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J Biol Chem. 1999 Feb 5;274(6):3734-43.

Photo-oxidative stress down-modulates the activity of nuclear factor-kappaB via involvement of caspase-1, leading to apoptosis of photoreceptor cells.

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  • 1Department of Anatomy and Cell Biology, North Texas Eye Research Institute at University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.

Abstract

The mechanisms of photoreceptor cell death via apoptosis, in retinal dystrophies, are largely not understood. In the present report we show that visible light exposure of mouse cultured 661W photoreceptor cells at 4.5 milliwatt/cm2 caused a significant increase in oxidative damage of 661W cells, leading to apoptosis of these cells. These cells show constitutive expression of nuclear factor-kappaB (NF-kappaB), and light exposure of photoreceptor cells results in lowering of NF-kappaB levels in both the nuclear and cytosolic fractions in a time-dependent manner. Immunoblot analysis of IkappaBalpha and p50, and p65 (RelA) subunits of NF-kappaB, suggested that photo-oxidative stress results in their depletion. Immunocytochemical studies using antibody to RelA subunit of NF-kappaB further revealed the presence of this subunit constitutively both in the nucleus and cytoplasm of the 661W cells. Upon exposure to photo-oxidative stress, a depletion of the cytoplasmic and nuclear RelA subunit was observed. The depletion of NF-kappaB appears to be mediated through involvement of caspase-1. Furthermore, transfection of these cells with a dominant negative mutant IkappaBalpha greatly enhanced the kinetics of down modulation of NF-kappaB, resulting in a faster photo-oxidative stress-induced apoptosis. Taken together, these studies show that the presence of NF-kappaB RelA subunit in the nucleus is essential for protection of photoreceptor cells against apoptosis mediated by an oxidative pathway.

PMID:
9920926
[PubMed - indexed for MEDLINE]
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