| First Author | Hirano T | Year | 2015 |
| Journal | FEBS J | Volume | 282 |
| Issue | 1 | Pages | 129-41 |
| PubMed ID | 25312244 | Mgi Jnum | J:237030 |
| Mgi Id | MGI:5810533 | Doi | 10.1111/febs.13109 |
| Citation | Hirano T, et al. (2015) Physiological significance of recombination-activating gene 1 in neuronal death, especially optic neuropathy. FEBS J 282(1):129-41 |
| abstractText | Although the transcription factor nuclear factor-kappaB (NF-kappaB) 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-kappaBp50 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. |
