title: Effects of non-toxic zinc exposure on human epidermal keratinocytes.
abstract: Zinc is an essential microelement; its importance to the skin is highlighted by the severe skin symptoms in hereditary or acquired zinc deficiency, by the improvement of several skin conditions using systemic or topical zinc preparations and by the induced intracellular zinc release upon UVB exposure, which is the main harmful environmental factor to the skin. Understanding the molecular background of the role of zinc in skin may help gain insight into the pathology of skin disorders and provide evidence for the therapeutic usefulness of zinc supplementation. Herein, we studied the effects of zinc chloride (ZnCl2) exposure on the function of HaCaT keratinocytes, and the results showed that a non-toxic elevation in the concentration of extracellular zinc (100 μM) facilitated cell proliferation and induced significant alterations in the mRNA expression of NOTCH1, IL8, and cyclooxygenase-2. In addition, increased heme oxygenase-1 (HMOX1) expression and non-toxic generation of superoxide were detected in the first 4 h. Regarding the effects on the UVB-induced toxicity, although the level of cyclobutane pyrimidine dimers in the keratinocytes pre-treated with zinc for 24 h was reduced 3 h after UVB irradiation, significantly enhanced superoxide generation was observed 10 h after UVB exposure in the zinc pre-exposed cells. The overall survival was unaffected; however, there was a decrease in the percentage of early apoptotic cells and an increase in the percentage of late apoptotic plus necrotic cells. These results suggest that the exposure of human keratinocytes to non-toxic concentrations of ZnCl2 impacts gene expression, cell proliferation and the responses to environmental stress in the skin. It would be important to further examine the role of zinc in skin and further clarify whether this issue can affect our thinking regarding the pathogenesis of skin diseases.
authors: Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary. remenyik@med.unideb.hu.
authors: Eszter
authors: E
authors: Emri
authors: Edit
authors: E
authors: Miko
authors: Péter
authors: P
authors: Bai
authors: Gábor
authors: G
authors: Boros
authors: Georgina
authors: G
authors: Nagy
authors: Dávid
authors: D
authors: Rózsa
authors: Tamás
authors: T
authors: Juhász
authors: Csaba
authors: C
authors: Hegedűs
authors: Irén
authors: I
authors: Horkay
authors: Éva
authors: É
authors: Remenyik
authors: Gabriella
authors: G
authors: Emri
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D000078404:Epidermal Cells; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D008668:Metallothionein / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014466:Ultraviolet Rays; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D011740:Pyrimidine Dimers; D013481:Superoxides; D008668:Metallothionein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D015032:Zinc