Taurine suppresses the spread of cell death in electrically coupled RPE cells

To determine whether taurine exerts a protective effect on retinal pigment epithelium (RPE) cells exposed to a cytotoxic agent, cytochrome C (cyC), shown previously to induce apoptosis and produce cell death in electrically coupled neighboring cells. Monolayer cultures of confluent human RPE (ARPE-1...

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Bibliographic Details
Published in:Molecular vision 2008-10, Vol.14, p.1940-1950
Main Authors: Udawatte, Chandani, Qian, Haohua, Mangini, Nancy J, Kennedy, Brian G, Ripps, Harris
Format: Article
Language:English
Subjects:
Caspase 3 - metabolism
Cell Death - drug effects
Cell Line
Coloring Agents
Connexins - metabolism
Electric Conductivity
Humans
In Situ Nick-End Labeling
Intercellular Junctions - drug effects
Intercellular Junctions - metabolism
Retinal Pigment Epithelium - cytology
Retinal Pigment Epithelium - enzymology
Taurine - pharmacology
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Summary:To determine whether taurine exerts a protective effect on retinal pigment epithelium (RPE) cells exposed to a cytotoxic agent, cytochrome C (cyC), shown previously to induce apoptosis and produce cell death in electrically coupled neighboring cells. Monolayer cultures of confluent human RPE (ARPE-19) cells, which express gap-junctional proteins, were incubated in culture medium with or without taurine. After scrape loading cyC into the cells, we assayed these cells for caspase 3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine the spread of apoptosis. We found that cyC, too large a molecule to traverse gap junctional channels, produced apoptosis in cells injured by the scrape as well as those distant from the site of the scrape, presumably by the intercellular transmission of a toxic agent through the gap junctions that couple these cells. Incubation in taurine, or the gap-junction blocker, octanol, before application of cyC, reduced significantly the fraction of cells undergoing apoptosis. Voltage clamp recordings from electrically coupled Xenopus oocytes transfected with Cx43 showed that junctional communication was unaffected by taurine. Our results indicate that taurine can serve to suppress cell death in RPE cells independent of any effect on gap junctions. We have considered various avenues by which taurine can exert its protective effect, but the precise mechanism involved under these experimental conditions has yet to be identified.
ISSN:1090-0535