| Role of the autophagic-lysosomal system on low potassium-induced apoptosis in cultured cerebellar granule cells. | |
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MedLine Citation:
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PMID: 15715672 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptotic and autophagic cell death have been implicated, on the basis of morphological and biochemical criteria, in neuronal loss occurring in neurodegenerative diseases and it has been shown that they may overlap. We have studied the relationship between apoptosis and autophagic cell death in cerebellar granule cells (CGCs) undergoing apoptosis following serum and potassium deprivation. We found that apoptosis is accompanied by an early and marked proliferation of autophagosomal-lysosomal compartments as detected by electron microscopy and immunofluorescence analysis. Autophagy is blocked by hrIGF-1 and forskolin, two well-known inhibitors of CGC apoptosis, as well as by adenovirus-mediated overexpression of Bcl-2. 3-Methyladenine (3-MA) an inhibitor of autophagy, not only arrests this event but it also blocks apoptosis. The neuroprotective effect of 3-MA is accompanied by block of cytochrome c (cyt c) release in the cytosol and by inhibition of caspase-3 activation which, in turn, appears to be mediated by cathepsin B, as CA074-Me, a selective inhibitor of this enzyme, fully blocks the processing of pro-caspase-3. Immunofluorescence analysis demonstrated that cathepsin B, normally confined inside the lysosomal-endosomal compartment, is released during apoptosis into the cytosol where this enzyme may act as an execution protease. Collectively, these observations indicate that autophagy precedes and is causally connected with the subsequent onset of programmed death. |
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Authors:
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Nadia Canu; Roberta Tufi; Anna Lucia Serafino; Giuseppina Amadoro; Maria Teresa Ciotti; Pietro Calissano |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurochemistry Volume: 92 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-02-17 Completed Date: 2005-04-28 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 1228-42 Citation Subset: IM |
Affiliation:
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Dipartimento di Neuroscienze, Facoltà di Medicina e Chirurgia, Università di Tor Vergata, Roma, Italia. n.canu@inmm.cnr.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
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analogs & derivatives*,
pharmacology Amino Acid Chloromethyl Ketones / pharmacology Animals Animals, Newborn Antigens, CD / metabolism Apoptosis / drug effects* Autophagy / physiology* Caspases / metabolism Cathepsins / metabolism Cell Size / drug effects Cell Survival / drug effects Cells, Cultured Cerebellum / cytology* Coumarins / pharmacology Cysteine Proteinase Inhibitors / pharmacology DNA-Binding Proteins / pharmacology Dose-Response Relationship, Drug Drug Interactions Erythroid-Specific DNA-Binding Factors Extracellular Signal-Regulated MAP Kinases / metabolism Fluorescent Antibody Technique / methods Forskolin / pharmacology Gene Expression Regulation Glycoside Hydrolases / metabolism Green Fluorescent Proteins / metabolism Lysosome-Associated Membrane Glycoproteins Lysosomes / physiology*, ultrastructure Microscopy, Electron / methods Microtubule Proteins / metabolism Neurons / drug effects*, ultrastructure Oligopeptides / pharmacology Potassium / pharmacology* Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Messenger / biosynthesis Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction / methods Teprotide / pharmacology Time Factors Transcription Factors / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Ac-aspartyl-glutamyl-valyl-aspartyl-aminomethylcoumarin; 0/Amino Acid Chloromethyl Ketones; 0/Antigens, CD; 0/Coumarins; 0/Cysteine Proteinase Inhibitors; 0/DNA-Binding Proteins; 0/Erythroid-Specific DNA-Binding Factors; 0/Lysosome-Associated Membrane Glycoproteins; 0/Microtubule Proteins; 0/Oligopeptides; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/Transcription Factors; 0/acetyl-tyrosyl-valyl-alanyl-aspartyl-7-amino-4-methylcoumarinamide; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 147336-22-9/Green Fluorescent Proteins; 35115-60-7/Teprotide; 5142-23-4/3-methyladenine; 66428-89-5/Forskolin; 73-24-5/Adenine; 7440-09-7/Potassium; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.2.1.-/Glycoside Hydrolases; EC 3.2.1.-/beta-galactanase; EC 3.4.-/Cathepsins; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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