Document Detail


Rapid changes in connexin-43 in response to genotoxic stress stabilize cell-cell communication in corneal endothelium.
MedLine Citation:
PMID:  21666237     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To determine how corneal endothelial (CE) cells respond to acute genotoxic stress through changes in connexin-43 (Cx43) and gap junction intercellular communication (GJIC).
METHODS: Cultured bovine CE cells were exposed to mitomycin C or other DNA-damaging agents. Changes in the levels, stability, binding partners, and trafficking of Cx43 were assessed by Western blot analysis and immunostaining. Live-cell imaging of a Cx43-green fluorescent protein (GFP) fusion protein was used to evaluate internalization of cell surface Cx43. Dye transfer and fluorescent recovery after photobleaching (FRAP) assessed GJIC.
RESULTS: After genotoxic stress, Cx43 accumulated in large gap junction plaques, had reduced zonula occludens-1 binding, and displayed increased stability. Live-cell imaging of Cx43-GFP plaques in stressed CE cells revealed reduced gap junction internalization and degradation compared to control cells. Mitomycin C enhanced transport of Cx43 from the endoplasmic reticulum to the cell surface and formation of gap junction plaques. Mitomycin C treatment also protected GJIC from disruption after cytokine treatment.
DISCUSSION: These results show a novel CE cell response to genotoxic stress mediated by marked and rapid changes in Cx43 and GJIC. This stabilization of cell-cell communication may be an important early adaptation to acute stressors encountered by CE.
Authors:
Danny S Roh; James L Funderburgh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-15
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  52     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-18     Completed Date:  2011-09-13     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5174-82     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport / drug effects
Cattle
Cell Communication / drug effects,  physiology*
Cell Membrane / metabolism
Cells, Cultured
Connexin 43 / metabolism*
DNA Damage / physiology*
Drug Stability
Endoplasmic Reticulum / metabolism
Endothelium, Corneal / cytology*,  physiology*
Gap Junctions / physiology*
Green Fluorescent Proteins / pharmacokinetics
Luminescent Agents / pharmacokinetics
Mitomycin / pharmacology
Time Factors
Tissue Distribution
Grant Support
ID/Acronym/Agency:
EY009368/EY/NEI NIH HHS; EY016415/EY/NEI NIH HHS; F30-AG035443/AG/NIA NIH HHS; P30-EY008098/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Connexin 43; 0/Luminescent Agents; 147336-22-9/Green Fluorescent Proteins; 50-07-7/Mitomycin
Comments/Corrections

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


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