title: Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo.
abstract: To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.
authors.affiliation: Department of Pathology, Microbiology and Immunology/Oncology Institute, Loyola University Chicago, IL, USA.
authors.forename: Yasser E
authors.initials: YE
authors.lastname: Elassiuty
authors.forename: Jared
authors.initials: J
authors.lastname: Klarquist
authors.forename: Jodi
authors.initials: J
authors.lastname: Speiser
authors.forename: Randa M
authors.initials: RM
authors.lastname: Yousef
authors.forename: Abdelaziz A
authors.initials: AA
authors.lastname: El Refaee
authors.forename: Nahla S
authors.initials: NS
authors.lastname: Hunter
authors.forename: Olfat G
authors.initials: OG
authors.lastname: Shaker
authors.forename: Mohan
authors.initials: M
authors.lastname: Gundeti
authors.forename: Ludmila
authors.initials: L
authors.lastname: Nieuweboer-Krobotova
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008544:Melanocytes / Q000201:enzymology* / Q000473:pathology* / Q000528:radiation effects; D018384:Oxidative Stress; D011701:PUVA Therapy; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects; D014820:Vitiligo / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*
chemical_list: D000975:Antioxidants; D012313:RNA; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2