Involvement of proteasome in endothelin-1 production in cultured vascular endothelial cells

Japanese Journal of Pharmacology
Mamoru OhkitaYasuo Matsumura

Abstract

We examined whether the proteasome could regulate endothelin (ET)-1 production in vascular endothelial cells (ECs). A proteasome inhibitor N-benzyloxycarbonyl-Ile-Glu (O-t-Bu)-Ala-leucinal (PSI) significantly decreased ET-1 release from ECs by about 25% of the basal release. PSI also suppressed tumor necrosis factor (TNF)-alpha-induced ET-1 release from ECs in a dose-dependent manner. Similar inhibitory effects were observed using another proteasome inhibitor lactacystin, whereas a calpain inhibitor calpeptin had no apparent effect on ET-1 release. Furthermore, PSI significantly attenuated prepro ET-1 mRNA expression under basal and TNF-alpha-stimulated conditions. Electrophoretic mobility shift assay showed that proteasome inhibitors diminished TNF-alpha-stimulated nuclear factor-kappa B (NF-kappaB) activation in ECs. Pretreatment with antioxidants, pyrrolidine dithiocarbamate and alpha-lipoic acid, both of which are known to be suppressors of NF-kappaB activation, effectively attenuated basal and TNF-alpha-induced ET-1 release. Thus, a proteasome-dependent proteolytic pathway is at least partly involved in ET-1 production under basal conditions, and this proteolytic pathway seems to have a crucial role in ET-1 production enha...Continue Reading

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Citations

Feb 11, 2014·Antioxidants & Redox Signaling·Nicola Wilck, Antje Ludwig
Sep 22, 2009·Cardiovascular Research·Karl Stangl, Verena Stangl
Oct 23, 2013·Pharmacological Reports : PR·Magdalena DudekLidia Włodek
May 5, 2009·Life Sciences·Mario LorenzVerena Stangl
Feb 20, 2007·Nitric Oxide : Biology and Chemistry·Vladan P CokicAlan N Schechter
Jun 25, 2005·European Journal of Pharmacology·Hayato KurataYasuo Matsumura
Sep 11, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Mamoru OhkitaYasuo Matsumura
Feb 18, 2005·Journal of the American Society of Nephrology : JASN·Alejandro R ChadeLilach O Lerman
Jul 16, 2005·International Journal of Cardiovascular Interventions·Joerg HerrmannAmir Lerman

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