Heme-mediated reactive oxygen species toxicity to retinal pigment epithelial cells is reduced by hemopexin
✍ Scribed by Richard C. Hunt; Indhira Handy; Ann Smith
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 639 KB
- Volume
- 168
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
Catalysis of the formation of reactive oxygen species (R02S) by low molecular weight complexes of iron has been implicated in several pathological conditions in the retina since photoreceptors and retinal pigment epithelial cells are likely to be especially sensitive to R0,S. Since protective proteins cannot cross the blood-retinal barrier, it is likely that the retina performs its own protective functions by synthesizing proteins that bind iron and nonprotein iron complexes, the major catalysts of ROzS generation. Investigations were carried out to determine whether pigment epithelial cells are themselves sensitive to iron-generated RO,S and whether apo-transferrin and apo-hemopexin, known to be made locally in the retina, can perform a protective function. In 5'Cr release assays, the toxicity of exogenous RO,S including hydrogen peroxide or superoxide (generated by xanthine oxidase/hypoxanthine) to human retinal pigment epithelial cells was inhibited by the iron chelators, desferrioxamine and apo-transferrin. Free but not protein-bound ferric iron and heme exacerbated the toxic effect. The toxic effect of heme was abolished by the heme-scavenging, extracellular antioxidant, apohemopexin, and also by exogenous bovine serum albumin. In addition, heme toxicity was inhibited by a 3 h preincubation of cells with either heme, apohemopexin, or heme-hemopexin 24 h prior to the toxicity assay. It is concluded, first, that toxic effects of iron and heme can be prevented by apo-transferrin or apo-hemoxpexin and, second, that exposure of RPE cells to free heme or hemopexin sets in motion a series of biochemical events resulting in protection against oxidative stress. It is probable that these include heme oxygenase induction.