| Paclitaxel induces calcium oscillations via an inositol 1,4,5-trisphosphate receptor and neuronal calcium sensor 1-dependent mechanism. | |
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MedLine Citation:
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PMID: 17114292 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Taxol (Paclitaxel) is an important natural product for the treatment of solid tumors. Despite a well documented tubulin-stabilizing effect, many side effects of taxol therapy cannot be explained by cytoskeletal mechanisms. In the present study submicromolar concentrations of taxol, mimicking concentrations found in patients, induced cytosolic calcium (Ca(2+)) oscillations in a human neuronal cell line. These oscillations were independent of extracellular and mitochondrial Ca(2+) but dependent on intact signaling via the phosphoinositide signaling pathway. We identified a taxol binding protein, neuronal Ca(2+) sensor 1 (NCS-1), a Ca(2+) binding protein that interacts with the inositol 1,4,5-trisphosphate receptor from a human brain cDNA phage display library. Taxol increased binding of NCS-1 to the inositol 1,4,5-trisphosphate receptor. Short hairpin RNA-mediated knockdown of NCS-1 in the same cell line abrogated the response to taxol but not to other agonists stimulating the phosphoinositide signaling pathway. These findings are important for studies involving taxol as a research tool in cell biology and may help to devise new strategies for the management of side effects induced by taxol therapy. |
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Authors:
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Wolfgang Boehmerle; Ute Splittgerber; Michael B Lazarus; Kathleen M McKenzie; David G Johnston; David J Austin; Barbara E Ehrlich |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-11-17 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 103 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-11-29 Completed Date: 2007-01-19 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 18356-61 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Yale University, New Haven, CT 06520, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biotin
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chemistry Calcium / metabolism Calcium Signaling / drug effects* Cell Line, Tumor Endoplasmic Reticulum / drug effects, metabolism Humans Inositol 1,4,5-Trisphosphate Receptors / metabolism* Neuroblastoma / metabolism Neuronal Calcium-Sensor Proteins / genetics, metabolism* Neuropeptides / genetics, metabolism* Paclitaxel / chemistry, pharmacology* RNA Interference |
| Grant Support | |
ID/Acronym/Agency:
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GM59673/GM/NIGMS NIH HHS; GM63496/GM/NIGMS NIH HHS; R43 AT00324-01/AT/NCCAM NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Inositol 1,4,5-Trisphosphate Receptors; 0/Neuronal Calcium-Sensor Proteins; 0/Neuropeptides; 0/frequenin calcium sensor proteins; 33069-62-4/Paclitaxel; 58-85-5/Biotin; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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