Neurovascular protective effect of FeTPPs in N-methyl-D-aspartate model: similarities to diabetes.

The American Journal of Pathology
Mohammed M H Al-GayyarA B El-Remessy

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

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Citations

Sep 12, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Fuka OikawaKunio Ishii
May 23, 2012·Antioxidants & Redox Signaling·Samuel LeeRichard T Lee
Dec 5, 2012·Biological & Pharmaceutical Bulletin·Yo TsudaKunio Ishii
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Dec 3, 2013·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Asami MoriKunio Ishii
Dec 24, 2019·Reproduction in Domestic Animals = Zuchthygiene·María José ContrerasRicardo Felmer
Nov 22, 2017·Journal of Ophthalmology·Dan NingHe-Bin Tang
Sep 29, 2019·International Journal of Molecular Sciences·Daiki AsanoTsutomu Nakahara
Mar 26, 2011·British Journal of Pharmacology·Mohammed M H Al-GayyarAzza B El-Remessy
Oct 21, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Marianne BerdugoFrancine Behar-Cohen
Apr 21, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lijuan ZhuJine Yi

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