| Enhanced cystatin C and lysosomal protease expression following 6-hydroxydopamine exposure. | |
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MedLine Citation:
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PMID: 16414118 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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6-Hydroxydopamine (6-OHDA) is a selective neurotoxin used to induce apoptosis in catecholamine-containing neurons. Although biochemical products and reactive oxygen species (ROS) of 6-OHDA have been well documented, the activation of cellular pathways following exposure are not well understood. Apoptosis in PC12 (Pheochromocytoma) cells was induced by 6-OHDA in a dose (10-150 microM) and time-dependent (24-72 h) manner compared to experimental controls (no treatment). PC 12 cells exposed to 50 microM 6-OHDA demonstrated the involvement of caspase 3 and lysosomal protease alterations. Following 6-OHDA exposure, the caspase 3-like inhibitor Ac-DEVD-CHO significantly decreased 6-OHDA induced cell death. In addition, alterations in expression of the lysosomal cysteine and aspartic proteases, cathepsin B (CB) and cathepsin D (CD) and the endogenous cysteine protease inhibitor cystatin C were observed utilizing immunocytochemical analysis at 24, 48, and 72 h following 6-OHDA exposure. Furthermore, CB and CD and cystatin C immuno-like reactivity was more pronounced in TUNEL positive cells. Moreover, Western blot analysis confirmed a significant increase in protein expression for CB and CD at 72 h and a temporal and concentration dependent increase in cystatin C in response to 6-OHDA. Cells treated with pepstatin A, an inhibitor for CD, showed a significant decrease in cell death, however, CA-074ME, a specific inhibitor for CB, failed to protect cells from 6-OHDA induced cell death. Thus, these results suggest that apoptosis induced by 6-OHDA exposure is mediated in part through caspase 3 activation and lysosomal protease CD. |
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Authors:
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Daniel C Lee; Fran T Close; Carl B Goodman; Inneke M Jackson; Ceceile Wight-Mason; Lateesha M Wells; Tracy A Womble; Donald E Palm |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-01-18 |
Journal Detail:
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Title: Neurotoxicology Volume: 27 ISSN: 0161-813X ISO Abbreviation: Neurotoxicology Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-02-13 Completed Date: 2006-05-22 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7905589 Medline TA: Neurotoxicology Country: Netherlands |
Other Details:
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Languages: eng Pagination: 260-76 Citation Subset: IM |
Affiliation:
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College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Blotting, Western Caspase 3 Caspases / metabolism Cathepsin B / biosynthesis Cathepsin D / biosynthesis Cell Death / drug effects Cell Proliferation / drug effects Cell Survival / drug effects Cystatin C Cystatins / biosynthesis* Cytochromes c / metabolism DNA / biosynthesis, genetics Humans Immunohistochemistry In Situ Nick-End Labeling L-Lactate Dehydrogenase / metabolism Lysosomes / drug effects, enzymology* Oxidative Stress / drug effects Oxidopamine / toxicity* PC12 Cells Peptide Hydrolases / biosynthesis* Poly(ADP-ribose) Polymerases / metabolism Rats Stimulation, Chemical Sympatholytics / toxicity* |
| Grant Support | |
ID/Acronym/Agency:
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G12RR03020/RR/NCRR NIH HHS; S06 GM 0811/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CST3 protein, human; 0/Cst3 protein, rat; 0/Cystatin C; 0/Cystatins; 0/Sympatholytics; 1199-18-4/Oxidopamine; 9007-43-6/Cytochromes c; 9007-49-2/DNA; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.-/Peptide Hydrolases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.1/Cathepsin B; EC 3.4.23.5/Cathepsin D |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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