title: Topical ceramides neither enhance UVB-induced apoptosis in normal human keratinocytes nor affect viability in UVB-irradiated reconstructed human epidermis.
abstract: Ceramides are the major lipid of lamellar sheets present in intercellular spaces of the stratum corneum contributing to epidermal barrier properties. Therefore, ceramides and their analogues have been studied for barrier enhancing and water-holding properties for decades. In vitro studies have indicated cytotoxic potential for cell-permeable ceramides thereby raising the question whether topical ceramide application might contribute to UVB-induced apoptosis. Phytosphingosine, N-hexanoyl-phytosphingosine and N-stearoylphytosphingosine (ceramide III) in concentrations ≤5 μm have been used for co-stimulation with low (160 J/m(2) ) or high (600 J/m(2) ) UVB doses in subconfluent basal and confluent differentiating keratinocytes. Significantly, increased caspase-3 activity was observed in basal keratinocytes irradiated with 600 J/m(2) UVB and in differentiating keratinocytes with both UVB doses. Co-stimulation with the named ceramides did not further increase (i) caspase-3 activity and (ii) nucleosomal fragmentation in differentiating keratinocytes. Moreover, co-stimulation with 1-mm ceramides did not further affect viability/lactate dehydrogenase release in UVB-irradiated reconstructed human epidermis corroborating the safety of these ceramides.
authors: IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors: Susanne
authors: S
authors: Grether-Beck
authors: Ingo
authors: I
authors: Felsner
authors: Tim
authors: T
authors: Koehler
authors: Mike
authors: M
authors: Farwick
authors: Peter
authors: P
authors: Lersch
authors: Anthony V
authors: AV
authors: Rawlings
authors: Jean
authors: J
authors: Krutmann
mesh_terms: D000287:Administration, Topical; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002518:Ceramides / Q000008:administration & dosage* / Q000737:chemistry; D004817:Epidermis / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D012867:Skin; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
chemical_list: D002518:Ceramides; C553174:N-stearoylphytosphingosine; D014867:Water; C505407:CASP3 protein, human; D053148:Caspase 3; C012491:phytosphingosine; D013110:Sphingosine
keywords: N-hexanoyl-phytosphingosine; apoptosis; ceramide III; human reconstructed epidermis; phytosphingosine; viability