| Thapsigargin-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells. | |
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MedLine Citation:
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PMID: 16982147 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Uncontrolled calcium stress has been linked causally to a variety of neurodegenerative diseases, including ischemia, excitotoxicity and Alzheimer's disease. Thapsigargin, which increases [Ca2+]i, induces apoptotic cell death (chromatin condensation and DNA fragmentation) accompanied by caspase-3 activation in PC12 cells. We examined whether GSK-3 is involved in thapsigargin-induced cell death by using GSK-3 inhibitors in PC12 cells. Cells treated with 0.1 microM thapsigargin for 24h shrank. The injured cells underwent chromatin condensation and nuclear fragmentation, indicating apoptotic cell death. We assayed the effects of selective GSK-3 inhibitors, SB216763, azakenpaullone and alsteropaullone on thapsigargin-induced apoptosis. These inhibitors completely protected cells from thapsigargin-induced apoptosis. Alsterpaullone did not reduce the GRP78 protein expression induced by thapsigargin, suggesting that GSK-3 activation is not involved in induction of GRP78. In addition, GSK-3 inhibitors inhibited caspase-3 activation accompanied by thapsigargin-induced apoptosis. We showed in this report that thapsigargin-induced apoptosis is prevented by GSK-3 inhibitors, suggesting that thapsigargin induces caspase-dependent apoptosis mediated through GSK-3 activation in PC12 cells. |
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Authors:
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Tsuneo Takadera; Ryoko Yoshikawa; Takao Ohyashiki |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-09-18 |
Journal Detail:
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Title: Neuroscience letters Volume: 408 ISSN: 0304-3940 ISO Abbreviation: Neurosci. Lett. Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-10-10 Completed Date: 2007-04-06 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7600130 Medline TA: Neurosci Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 124-8 Citation Subset: IM |
Affiliation:
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Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1148, Japan. t-takadera@hokuriku-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects*, physiology Benzazepines / pharmacology Enzyme Inhibitors / pharmacology* Glycogen Synthase Kinase 3 / antagonists & inhibitors* Heat-Shock Proteins / metabolism Indoles / pharmacology Maleimides / pharmacology Molecular Chaperones / metabolism Neuroprotective Agents / pharmacology PC12 Cells / drug effects* Rats Thapsigargin / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Benzazepines; 0/Enzyme Inhibitors; 0/Heat-Shock Proteins; 0/Hspa5 protein, rat; 0/Indoles; 0/Maleimides; 0/Molecular Chaperones; 0/Neuroprotective Agents; 0/SB 216763; 0/alsterpaullone; 67526-95-8/Thapsigargin; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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