Peptidylarginine Deiminase Inhibitor Cl-Amidine Attenuates Cornification and Interferes with the Regulation of Autophagy in Reconstructed Human Epidermis
| Autor: | Paul R. Thompson, Hidenari Takahara, Laura Cau, Guy Serre, Michel Simon, Marie-Claire Méchin |
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| Přispěvatelé: | CCSD, Accord Elsevier, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Ibaraki University, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Keratinocytes Ornithine Arginine Mitochondrion Biochemistry chemistry.chemical_compound 0302 clinical medicine Protein-Arginine Deiminase Type 3 MESH: Protein-Arginine Deiminase Type 1 / antagonists & inhibitors Protein-Arginine Deiminase Type 1 MESH: Citrulline / metabolism [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Autophagy / drug effects MESH: Ornithine / analogs & derivatives Citrulline Cells Cultured MESH: Protein-Arginine Deiminase Type 3 / metabolism deimination MESH: Protein-Arginine Deiminase Type 1 / metabolism Citrullination Cell Differentiation MESH: Cell Differentiation / physiology Recombinant Proteins MESH: Keratinocytes Cell biology 030220 oncology & carcinogenesis [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Microscopy Electron Transmission MESH: Protein Processing Post-Translational / physiology MESH: Cells Cultured skin autophagy citrullination MESH: Epidermis / ultrastructure Primary Cell Culture Dermatology MESH: Epidermis / drug effects Article MESH: Ornithine / pharmacology MESH: Primary Cell Culture 03 medical and health sciences Downregulation and upregulation Microscopy Electron Transmission MESH: Arginine / metabolism Humans transitional cells Molecular Biology Corneocyte MESH: Humans Epidermis (botany) keratinocyte differentiation Autophagy MESH: Protein Processing Post-Translational / drug effects Cell Biology MESH: Cell Differentiation / drug effects MESH: Autophagy / physiology 030104 developmental biology chemistry post-translational modification MESH: Epidermis / physiology MESH: Protein-Arginine Deiminase Type 3 / antagonists & inhibitors MESH: Recombinant Proteins / metabolism Epidermis Protein Processing Post-Translational |
| Zdroj: | Journal of Investigative Dermatology Journal of Investigative Dermatology, 2019, 139 (9), pp.1889-1897.e4. ⟨10.1016/j.jid.2019.02.026⟩ Journal of Investigative Dermatology, Nature Publishing Group, 2019, 139 (9), pp.1889-1897.e4. ⟨10.1016/j.jid.2019.02.026⟩ J Invest Dermatol |
| ISSN: | 0022-202X 1523-1747 |
| DOI: | 10.1016/j.jid.2019.02.026⟩ |
| Popis: | International audience; Deimination, a post-translational modification catalyzed by a family of enzymes called peptidylarginine deiminases (PADs), is the conversion of arginine into citrulline residues in a protein. Deimination has been associated with numerous physiological and pathological processes. Our aim was to study its implication in the homeostasis of human epidermis, where three PADs are expressed, namely PAD1, 2, and 3. Three-dimensional reconstructed human epidermis (RHEs) were treated for 2 days with increased concentrations (0-800 μM) of Cl-amidine, a specific PAD inhibitor. Cl-amidine treatments inhibited deimination in a dose-dependent manner and were not cytotoxic for keratinocytes. At 800 μM , Cl-amidine was shown to reduce deimination by half, alter keratinocyte differentiation, decrease the number of corneocyte layers, significantly increase the number of transitional cells, induce clustering of mitochondria and of heterogeneous vesicles in the cytoplasm of granular keratinocytes, and upregulate the expression of autophagy proteins, including LC3-II, sestrin-2, and p62/SQSTM1. LC3 and PADs were further shown to partially co-localize in the upper epidermis. These results demonstrated that Cl-amidine treatments slow down cornification and alter autophagy in the granular layer. They suggest that PAD1 and/or PAD3 play a role in the constitutive epidermal autophagy process that appears as an important step in cornification. |
| Databáze: | OpenAIRE |
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