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Invest Ophthalmol Vis Sci. 2011 Jul 15;52(8):5174-82. doi: 10.1167/iovs.11-7272.

Rapid changes in connexin-43 in response to genotoxic stress stabilize cell-cell communication in corneal endothelium.

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1
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Abstract

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.

PMID:
21666237
PMCID:
PMC3176070
DOI:
10.1167/iovs.11-7272
[Indexed for MEDLINE]
Free PMC Article
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