| Proteasome inhibitor lactacystin induces cholinergic degeneration. | |
| | |
MedLine Citation:
|
PMID: 20437934 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture. METHODS: We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the AnnexinV-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA. RESULTS: We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly. CONCLUSIONS: Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation. |
| | |
Authors:
|
Hai-Yan Zhou; Yu-Yan Tan; Zhi-Quan Wang; Gang Wang; Guo-Qiang Lu; Sheng-Di Chen |
Related Documents
:
|
1472104 - Effects of diarylsulfonylurea antitumor agents on the function of mitochondria isolated... 7543484 - New knowledge in primary biliary cirrhosis. 18483464 - Head and neck cancer cell lines are resistant to mitochondrial-depolarization-induced a... 20382214 - Quantitation of (a)symmetric inheritance of functional and of oxidatively damaged mitoc... 2499774 - Cytogenetical characterisation of chinese hamster 43-3b transferants with the amplified... 23197904 - Interleukin-17 and interleukin-22 induced proinflammatory cytokine production in kerati... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques Volume: 37 ISSN: 0317-1671 ISO Abbreviation: Can J Neurol Sci Publication Date: 2010 Mar |
Date Detail:
|
Created Date: 2010-05-04 Completed Date: 2010-05-27 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0415227 Medline TA: Can J Neurol Sci Country: Canada |
Other Details:
|
Languages: eng Pagination: 229-34 Citation Subset: IM |
Affiliation:
|
Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcholine
/
metabolism* Acetylcysteine / analogs & derivatives*, pharmacology Animals Annexin A5 / metabolism Apoptosis / drug effects* Cell Line, Transformed Cell Survival / drug effects Cysteine Proteinase Inhibitors / pharmacology* Dose-Response Relationship, Drug Flow Cytometry / methods Gene Expression Regulation / drug effects Membrane Potential, Mitochondrial / drug effects Mice Oxidative Stress / drug effects Reactive Oxygen Species / metabolism Ubiquitin C / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Annexin A5; 0/Cysteine Proteinase Inhibitors; 0/Reactive Oxygen Species; 0/Ubiquitin C; 133343-34-7/lactacystin; 51-84-3/Acetylcholine; 616-91-1/Acetylcysteine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Quercetin administration after spinal cord trauma changes S-100 levels.
Next Document: Utility of transcranial doppler in idiopathic intracranial hypertension.