Neurovascular protective effect of FeTPPs in N-methyl-D-aspartate model: similarities to diabetes.
Abstract
We have previously shown a causal role of peroxynitrite in mediating retinal ganglion cell (RGC) death in diabetic and neurotoxicity models. In the present study, the role of peroxynitrite in altering the antioxidant and antiapoptotic thioredoxin (Trx) system will be investigated as well as the subsequent effects on glial activation and capillary degeneration. Excitotoxicity of the retina was induced by intravitreal injection of N-methyl-d-aspartate (NMDA) in rats, which also received the peroxynitrite decomposition catalyst FeTPPs. RGC loss was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and GC count. Glial activation and nitrotyrosine were assessed by immunohistochemistry. Acellular capillaries and pericytes were counted in retinal trypsin digest. NMDA-induced peroxynitrite formation caused RGC loss, which was associated with enhanced expression of Trx and its endogenous inhibitor thioredoxin interacting protein. The results also showed enhanced thioredoxin interacting protein/Trx binding and disruption of the Trx/apoptosis signal-regulating kinase 1 "inhibitory complex," leading to release of apoptosis signal-regulating kinase 1 and activation of the apoptotic pathway, as evidenced by p3...Continue Reading
References
A possible interaction of thioredoxin with VDUP1 in HeLa cells detected in a yeast two-hybrid system
Citations
Diabetes and overexpression of proNGF cause retinal neurodegeneration via activation of RhoA pathway
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