A nuclear factor-kappaB inhibitor BAY 11-7082 suppresses endothelin-1 production in cultured vascular endothelial cells.
BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB), which prevents a step of the phosphorylation of inhibitory protein IkappaB bound to NF-kappaB, suppressed basal and tumor necrosis factor (TNF)-alpha-induced prepro endothelin (ET)-1 mRNA expression and NF-kappaB activation in cultured vascular endothelial cells. BAY 11-7082 significantly decreased basal and TNF-alpha-induced ET-1 release from endothelial cells. These results indicate that the inhibition of NF-kappaB activation contributes to the suppressive effect of BAY 11-7082 on ET-1 gene expression and ET-1 release, thereby suggesting that NF-kappaB plays an important role in the regulation of ET-1 production.
Ohkita
Mamoru
M
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Japan.
Takaoka
Masanori
M
Shiota
Yasuko
Y
Nojiri
Rumi
R
Sugii
Masato
M
Matsumura
Yasuo
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001011:Aorta; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009570:Nitriles; D009930:Organic Chemicals; D012333:RNA, Messenger / Q000096:biosynthesis; D013450:Sulfones; D013552:Swine
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000970:Antineoplastic Agents; D019332:Endothelin-1; D016328:NF-kappa B; D009570:Nitriles; D009930:Organic Chemicals; D012333:RNA, Messenger; D013450:Sulfones