NDLI: Polarized distribution of heme transporters in retinal pigment epithelium and their regulation in the iron-overload disease hemochromatosis.

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Polarized distribution of heme transporters in retinal pigment epithelium and their regulation in the iron-overload disease hemochromatosis.

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Polarized distribution of heme transporters in retinal pigment epithelium and their regulation in the iron-overload disease hemochromatosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Smith, Sylvia B. Martin, Pamela M. Ganapathy, Vadivel Reddy, Sushma K. Gnana-Prakasam, Jaya P. Veeranan-Karmegam, Rajalakshmi
Description	Country affiliation: United States Author Affiliation: Gnana-Prakasam JP ( Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia 30912, USA.)
Abstract	PURPOSE: FLVCR, BCRP, and PCFT/HCP-1 represent the three heme transporters identified thus far in mammalian cells, but there is very little known about their expression and regulation in the retina. In this study, the expression of these transporters in mouse retina and retinal pigment epithelium (RPE) and their regulation in the iron-overload disease hemochromatosis were examined. METHODS: The expression of FLVCR, BCRP, and PCFT in mouse retina and primary mouse RPE cells was studied by RT-PCR and immunofluorescence. Polarized localization of the transporters in RPE was studied by co-localization using a specific marker of the RPE apical membrane. Uptake of heme in primary RPE cells was determined using zinc-mesoporphyrin, a fluorescent heme analogue. The regulation of heme transporters by iron overload was studied in two genetic models of hemochromatosis (HFE-null mouse and HJV-null mouse) and in two nongenetic models of iron overload (cytomegalovirus infection and treatment with ferric ammonium citrate). RESULTS: All three heme transporters were expressed in the retina and RPE. In the RPE, the expression of FLVCR was restricted to the apical membrane, and the expression of BCRP and PCFT was restricted to the basolateral membrane. In all cases of iron overload, the expression of FLVCR and PCFT was upregulated and that of BCRP was downregulated. CONCLUSIONS: Hemochromatosis is associated not only with excessive accumulation of free iron in the retina and RPE but also with excessive accumulation of heme. Since heme is toxic at high levels, as is free iron, heme-induced oxidative damage may also play a role in hemochromatosis-associated retinal pathology.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.11-8264
Journal	Investigative Opthalmology & Visual Science
Issue Number	12
Volume Number	52
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2011-11-29
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Atp-binding Cassette Transporters Genetics Disease Models, Animal Gene Expression Regulation Physiology Hemochromatosis Membrane Transport Proteins Proton-coupled Folate Transporter Receptors, Virus Retinal Pigment Epithelium Metabolism Animals Blotting, Western Cells, Cultured Fluorescent Antibody Technique, Indirect Heme Herpesviridae Infections Iron Overload Metalloporphyrins Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Muromegalovirus Rna, Messenger Real-time Polymerase Chain Reaction Retina Research Support, N.i.h., Extramural Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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