title: Brusatol inhibits the response of cultured beta-cells to pro-inflammatory cytokines in vitro.
abstract: Brusatol is a natural terpenoid that is capable of inducing a variety of biological effects. We presently report that this substance dramatically improves beta-cell survival when exposed to pro-inflammatory cytokines (IL-1β and IFNγ) in vitro. This was observed in insulin producing rat (RIN-5AH), mouse (βTC6) and human (EndoC-βH1) beta-cell lines. Brusatol prevented beta-cell oxidative stress in response to cytokines and counteracted induction of iNOS on the protein level. Brusatol, however, block neither the cytokine-induced increase of iNOS mRNA, nor NF-κB activation, suggesting that inhibition of iNOS protein expression relies on posttranscriptional mechanism. This indicates that brusatol acts via a novel protective pathway, which may represent a more promising way of improving beta-cell function and survival.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedicum, SE-751 23 Uppsala, Sweden; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 119991 Moscow, Russia. Electronic address: kyril.turpaev@yahoo.com.
authors.forename: Kyril
authors.initials: K
authors.lastname: Turpaev
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedicum, SE-751 23 Uppsala, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000502:physiology*; D017931:DNA Primers; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D036702:Quassins / Q000494:pharmacology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D036702:Quassins; C020237:brusatol; D052247:Nitric Oxide Synthase Type II
keywords: Beta-cells; Brusatol; Cytokines; Oxidative stress; iNOS