| Autor: |
Kenji Sakamoto, Tatsuya Okuwaki, Hiroko Ushikubo, Asami Mori, Tsutomu Nakahara, Kunio Ishii |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 135, Iss 2, Pp 72-80 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2017.09.031 |
| Popis: |
We reported that high-mobility group Box-1 (HMGB1) was involved in excitoneurotoxicity in the retina. HMGB1 is known to activate nuclear factor kappa B (NF-κB). However, the role of NF-κB in excitotoxicity is still controversial. Here, we demonstrated that NF-κB activation induced by NMDA led to the retinal neurotoxicity. Male SpragueâDawley rats were used, and NMDA (200 nmol/eye) and bovine HMGB1 (15 μg/eye) were intravitreally injected. Triptolide (500 pmol/eye), BAY 11-7082 (500 pmol/eye), and IMD-0354 (7.5 nmol/eye), NF-κB inhibitors, were co-injected with NMDA or HMGB1. Retinal sections were obtained seven days after intravitreal injection. Cell loss in the ganglion cell layer was observed in the HMGB1- and the NMDA-treated retina. All of the NF-κB inhibitors used in this study reduced the damage. BAY 11-7082 reduced the expression of phosphorylated NF-κB 12 h after NMDA injection, upregulation of GFAP immunoreactivity induced by NMDA 12 and 48 h after NMDA injection, and the number of TUNEL-positive cells 48 h after NMDA injection. The results suggest that NF-κB activation is one of the mechanisms of the retinal neuronal death that occurs 48 h after NMDA injection or later. Prevention of NF-kB activation is a candidate for the treatment of retinal neurodegeneration associated with excitotoxicity. Keywords: N-methyl-d-aspartic acid, Nuclear factor kappa B, High-mobility group Box-1, Retina |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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