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T-H Wu, FY Chau, SK S Chiang, MO M Tso; Antiapoptotic and Proapoptotic Roles of NFkB in Light-Induced Photoreceptor Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3723.
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Purpose: Nuclear factor-kB (NF-kB) is a transcription factor that plays an important role in neuronal cell apoptosis. In a previous study, we demonstrated that light activates NF-kB in photoreceptor cells in vivo. In this study, we examined the antiapoptotic and proapoptotic roles of NF-kB in light-induced photoreceptor degeneration. The expression levels of NF-kB target candidate genes, namely the antiapoptotic X-linked inhibitor of apoptosis (XIAP) and Bcl-xL, and the proapoptotic caspase-1, were determined. These genes play central roles in neuronal cell apoptosis. Methods: Dark-adapted BALB/cJ mice aged 4- to 8-weeks old were exposed to a green light (3.1 to 3.5 Klux) for 1, 3, 6, 9, or 12 hrs and killed immediately after exposure. Initiation of NF-kB activation was determined by the increased phosphorylated IkBa (pIkBa) determined by Western blotting and the activation of NF-kB activation was demonstrated by NF-kB p65 immunolabeling. The time courses of expression of XIAP, Bcl-xL, and caspase-1 were determined by Western blotting. Immunohistochemistry for caspase-1 was also performed. In Western blotting, we used whole retinas and dissected photoreceptor cells from the retinas to obtain photoreceptor-specific information. The co-localization of NFkB p65 with TUNEL was noted by double labeling photoreceptor cells. Results: In Western blotting, the level of pIkBa increased at 1 hr of light exposure and maintained an elevated level by 12 hrs. In parallel, the expression levels of XIAP and Bcl-xL increased at 1, 3, 6, 9, or 12 hrs. In contrast, the amount of caspase-1 did not increase until after 6 hrs of light exposure. In immunohistochemical studies, a few photoreceptor cells with caspase-1 immunolabeling were observed at 3 hrs of light exposure and became marked at 6 hrs. The time course of the increased expression of caspase-1 in photoreceptor cells paralleled that of the increased number of TUNEL-positive photoreceptor cells. The co-localization of NF-kB p65 immunoreactivity and TUNEL was observed in photoreceptor cells at 12 hrs of light exposure. Conclusions: These findings suggest that 1) NF-kB plays an early anti-apoptotic role and a later pro-apoptotic role in light-induced photoreceptor degeneration, and 2) light-induced photoreceptor cell death occurs by an NF-kB / caspase-1 mediated pathway.
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