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Lu, T.T.* ; Heyne, S.* ; Dror, E.* ; Casas, E.* ; Leonhardt, L.* ; Boenke, T.* ; Yang, C.-H.* ; Sagar* ; Arrigoni, L.* ; Dalgaard, K.* ; Teperino, R. ; Enders, L.* ; Selvaraj, M.* ; Ruf, M.* ; Raja, S.J.* ; Xie, H.* ; Boenisch, U.* ; Orkin, S.H.* ; Lynn, F.C.* ; Hoffman, B.G.* ; Grün, D.* ; Vavouri, T.* ; Lempradl, A.M.* ; Pospisilik, J.A.*

The polycomb-dependent epigenome controls beta cell dysfunction, dedifferentiation, and diabetes.

Cell Metab. 27, 1294-1308.e7 (2018)
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Creative Commons Lizenzvertrag
Skin affections after sulfur mustard (SM) exposure include erythema, blister formation and severe inflammation. An antidote or specific therapy does not exist. Anti-inflammatory compounds as well as substances counteracting SM-induced cell death are under investigation. In this study, we investigated the benzylisoquinoline alkaloide berberine (BER), a metabolite in plants like berberis vulgaris, which is used as herbal pharmaceutical in Asian countries, against SM toxicity using a well-established in vitro approach. Keratinocyte (HaCaT) mono-cultures (MoC) or HaCaT/THP-1 co-cultures (CoC) were challenged with 100, 200 or 300 mM SM for 1 h. Post-exposure, both MoC and CoC were treated with 10, 30 or 50 mu M BER for 24 h. At that time, supernatants were collected and analyzed both for interleukine (IL) 6 and 8 levels and for content of adenylate-kinase (AK) as surrogate marker for cell necrosis. Cells were lysed and nucleosome formation as marker for late apoptosis was assessed. In parallel, AK in cells was determined for normalization purposes. BER treatment did not influence necrosis, but significantly decreased apoptosis. Anti-inflammatory effects were moderate, but also significant, primarily in CoC. Overall, BER has protective effects against SM toxicity in vitro. Whether this holds true should be evaluated in future in vivo studies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter β cells de-differentiation type 2 diabetes diabetes Polycomb epigenetic chromatin cell identity complex diseases Eed; Cell-line Thp-1; In-vitro; Hacat Keratinocytes; Alkaloid Berberine; Dendritic Cells; Injury; Skin; Sensitization; Expression; Toxicity
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Zeitschrift Cell Metabolism
Quellenangaben Band: 27, Heft: 6, Seiten: 1294-1308.e7 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-501900-069
DOI 10.1016/j.cmet.2018.04.013
WOS ID WOS:000434480000015
Scopus ID 85046683882
Erfassungsdatum 2018-05-24
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