Hemopexin in the human retina: protection of the retina against heme-mediated toxicity.
The existence of the blood-retinal barrier means that proteins that protect the retina from damage by reactive oxygen species must either be made locally or specifically transported across the barrier cells; however, such transepithelial transport does not seem to occur. Among the circulatory proteins that protect against iron-catalyzed production of free radicals are apo-transferrin, which binds ferric iron and has previously been shown to be made by cells of the neural retina (Davis and Hunt, 1993, J. Cell Physiol., 156:280-285), and the extracellular antioxidant, apo-hemopexin, which binds free heme (iron-protoporphyrin IX). Since hemorrhage and heme release can be important contributing factors in retinal disease, evidence of a hemopexin-based retinal protection system was sought. The human retina has been shown to contain apo-hemopexin which is probably synthesized locally since its mRNA can be detected in retinal tissue dissected from human donor eyes. It is likely that the retina contains a mechanism for the degradation of hemopexin-bound heme since the blood-retinal barrier also precludes the exit of heme-hemopexin from the retina. Retinal pigment epithelial cells have been found to bind and internalize heme-hemopexin in a temperature-dependent, saturable, and specific manner, analogous to the receptor-mediated endocytic system of hepatoma cells. Moreover, the binding of heme-hemopexin to the cells stimulates the expression of heme oxygenase-1, metallothionein-1, and ferritin.
Hunt
R C
RC
Department of Microbiology and Immunology, University of South Carolina School of Medicine, Columbia 29208, USA.
Hunt
D M
DM
Gaur
N
N
Smith
A
A
D001059:Apoproteins / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005293:Ferritins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006418:Heme / Q000633:toxicity*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D006466:Hemopexin / Q000378:metabolism*; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D013997:Time Factors
D001059:Apoproteins; D017931:DNA Primers; D012333:RNA, Messenger; D006418:Heme; D005293:Ferritins; D006466:Hemopexin; D008668:Metallothionein; D006419:Heme Oxygenase (Decyclizing)