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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2009-10-30
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pubmed:abstractText |
The finding of nuclear translocation of cathepsin L and its ability to process the CDP/Cux transcription factor uncovers an important role of cathepsin L in control of cell cycle progression. As the expression of certain cell cycle regulators is associated with nigral neuronal death, the present study was sought to investigate if nuclear translocation of cathepsin L and expression of certain cyclins were induced in DA neurons by 6-hydroxydopamine (6-OHDA). The neuroprotective effects of the cell cycle inhibitor olomoucine against 6-OHDA-induced death of nigral neurons were examined. Using immunocytochemistry and real-time PCR we demonstrated that cyclin D1, cyclin B1 and proliferating cell nuclear antigen (PCNA) were aberrantly expressed in some dopaminergic neurons after 6-OHDA infusion. The nuclear translocation of cathepsin L and up-regulation of LC3, a protein involved in autophagy, were observed in nigral DA neurons. Olomoucine, a cyclin dependent kinase (CDK) inhibitor, reduced contralateral rotations and the loss of TH-positive neurons in substantia nigra induced by lesion with 6-OHDA. Pretreatment of rats or primary DA neurons with olomoucine resulted in a partial blockade of nuclear translocation of cathepsin L. Olomoucine also increased the expression of punctate LC3 immunoreactivity, indicating activation of autophagy. These findings suggest that olomoucine may exert neuroprotective effects through inhibiting cathepsin L nuclear translocation and activating autophagy.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin L,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Ctsl protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Kinetin,
http://linkedlifedata.com/resource/pubmed/chemical/LC3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/olomoucine
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1872-6240
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
1264
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
85-97
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19368812-Analysis of Variance,
pubmed-meshheading:19368812-Animals,
pubmed-meshheading:19368812-Autophagy,
pubmed-meshheading:19368812-Cathepsin L,
pubmed-meshheading:19368812-Cathepsins,
pubmed-meshheading:19368812-Cell Count,
pubmed-meshheading:19368812-Cell Cycle,
pubmed-meshheading:19368812-Cell Death,
pubmed-meshheading:19368812-Cells, Cultured,
pubmed-meshheading:19368812-Cyclin B,
pubmed-meshheading:19368812-Cyclin D1,
pubmed-meshheading:19368812-Cysteine Endopeptidases,
pubmed-meshheading:19368812-Enzyme Inhibitors,
pubmed-meshheading:19368812-Fluorescent Antibody Technique,
pubmed-meshheading:19368812-Kinetin,
pubmed-meshheading:19368812-Male,
pubmed-meshheading:19368812-Microtubule-Associated Proteins,
pubmed-meshheading:19368812-Neurons,
pubmed-meshheading:19368812-Oxidopamine,
pubmed-meshheading:19368812-Parkinson Disease, Secondary,
pubmed-meshheading:19368812-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:19368812-Protein Transport,
pubmed-meshheading:19368812-Rats,
pubmed-meshheading:19368812-Rats, Sprague-Dawley,
pubmed-meshheading:19368812-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19368812-Substantia Nigra,
pubmed-meshheading:19368812-Time Factors,
pubmed-meshheading:19368812-Tyrosine 3-Monooxygenase,
pubmed-meshheading:19368812-Up-Regulation
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pubmed:year |
2009
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pubmed:articleTitle |
Olomoucine inhibits cathepsin L nuclear translocation, activates autophagy and attenuates toxicity of 6-hydroxydopamine.
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pubmed:affiliation |
Department of Pharmacology, Soochow University School of Medicine, Suzhou, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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