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HZ Malina, B Frueh; Xanthurenic Acid Induces Apoptosis in Human Lens Epithelial Cells, Retinal Pigment Epithelium Cells and Retinal Astrocytes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2410.
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Purpose: Xanthurenic acid is an endogenous substance formed during tryptophan degradation. We previously observed an activation of caspase-8,-9 and -3 in human retinal pigment epithelium and smooth muscle cells in the presence of xanthurenic acid. The observed cleavage of caspase-3 substrates leads to the cell death. We also showed that xanthurenic acid leads to caspase-8 activation and BID cleavage, and the truncated BID is translocated into mitochondria. (see: biomedcentral.com in: Biology Journals, Physiology, Malina et al.) Methods: The primary cultures of lens cells were prepared from a post-mortem human eye after transplantation of the cornea (Eye Bank, Inselspital, Bern). Cells were grow in the MEM medium with 10% of fetal calf serum. Primary and secondary antibodies were from Santa Cruz and Molecular Probes. Western blot analysis and immunofluorescence microscopy were used in the study. Results: The present studies were performed in human primary cells cultures (retinal astrocytes, retinal pigment epithelium, and lens epithelial cells) and in vitro using isolated live rat mitochondria. Here, we report that xanthurenic acid is involved in a regulation of Ca2+ and cytochrome C release from mitochondria. We observed a translocation of Bax from cytoplasm to mitochondria. A modification of Bax folding in the presence of xanthurenic acid seems to be involved in the induction of mitochondrial permeability transition pores. Xanthurenic acid leads also to translocation of Apoptosis Inducing Factor from mitochondria into nucleus. Conclusion: Our data show that xanthurenic acid may be a signaling molecule for intrinsic pathways of apoptosis.
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