Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage
نویسندگان
چکیده
منابع مشابه
Indirect antioxidant protection against photooxidative processes initiated in retinal pigment epithelial cells by a lipofuscin pigment.
Oxidative mechanisms are considered to contribute to the aging changes in retinal pigment epithelial (RPE) cells that underlie the pathogenesis of age-related macular degeneration. An important source of oxidative damage is likely to be the photoreactive pigments that progressively accumulate and constitute the lipofuscin of retinal pigment epithelial cells. Evidence for a link between RPE lipo...
متن کاملInflammasome priming increases retinal pigment epithelial cell susceptibility to lipofuscin phototoxicity by changing the cell death mechanism from apoptosis to pyroptosis.
Progressive death of retinal pigment epithelium (RPE) cells is a hallmark of age-related macular degeneration (AMD), the leading cause of blindness in all developed countries. Photooxidative damage and activation of the NLRP3 inflammasome have been suggested as contributing factors to this process. We investigated the effects of inflammasome activation on oxidative damage-induced RPE cell death...
متن کاملComplement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium.
Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). Several lines of investigation also indicate that bis-retinoid pigments, such as A2E, that accumulate as lipofuscin in retinal pigment epithelial (RPE) cells, contribute to the disease process. In an investigation of a poten...
متن کاملInhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E
In this study, we show augmented autophagy in the retinal pigment epithelial cell line ARPE-19 when cultured in the presence of the lipofuscin pigment A2E. A2E alone does not induce RPE cell death, but cell death was induced in the presence of A2E with the autophagy inhibitor 3-methyladenine (3MA), with a concomitant increase in the generation of mitochondrial reactive oxygen species. On the ot...
متن کاملComplement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation.
Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of com...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2015
ISSN: 0021-9258
DOI: 10.1074/jbc.m115.671180