Abstract Title:

Sulforaphane inhibits endothelial lipase expression through NF-κB in endothelial cells.

Abstract Source:

Atherosclerosis. 2010 Nov;213(1):122-8. Epub 2010 Jul 21. PMID: 20688330

Abstract Author(s):

Annukka M Kivelä, Petri I Mäkinen, Henna-Kaisa Jyrkkänen, Eero Mella-Aho, Yifeng Xia, Emilia Kansanen, Hanna Leinonen, Inder M Verma, Seppo Ylä-Herttuala, Anna-Liisa Levonen

Article Affiliation:

The Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Neulaniementie 2, FIN-70211 Kuopio, Finland.

Abstract:

OBJECTIVE: Endothelial lipase (EL) is a new member of triacylglycerol lipase family that has been shown to decrease high-density lipoprotein (HDL) cholesterol levels leading to increased risk of atherosclerosis. Its expression is increased during inflammation and by inflammatory cytokines. Sulforaphane (SFN) is a naturally occurring isothiocyanate present in cruciferous vegetables that has antioxidant and anti-inflammatory effects. Nuclear factor (NF)-κB is one of the molecular targets for SFN-mediated protective effects. Our aim was therefore to assess whether SFN could impact on EL expression via modulation of NF-κB pathway. METHODS AND RESULTS: Quantitative PCR and Western blot results demonstrated that SFN inhibited tumor necrosis factor (TNF)-α-mediated induction of EL in human umbilical vein endothelial cells (HUVEC). Lentiviral transduction of HUVEC with mutated form of IκB-α (IκBM) as well as silencing of NF-κB subunit p65 using RNA interference revealed that TNF-α-mediated induction of EL is mediated through NF-κB pathway.In addition, a total of five NF-κB binding sites were found in LIPG gene, which encodes EL. SFN inhibited binding of NF-κB to these sites analyzed by chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). SFN also inhibited TNF-α mediated phosphorylation of IκB kinase (IKK) 1/2 and IκB-α. CONCLUSIONS: Collectively, these results indicate that SFN inhibits EL expression via inhibition of NF-κB which may have a beneficial effect on HDL cholesterol levels.

Study Type : In Vitro Study

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