Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO-1 induction in retinal ganglion cells
| Autor: | Yoshiki Koriyama, Kazuhiro Ogai, Kunizo Arai, Tsuneo Takadera, Marie Kamiya, Satoru Kato, Kayo Sugitani |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Retinal Ganglion Cells Chromatin Immunoprecipitation Keap1 Vasodilator Agents Blotting Western HO-1 medicine.disease_cause Polymerase Chain Reaction Neuroprotection Retinal ganglion Cell Line Propanolamines Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Nipradilol medicine Animals Retinal ganglion cell Adaptor Proteins Signal Transducing DNA Primers Kelch-Like ECH-Associated Protein 1 Base Sequence Chemistry Nitric oxide Cell Biology S-Nitrosylation Anatomy Immunohistochemistry KEAP1 S-nitrosylation Cell biology Mice Inbred C57BL Cytoskeletal Proteins medicine.anatomical_structure Oxidative stress Enzyme Induction NIP Heme Oxygenase-1 |
| Zdroj: | Neurochemistry International. 61:1242-1253 |
| ISSN: | 0197-0186 |
| Popis: | Nipradilol (Nip), which has α1- and β-adrenoceptor antagonist and nitric oxide (NO)-donating properties, has clinically been used as an anti-glaucomatous agent in Japan. NO mediates cellular signaling pathways that regulate physiological functions. The major signaling mechanisms mediated by NO are cGMP-dependent signaling and protein S-nitrosylation-dependent signalings. Nip has been described as having neuroprotective effects through cGMP-dependent pathway in retinal ganglion cells (RGCs). However, the effect seems to be partial. On the other hand, whether Nip can prevent cell death through S-nitrosylation is not yet clarified. In this study, we therefore focused on the neuroprotective mechanism of Nip through S-nitrosylation. Nip showed a dramatic neuroprotective effect against oxidative stress-induced death of RGC-5 cells. However, denitro-nipradilol, which does not have NO-donating properties, was not protective against oxidative stress. Furthermore, an NO scavenger significantly reversed the protective action of Nip against oxidative stress. In addition, we demonstrated that α1- or β-adrenoceptor antagonists (prazosin or timolol) did not show any neuroprotective effect against oxidative stress in RGC-5 cells. We also demonstrated that Nip induced the expression of the NO-dependent antioxidant enzyme, heme oxygenase-1 (HO-1). S-nitrosylation of Kelch-like ECH-associated protein by Nip was shown to contribute to the translocation of NF-E2-related factor 2 to the nucleus, and triggered transcriptional activation of HO-1. Furthermore, RGC death and levels of 4-hydroxy-2-nonenal (4HNE) were increased after optic nerve injury in vivo. Pretreatment with Nip significantly suppressed RGC death and accumulation of 4HNE after injury through an HO-1 activity-dependent mechanism. These data demonstrate a novel neuroprotective action of Nip against oxidative stress-induced RGC death in vitro and in vivo. © 2012 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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