Nimodipine inhibits N-methyl-N-nitrosourea-induced retinalphotoreceptor apoptosis in vivo
| Autor: | Zhuo Wang, Xin Chen, Yan Li, Gui Yuan Sun, Dan Wang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Retinal degeneration
Alkylating Agents Apoptosis Biology Mitochondrion N-methyl-N-nitrosourea Photoreceptor cell Rats Sprague-Dawley chemistry.chemical_compound Electroretinography medicine Animals Pharmacology (medical) RNA Messenger bcl-2-Associated X Protein Membrane Potential Mitochondrial Pharmacology Retina medicine.diagnostic_test Caspase 3 Phosphoric Diester Hydrolases Reverse Transcriptase Polymerase Chain Reaction Retinal Degeneration Methylnitrosourea Retinal Calcium Channel Blockers Flow Cytometry medicine.disease Molecular biology Rats Microscopy Electron medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 chemistry Biochemistry Female Nimodipine sense organs Erg Injections Intraperitoneal Photoreceptor Cells Vertebrate Research Article |
| Zdroj: | Indian Journal of Pharmacology |
| ISSN: | 0253-7613 |
| DOI: | 10.4103/0253-7613.108297 |
| Popis: | Purpose: The purpose of the present study was to investigate the effect of nimodipine (NMD), a calcium channel blocker, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration. Materials and Methods: 60 mg/kg MNU was given intraperitoneally to 6-week-old female Sprague-Dawley rats, and NMD was injected intraperitoneally for up to 5 days after MNU. The effect of NMD was evaluated by electron microscopy and electroretinography (ERG). Proteins of Bax, Bcl-2, Caspase-3, and mitochondrial membrane potential (MMP) were analyzed with flow cytometry. The expressions of phosphodiesterase (PDE) and Caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). Results: The apparent preservation of NMD to the photoreceptor cell was demonstrated by electron microscopy. After NMD treatment, both a- and b-waves of ERG were significantly higher compared with the control group, and had a protective effect on MNU-damaged retinal ERG. Flow cytometric assays showed that NMD decreased the level of Bax and Caspase-3 and increased the activity of Bcl-2 in retina. NMD significantly restored the mitochondrial membrane potential (MMP). RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of Caspase-3, and mRNA level of PDE was clearly upregulated. Conclusions: These data suggest that NMD may regulate the expressions of Bax, Bcl-2, Caspases-3, and PDE, and protection on the functions of retinal cell mitochondria inhibit MNU-induced photoreceptor cell apoptosis and protect retinal function in rats. |
| Databáze: | OpenAIRE |
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