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Protective effects of quercetin against oxidized LDL‐induced apoptosis through p38 MAP kinase‐dependent and JAK‐responsive pathways in human endothelial cells
Author(s) -
Choi Jung Suk,
Li Jing,
Kang Young Hee
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.890.16
Subject(s) - quercetin , p38 mitogen activated protein kinases , apoptosis , mapk/erk pathway , phosphorylation , chemistry , microbiology and biotechnology , stat3 , kinase , signal transduction , western blot , cancer research , biology , biochemistry , antioxidant , gene
OxLDL is present in atherosclerotic lesions and has been proposed to play an important role in atherogenesis. The present study elucidated multiple MAPK‐responsive death/survival signaling pathways, through which quercetin exerted anti‐apoptosis in endothelial cells exposed to oxLDL. Quercetin substantially diminished the oxLDL‐induced cytotoxicity and DCF staining, suggesting the inhibition of accumulation of oxLDL‐triggered ROS and consequent apoptosis. Additionally, oxLDL induced p53 activation for the Bax translocation and the luciferase activity of p53, which induction was strikingly down‐regulated by quercetin. The Western blot data identified that quercetin at ≤ 10 μM promptly attenuated phosphorylation of ASK‐1, p38MAPK but not JNK, and its downstream c‐myc evoked by oxLDL. Furthermore, this study also attempted to explore JAK2/STAT3 activation in oxLDL‐induced endothelial apoptosis. It was found that quercetin rapidly attenuated the phosphorylation of JAK2 and STAT3 within 30 min. Our findings suggest that the interplay between p38MAPK and is involved in dietary quercetin protection against oxLDL through hampering p38 MAPK‐dependent pathways involving the activation of JAK2. Thus, quercetin may act as anti‐atherogenic agents blocking oxLDL‐induced endothelial apoptosis. Grant Funding Source : KRF‐2003‐041‐C20338 from Korea Research Foundation and Brain Korea 21.