title: UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impairment of Proteasome and Enhanced Autophagic Activity.
abstract: In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibition of proteasomal degradation of damaged proteins and the activation of autophagosome formation are early events in UVB-induced senescence of HDFs, dependent on UVB-induced accumulation of reactive oxygen species. Our data suggest that autophagy is required for the establishment of the senescent phenotype in UVB-treated HDFs and that inhibition of autophagy is sufficient to change the cell fate from senescence to cell death by apoptosis. Studies in reconstructed skin equivalents revealed that UVB irradiation triggers hallmarks of autophagy induction in the dermal layer. These findings have potential implications for fundamental as well as translational research into skin aging, in particular photoaging.
authors: Institute for Biomedical Aging Research, Universität Innsbruck, Austria.
authors: Maria
authors: M
authors: Cavinato
authors: Institute for Biomedical Aging Research, Universität Innsbruck, Austria.
authors: Rafal
authors: R
authors: Koziel
authors: Department of Dermatology and Venerology, Medical University of Innsbruck, Austria.
authors: Nikolaus
authors: N
authors: Romani
authors: Christian Doppler Laboratory on Biotechnology of Skin Aging, Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences Vienna, Austria.
authors: Regina
authors: R
authors: Weinmüllner
authors: Institute for Biomedical Aging Research, Universität Innsbruck, Austria.
authors: Brigitte
authors: B
authors: Jenewein
authors: Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Austria.
authors: Martin
authors: M
authors: Hermann
authors: Department of Dermatology and Venerology, Medical University of Innsbruck, Austria.
authors: Sandrine
authors: S
authors: Dubrac
authors: Department of Dermatology and Venerology, Medical University of Innsbruck, Austria.
authors: Gudrun
authors: G
authors: Ratzinger
authors: Christian Doppler Laboratory on Biotechnology of Skin Aging, Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences Vienna, Austria.
authors: Johannes
authors: J
authors: Grillari
authors: Department of Dermatology and Venerology, Medical University of Innsbruck, Austria.
authors: Matthias
authors: M
authors: Schmuth
authors: Institute for Biomedical Aging Research, Universität Innsbruck, Austria.
authors: Pidder
authors: P
authors: Jansen-Dürr
mesh_terms: D001343:Autophagy / Q000528:radiation effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000528:radiation effects*; D015531:Radioimmunoprecipitation Assay; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015595:Skin Aging / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; Proteasome; Senescence; Skin aging; UVB