Physiological significance of recombination‐activating gene 1 in neuronal death, especially optic neuropathy
2015
Hirano, Takao | Murata, Toshinori | Hayashi, Takuma
Although the transcription factor nuclear factor‐κB (NF‐κB) is known to regulate cell death and survival, its precise role in cell death within the central nervous system remains unknown. We previously reported that mice with a homozygous deficiency for NF‐κBp50 spontaneously develop optic neuropathy. The aim of the present study was to demonstrate the expression and activation of the proapoptotic factor(s) that mediate optic neuropathy in p50‐deficient mice. Recombination‐activating gene (Rag) 1 is known to activate the recombination of immunoglobulin V(D)J. In this study, experiments with genetically engineered mice revealed the involvement of Rag1 expression in apoptosis of Brn3a‐positive retinal ganglion cells, and also demonstrated the specific effect of p50 deficiency on the activation of Rag1 gene transcription. Furthermore, genetic analysis of murine neuronal stem‐like cells clarified the biological significance of Rag1 in N‐methyl‐d‐aspartate‐induced neuronal apoptosis. We also detected the apoptosis‐regulating factors Bax and cleaved caspase 3, 8 and 9 in HEK293 cells transfected‐molecule of Rag1, and a human histological examination revealed the expression of Rag1 in retinal ganglion cells. The results of the present study indicate that Rag1 plays a role in optic neuropathy as a proapoptotic candidate in p50‐deficient mice. This finding may lead to new therapeutic targets in optic neuropathy.
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