Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
ABT-702, an adenosine kinase inhibitor, attenuates inflammation in diabetic retinopathy
Life Sciences, Volume 93, No. 2-3, Year 2013
Notification
URL copied to clipboard!
Description
Aims This study was undertaken to determine the effect of an adenosine kinase inhibitor (AKI) in diabetic retinopathy (DR). We have shown previously that adenosine signaling via A2A receptors (A2AAR) is involved in retinal protection from diabetes-induced inflammation. Here we demonstrate that AKI-enhanced adenosine signaling provides protection from DR in mice. Main methods We targeted AK, the key enzyme in adenosine metabolism, using a treatment regime with the selective AKI, ABT-702 (1.5 mg/kg intraperitoneally twice a week) commencing at the beginning of streptozotocin-induced diabetes at the age of eight weeks. This treatment, previously demonstrated to increase free adenosine levels in vivo, was maintained until the age of 16 weeks. Retinal inflammation was evaluated using Western blot, Real-Time PCR and immuno-staining analyses. Role of A 2AAR signaling in the anti-inflammation effect of ABT-702 was analyzed in Amadori-glycated-albumin (AGA)-treated microglial cells. Key findings At 16 weeks, when diabetic mice exhibit significant signs of retinal inflammation including up-regulation of oxidative/nitrosative stress, A 2AAR, ENT1, Iba1, TNF-α, ICAM1, retinal cell death, and down-regulation of AK, the ABT-702 treated group showed lower signs of inflammation compared to control animals receiving the vehicle. The involvement of adenosine signaling in the anti-inflammation effect of ABT-702 was supported by the TNF-α release blocking effect of A2AAR antagonist in AGA-treated microglial cells. Significance These results suggest a role for AK in regulating adenosine receptor signaling in the retina. Inhibition of AK potentially amplifies the therapeutic effects of site- and event-specific accumulation of extracellular adenosine, which is of highly translational impact. © 2013 Elsevier Inc.
Authors & Co-Authors
Elsherbiny, Nehal Mohsen
United States, Augusta
Augusta University
Egypt, Mansoura
Mansoura University
Ahmad, Saif
United States, Augusta
Augusta University
Naime, Mohammad
United States, Augusta
Augusta University
Elsherbini, Ahmed M.
United States, Augusta
Augusta University
Fulzele, Sadanand
United States, Augusta
Augusta University
Al-Gayyar, Mohammed M.H.
Egypt, Mansoura
Mansoura University
Eissa, Laila A.
Egypt, Mansoura
Mansoura University
El-Shishtawy, Mamdouh Mohammad
Egypt, Mansoura
Mansoura University
Liou, Gregory Ing
United States, Augusta
Augusta University
Statistics
Citations: 38
Authors: 9
Affiliations: 2
Identifiers
Doi:
10.1016/j.lfs.2013.05.024
ISSN:
00243205
e-ISSN:
18790631
Research Areas
Health System And Policy
Noncommunicable Diseases