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

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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Kivelä AM,Mäkinen PI,Jyrkkänen HK,Mella-Aho E,Xia Y,Kansanen E,Leinonen H,Verma IM,Ylä-Herttuala S,Levonen AL

doi

10.1016/j.atherosclerosis.2010.07.015

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

122-8

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(10)00557-5

journal_volume

213

pub_type

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