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
pharmacology, toxicology and pharmaceutics
Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity
British Journal of Pharmacology, Volume 164, No. 1, Year 2011
Notification
URL copied to clipboard!
Description
BACKGROUND AND PURPOSE Up-regulation of thioredoxin interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (Trx), compromises cellular antioxidant and anti-apoptotic defences and stimulates pro-inflammatory cytokines expression, implying a role for TXNIP in apoptosis. Here we have examined the causal role of TXNIP expression in mediating retinal neurotoxicity and assessed the neuroprotective actions of verapamil, a calcium channel blocker and an inhibitor of TXNIP expression. EXPERIMENTAL APPROACH Retinal neurotoxicity was induced by intravitreal injection of NMDA in Sprague-Dawley rats, which received verapamil (10 mg·kg -1, p.o.) or vehicle. Neurotoxicity was examined by terminal dUTP nick-end labelling assay and ganglion cell count. Expression of TXNIP, apoptosis signal-regulating kinase 1 (ASK-1), NF-κB, p38 MAPK, JNK, cleaved poly-ADP-ribose polymerase (PARP), caspase-3, nitrotyrosine and 4-hydroxy-nonenal were examined by Western and slot-blot analysis. Release of TNF-α and IL-1β was examined by elisa. KEY RESULTS NMDA injection enhanced TXNIP expression, decreased Trx activity, causing increased oxidative stress, glial activation and release of TNF-α and IL-1β. Enhanced TXNIP expression disrupted Trx/ASK-1 inhibitory complex leading to release of ASK-1 and activation of the pro-apoptotic p38 MAPK/JNK pathway, as indicated by cleaved PARP and caspase-3 expression. Treatment with verapamil blocked these effects. CONCLUSION AND IMPLICATIONS Elevated TXNIP expression contributed to retinal neurotoxicity by three different mechanisms, inducing release of inflammatory mediators such as TNF-α and IL-1β, altering antioxidant status and disrupting the Trx-ASK-1 inhibitory complex leading to activation of the p38 MAPK/JNK apoptotic pathway. Targeting TXNIP expression is a potential therapeutic target for retinal neurodegenerative disease. © 2011 The British Pharmacological Society.
Authors & Co-Authors
Al-Gayyar, Mohammed M.H.
United States, Athens
University of Georgia
United States, Augusta
Medical College of Georgia
United States
Va Medical Center
Egypt, Mansoura
Mansoura University
Abdelsaid, Mohammed A.
United States, Athens
University of Georgia
United States, Augusta
Medical College of Georgia
United States
Va Medical Center
Matragoon, Suraporn
United States, Athens
University of Georgia
United States, Augusta
Medical College of Georgia
United States
Va Medical Center
Pillai, Bindu A.
United States, Athens
University of Georgia
United States, Augusta
Medical College of Georgia
United States
Va Medical Center
El-Remessy, Azza B.
United States, Athens
University of Georgia
United States, Augusta
Medical College of Georgia
United States
Va Medical Center
Statistics
Citations: 92
Authors: 5
Affiliations: 4
Identifiers
Doi:
10.1111/j.1476-5381.2011.01336.x
ISSN:
00071188
e-ISSN:
14765381
Research Areas
Cancer
Health System And Policy