Document Detail


Modulation of [Ca2+]i signaling dynamics and metabolism by perinuclear mitochondria in mouse parotid acinar cells.
MedLine Citation:
PMID:  14699167     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Parotid acinar cells exhibit rapid cytosolic calcium signals ([Ca2+]i) that initiate in the apical region but rapidly become global in nature. These characteristic [Ca2+]i signals are important for effective fluid secretion, which critically depends on a synchronized activation of spatially separated ion fluxes. Apically restricted [Ca2+]i signals were never observed in parotid acinar cells. This is in marked contrast to the related pancreatic acinar cells, where the distribution of mitochondria has been suggested to contribute to restricting [Ca2+]i signals to the apical region. Therefore, the aim of this study was to determine the mitochondrial distribution and the role of mitochondrial Ca2+ uptake in shaping the spatial and temporal properties of [Ca2+]i signaling in parotid acinar cells. Confocal imaging of cells stained with MitoTracker dyes (MitoTracker Green FM or MitoTracker CMXRos) and SYTO dyes (SYTO-16 and SYTO-61) revealed that a majority of mitochondria is localized around the nucleus. Carbachol (CCh) and caged inositol 1,4,5-trisphosphate-evoked [Ca2+]i signals were delayed as they propagated through the nucleus. This delay in the CCh-evoked nuclear [Ca2+]i signal was abolished by inhibition of mitochondrial Ca2+ uptake with ruthenium red and Ru360. Likewise, simultaneous measurement of [Ca2+]i with mitochondrial [Ca2+] ([Ca2+]m), using fura-2 and rhod-FF, respectively, revealed that mitochondrial Ca2+ uptake was also inhibited by ruthenium red and Ru360. Finally, at concentrations of agonist that evoke[Ca2+]i oscillations, mitochondrial Ca2+ uptake, and a nuclear [Ca2+] delay, CCh also evoked a substantial increase in NADH autofluorescence. This autofluorescence exhibited a predominant perinuclear localization that was also sensitive to mitochondrial inhibitors. These data provide evidence that perinuclear mitochondria and mitochondrial Ca2+ uptake may differentially shape nuclear [Ca2+] signals but more importantly drive mitochondrial metabolism to generate ATP close to the nucleus. These effects may profoundly affect a variety of nuclear processes in parotid acinar cells while facilitating efficient fluid secretion.
Authors:
Jason I E Bruce; David R Giovannucci; Greg Blinder; Trevor J Shuttleworth; David I Yule
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-12-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-22     Completed Date:  2004-05-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12909-17     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. jason.bruce@urmc.rochester.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / chemistry
Animals
Calcium / chemistry,  metabolism*
Carbachol / pharmacology
Cell Nucleus / metabolism*
Cytosol / metabolism
Fluorescent Dyes / pharmacology
Image Processing, Computer-Assisted
Inositol 1,4,5-Trisphosphate / metabolism
Ions
Kinetics
Light
Mice
Microscopy, Confocal
Mitochondria / metabolism
NAD / chemistry
Oscillometry
Parotid Gland / cytology*
Ruthenium Compounds / pharmacology
Ruthenium Red / pharmacology
Signal Transduction
Time Factors
Grant Support
ID/Acronym/Agency:
DE 013539/DE/NIDCR NIH HHS; DE 14756/DE/NIDCR NIH HHS; GM 40457/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Fluorescent Dyes; 0/Ions; 0/Ru 360; 0/Ruthenium Compounds; 11103-72-3/Ruthenium Red; 51-83-2/Carbachol; 53-84-9/NAD; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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