Neurochem. 2007 Mar;100(6):1703-12. Epub 2007 Jan 8.
Keywords
Amyloid beta-Protein/pharmacologyAnimalsCalcineurin/*metabolismCells, CulturedCerebral Cortex/cytologyEmbryo, MammalianEnzyme Activation/drug effectsEnzyme Inhibitors/pharmacologyHydrogen Peroxide/*pharmacologyMiceMice, Inbred ICRMutagenesis/physiologyNeurons/*drug effectsOxidants/*pharmacologyPeptide Fragments/pharmacologyTime FactorsTransfection
Abstract
Increases in the levels of reactive oxygen species (ROS) are correlated with a decrease in calcineurin (CN) activity under oxidative or neuropathological conditions. However, the molecular mechanism underlying this ROS-mediated CN inactivation remains unclear. Here, we describe a mechanism for the inactivation of CN by hydrogen peroxide. The treatment of mouse primary cortical neuron cells with Abeta(1-42) peptide and hydrogen peroxide triggered the proteolytic cleavage of CN and decreased its enzymatic activity. In addition, hydrogen peroxide was found to cleave CN in different types of cells. Calcium influx was not involved in CN inactivation during hydrogen peroxide-mediated cleavage, but CN cleavage was partially blocked by chloroquine, indicating that an unidentified lysosomal protease is probably involved in its hydrogen peroxide-mediated cleavage. Treatment with hydrogen peroxide triggered CN cleavage at a specific sequence within its catalytic domain, and the cleaved form of CN had no enzymatic ability to dephosphorylate nuclear factor in activated T cells. Thus, our findings suggest a molecular mechanism by which hydrogen peroxide inactivates CN by proteolysis in ROS-related diseases.
ISSN
0022-3042 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17217415

http://hdl.handle.net/10371/24860
DOI
https://doi.org/10.1111/j.1471-4159.2006.04340.x
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
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