Protection of retinal cells from ischemia by a novel gap junction inhibitor

Satyabrata Das; Dingbo Lin; Snehalata Jena; Aibin Shi; Srinivas Battina; Duy H. Hua; Rachel Allbaugh; Dolores J. Takemoto

doi:10.1016/j.bbrc.2008.06.069

Protection of retinal cells from ischemia by a novel gap junction inhibitor

Satyabrata Das, Dingbo Lin, Snehalata Jena, Aibin Shi, Srinivas Battina, Duy H. Hua, Rachel Allbaugh, Dolores J. Takemoto

Medicine - Cardiology Division

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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 μM. 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.

Original language	English (US)
Pages (from-to)	504-508
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	373
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.06.069
State	Published - Sep 5 2008

Bibliographical note

Funding Information:
We gratefully acknowledge the kind gift of R28 cells from Dr. Gail Seigel. This work was supported by EYRO113421 to D.J.T., NIH R01AG025500, NSF CHE-0555341 and American Heart Association 0750115Z to D.H.H.

Keywords

Caspase-3
Cobalt Chloride (CoCl)
Gap junctions
HIF1α
Hypoxia
Ischemia
PQ1
Retinal degeneration

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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 μM. 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.",

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author = "Satyabrata Das and Dingbo Lin and Snehalata Jena and Aibin Shi and Srinivas Battina and Hua, {Duy H.} and Rachel Allbaugh and Takemoto, {Dolores J.}",

note = "Funding Information: We gratefully acknowledge the kind gift of R28 cells from Dr. Gail Seigel. This work was supported by EYRO113421 to D.J.T., NIH R01AG025500, NSF CHE-0555341 and American Heart Association 0750115Z to D.H.H.",

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AU - Das, Satyabrata

AU - Lin, Dingbo

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AU - Shi, Aibin

AU - Battina, Srinivas

AU - Hua, Duy H.

AU - Allbaugh, Rachel

AU - Takemoto, Dolores J.

N1 - Funding Information: We gratefully acknowledge the kind gift of R28 cells from Dr. Gail Seigel. This work was supported by EYRO113421 to D.J.T., NIH R01AG025500, NSF CHE-0555341 and American Heart Association 0750115Z to D.H.H.

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N2 - 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 μM. 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.

AB - 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 μM. 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.

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Protection of retinal cells from ischemia by a novel gap junction inhibitor

Abstract

Bibliographical note

Keywords

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