title: Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet irradiation-induced damage by modulating cell signaling pathways.
abstract: Selenoprotein H (SelH) is one of the 25 so far identified selenoproteins. Selenoproteins may function as antioxidants, heavy metal antidotes, and neural survival factors. Previous studies have shown that overexpression of SelH in HT22 cells protected the cells from UVB irradiation-induced death by reducing superoxide formation. The objective of this study was to determine the effects of SelH on cell signaling pathways after UVB irradiation. We exposed both human SelH- and vector-transfected HT22 cells to UVB irradiation and collected samples at 5 and 17 h of recovery. Cell viability was assessed, as well as protein levels of caspase-3, -8, -9, apoptosis-inducing factor (AIF), P53, nuclear respiratory factor-1 (NRF-1) and heat shock protein 40 (HSP40). Mitochondrial membrane potential was determined by flow cytometry. Overexpression of SelH protected cells against UVB-induced injury by blockade of the mitochondria-initiated cell death pathway, prevention of mitochondrial membrane depolarization, and suppression of the increase of p53. Furthermore, overexpression of SelH increased levels of NRF-1, an antioxidant, and HSP40, a protein chaperone that repairs denatured protein. We conclude that SelH protects neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, by preventing mitochondrial depolarization, and by promoting cell survival pathways.
authors.affiliation: Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, 302 East Lawson Street, Durham, NC 27707, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Mendelev
authors.forename: Sam
authors.initials: S
authors.lastname: Witherspoon
authors.forename: P Andy
authors.initials: PA
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism / Q000528:radiation effects; D053453:Caspase 9 / Q000378:metabolism / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D051336:Mitochondrial Membranes / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000528:radiation effects*; D051266:Nuclear Respiratory Factor 1 / Q000096:biosynthesis / Q000235:genetics; D051140:Selenoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; D050956:HSP40 Heat-Shock Proteins; D051266:Nuclear Respiratory Factor 1; D051140:Selenoproteins; D016159:Tumor Suppressor Protein p53; C519118:selenoprotein H, human; D053148:Caspase 3; D053453:Caspase 9