title: Iron upregulates melanogenesis in cultured retinal pigment epithelial cells.
abstract: The purpose of our studies was to examine the relationship between iron and melanogenesis in retinal pigment epithelial cells, as prior observations had suggested that iron may promote melanogenesis. This relationship has potential clinical importance, as both iron overload and hyperpigmentation are associated with age-related macular degeneration (AMD). Human fetal retinal pigment epithelial cells and ARPE-19 cells were treated with iron in the form of ferric ammonium citrate, after which quantitative RT-PCR and electron microscopy were performed. Melanogenesis genes tyrosinase, tyrosinase-related protein 1, Hermansky-Pudlak Syndrome 3, premelanosome protein and dopachrome tautomerase were upregulated, as was the melanogenesis-controlling transcription factor, microphthalmia-associated transcription factor (MITF). Iron-treated cells had increased pigmentation and melanosome number. Multiple transcription factors upstream of MITF were upregulated by iron.
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Wolkow
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Section of Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bldg. 10, Rm. 10B04, MSC 1861, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Arvydas
authors.initials: A
authors.lastname: Maminishkis
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Alekseev
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Iacovelli
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Delu
authors.initials: D
authors.lastname: Song
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 305 Stellar-Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104, USA. Electronic address: jdunaief@mail.med.upenn.edu.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D005290:Ferric Compounds / Q000494:pharmacology*; D005865:Gestational Age; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008543:Melanins / Q000096:biosynthesis*; D020460:Melanosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics; D014442:Monophenol Monooxygenase / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D014019:Tissue Donors; D015854:Up-Regulation / Q000502:physiology*; D058951:gp100 Melanoma Antigen / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D005290:Ferric Compounds; C432680:HPS3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D058951:gp100 Melanoma Antigen; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C013531:ferric ammonium citrate
keywords: ARPE-19 cells; Human fetal retinal pigment epithelial cells; Iron; LEF 1; MITF; Melanosome; Retinal pigment epithelium