Tanshinone II-A inhibits oxidized LDL-induced LOX-1 expression in macrophages by reducing intracellular superoxide radical generation and NF-κB activation

Xu, Suowen, Liu, Zhiping, Huang, Yan, Le, Kang, Tang, Futian, Huang, Heqing, Ogura, Sayoko, Little, Peter J., Shen, Xiaoyan and Liu, Peiqing (2012) Tanshinone II-A inhibits oxidized LDL-induced LOX-1 expression in macrophages by reducing intracellular superoxide radical generation and NF-κB activation. Translational Research, 160 2: 114-124. doi:10.1016/j.trsl.2012.01.008


Author Xu, Suowen
Liu, Zhiping
Huang, Yan
Le, Kang
Tang, Futian
Huang, Heqing
Ogura, Sayoko
Little, Peter J.
Shen, Xiaoyan
Liu, Peiqing
Title Tanshinone II-A inhibits oxidized LDL-induced LOX-1 expression in macrophages by reducing intracellular superoxide radical generation and NF-κB activation
Formatted title
Tanshinone II-A inhibits oxidized LDL-induced LOX-1 expression in macrophages by reducing intracellular superoxide radical generation and NF-κB activation
Journal name Translational Research   Check publisher's open access policy
ISSN 1931-5244
1878-1810
Publication date 2012-08
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.trsl.2012.01.008
Open Access Status Not yet assessed
Volume 160
Issue 2
Start page 114
End page 124
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher Mosby
Language eng
Formatted abstract
Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1), a novel scavenger receptor highly expressed in human and experimental atherosclerotic lesions, is responsible for the uptake of oxLDL in vascular cells. We demonstrated previously that Tanshinone II-A (Tan), a pharmacologically active compound extracted from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge, inhibits atherogenesis in hypercholesterolemic rats, rabbits, and apolipoprotein-E deficient (ApoE-/-) mice. However, the precise mechanism by which Tan protects against atherogenesis remains to be elucidated. Therefore, we hypothesized that Tan can suppress the uptake of oxLDL by diminishing the expression of LOX-1 via suppression of NF-κB signaling pathway, thereby contributing to reduced macrophage foam cell formation. In cultured murine macrophages, oxLDL induced LOX-1 expression at the mRNA and protein levels, was abrogated by addition of Tan or pyrrolidinedithiocarbamic acid ammonium salt (PDTC), a widely used inhibitor of NF-κB, suggesting the involvement of NF-κB. Tan also reduced LOX-1 expression in atherosclerotic lesions of ApoE-/- mice fed a high cholesterol diet. Mechanistically, Tan suppressed the nuclear translocation of NF-κB P65 subunit and phosphorylation of IκB-α induced by oxLDL. Electrophoretic mobility shift assay (EMSA) demonstrated that Tan inhibited the nuclear protein binding to NF-κB consensus sequence. Functionally, we observed that Tan inhibited DiI-oxLDL uptake by macrophages in a fashion similar to that produced by LOX-1 neutralizing antibody. Our current findings reveal a novel mechanism by which Tan protects against atherogenesis and shed new light on the potential therapeutic application of Tan to the treatment and prevention of atherosclerotic cardiovascular diseases.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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