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Neuroprotective Effects of Inhibiting Fyn S-Nitrosylation on Cerebral Ischemia/Reperfusion-Induced Damage to CA1 Hippocampal Neurons.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2016 Jul 12; Vol. 17 (7). Date of Electronic Publication: 2016 Jul 12. - Publication Year :
- 2016
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Abstract
- Nitric oxide (NO) can regulate signaling pathways via S-nitrosylation. Fyn can be post-translationally modified in many biological processes. In the present study, using a rat four-vessel-occlusion ischemic model, we aimed to assess whether Fyn could be S-nitrosylated and to evaluate the effects of Fyn S-nitrosylation on brain damage. In vitro, Fyn could be S-nitrosylated by S-nitrosoglutathione (GSNO, an exogenous NO donor), and in vivo, endogenous NO synthesized by NO synthases (NOS) could enhance Fyn S-nitrosylation. Application of GSNO, 7-nitroindazole (7-NI, an inhibitor of neuronal NOS) and hydrogen maleate (MK-801, the N-methyl-d-aspartate receptor (NMDAR) antagonist) could decrease the S-nitrosylation and phosphorylation of Fyn induced by cerebral ischemia/reperfusion (I/R). Cresyl violet staining validated that these compounds exerted neuroprotective effects against the cerebral I/R-induced damage to hippocampal CA1 neurons. Taken together, in this study, we demonstrated that Fyn can be S-nitrosylated both in vitro and in vivo and that inhibiting S-nitrosylation can exert neuroprotective effects against cerebral I/R injury, potentially via NMDAR-mediated mechanisms. These findings may lead to a new field of inquiry to investigate the underlying pathogenesis of stroke and the development of novel treatment strategies.
- Subjects :
- Animals
Disease Models, Animal
Dizocilpine Maleate pharmacology
Dizocilpine Maleate therapeutic use
HEK293 Cells
Hippocampus metabolism
Humans
Male
Nitric Oxide metabolism
Nitric Oxide Donors pharmacology
Nitric Oxide Donors therapeutic use
Nitric Oxide Synthase Type I metabolism
Phosphorylation drug effects
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate metabolism
Reperfusion Injury drug therapy
Reperfusion Injury metabolism
S-Nitrosoglutathione pharmacology
Signal Transduction drug effects
Hippocampus drug effects
Neuroprotective Agents pharmacology
Protein Processing, Post-Translational drug effects
Proto-Oncogene Proteins c-fyn metabolism
Reperfusion Injury pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 17
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 27420046
- Full Text :
- https://doi.org/10.3390/ijms17071100