Protection of retinal cells from ischemia by a novel gap junction inhibitor.
Biochem Biophys Res Commun
; 373(4): 504-8, 2008 Sep 05.
Article
in En
| MEDLINE
| ID: mdl-18590704
ABSTRACT
Retinal cells which become ischemic will pass apoptotic signal to adjacent cells, resulting in the spread of damage. This occurs through open gap junctions. A class of novel drugs, based on primaquine (PQ), was tested for binding to connexin 43 using simulated docking studies. A novel drug has been synthesized and tested for inhibition of gap junction activity using R28 neuro-retinal cells in culture. Four drugs were initially compared to mefloquine, a known gap junction inhibitor. The drug with optimal inhibitory activity, PQ1, was tested for inhibition and was found to inhibit dye transfer by 70% at 10 microM. Retinal ischemia was produced in R28 cells using cobalt chloride as a chemical agent. This resulted in activation of caspase-3 which was prevented by PQ1, the gap junction inhibitor. Results demonstrate that novel gap junction inhibitors may provide a means to prevent retinal damage during ischemia.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Primaquine
/
Retina
/
Retinal Vessels
/
Gap Junctions
/
Ischemia
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2008
Document type:
Article
Affiliation country:
Estados Unidos