| ortho-substituted PCB95 alters intracellular calcium signaling and causes cellular acidification in PC12 cells by an immunophilin-dependent mechanism. | |
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MedLine Citation:
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PMID: 11208908 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ortho-Substituted PCBs mobilize Ca2+ from isolated brain microsomes by interaction with FKBP12/RyR complexes. Investigation into the cellular importance of this mechanism was undertaken using PC12 cells by fluoroimaging the actions of specific PCB congeners on [Ca2+]i and pH. RyR and IP3R share a common intracellular Ca2+ store in PC12 cells. Perfusion of nM to low microM PCB95 caused a transient rise of [Ca2+]i that was not completely dependent on extracellular Ca2+. Pre-incubation of the cells with ryanodine or FK506 completely eliminated PCB95 responses, suggesting a primary action on the FKPP12/RyR-sensitive store. PCB95, but not PCB126, induced a gradual decrease in cytosolic pH that could be completely eliminated by FK506 pre-incubation of the cells. Direct respiration measurement using isolated brain mitochondria demonstrated that neither of the PCBs directly altered any stage of mitochondrial respiration. These results revealed that PCB95 disrupts intracellular Ca2+ signaling in PC12 cells by interaction with the FKBP12/RyR complex that in turn accelerated cellular metabolism, possibly affecting signaling between ER and mitochondria. Since ortho-substituted PCBs have been shown to be neurotoxic and may affect neurodevelopment, studies on the molecular mechanism by which they alter cellular signaling may provide valuable information on the physiological roles of FKPB12 and RyR on neuronal functions. |
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Authors:
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P W Wong; E F Garcia; I N Pessah |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of neurochemistry Volume: 76 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2001 Jan |
Date Detail:
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Created Date: 2002-07-23 Completed Date: 2002-08-15 Revised Date: 2007-11-14 |
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: 450-63 Citation Subset: IM |
Affiliation:
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Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acidosis
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chemically induced* Animals Bradykinin / pharmacology Brain Chemistry Calcium / metabolism Calcium Signaling / drug effects* Cell Respiration / drug effects Enzyme Inhibitors / pharmacology Estrogen Antagonists / pharmacology Hydrogen-Ion Concentration / drug effects Immunophilins / metabolism* Inositol Phosphates / metabolism Intracellular Fluid / drug effects, metabolism Male Mitochondria / chemistry, drug effects PC12 Cells Pheochromocytoma / drug therapy, metabolism* Polychlorinated Biphenyls / pharmacology* Rats Rats, Sprague-Dawley Ryanodine / pharmacology Structure-Activity Relationship Tacrolimus / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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ES046997/ES/NIEHS NIH HHS; ES05707/ES/NIEHS NIH HHS; ES10173/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Estrogen Antagonists; 0/Inositol Phosphates; 0/Polychlorinated Biphenyls; 109581-93-3/Tacrolimus; 15662-33-6/Ryanodine; 38379-99-6/2,2',3,5',6-pentachlorobiphenyl; 57465-28-8/3,4,5,3',4'-pentachlorobiphenyl; 58-82-2/Bradykinin; 7440-70-2/Calcium; EC 5.2.1.8/Immunophilins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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