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(‐)Epigallocatechin gallate and quercetin differentially enhance survival signaling in response to oxidized LDL‐induced human endothelial apoptosis
Author(s) -
Choi JungSuk,
Kang YoungHee
Publication year - 2006
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.20.5.lb101
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , phosphorylation , apoptosis , chemistry , microbiology and biotechnology , quercetin , signal transduction , cytoprotection , downregulation and upregulation , cancer research , biochemistry , biology , antioxidant , gene
Oxidized low‐density lipoprotein (oxLDL) is believed to play an important role as a triggering molecule in the early stages of atherosclerosis. We have shown the (‐)epigallocatech gallate, quercetin and hesperitin among flavonoids inhibit oxLDL‐induced endothelial apoptosis (Br. J Nutrition, 93:581–591. 2005). We tested whether these flavonoids can manipulate MAPK‐responsive multiple death/survival signaling pathways that converge at the level of transcriptional regulation. Although the mechanisms involved in this activation of oxLDL have been fully elucidated, oxLDL activates several MAPK including the ERK, JNK and p38 MAPK. As expected, Western blot data revealed that oxLDL upregulated activation of JNK and p38 MAPK, which was rapidly reversed by (‐)epigallocatech gallate and hesperitin. On the other hand, quercetin down‐regulated oxLDL‐induced phosphorylation of p38 MAPK within 30 min but did not inhibit oxLDL‐induced the phosphorylation of JNK induced by oxLDL. These results suggest that the inhibition of oxLDL‐induced apoptosis by (‐)epigallocatechingallate and hespritin are mediated at least in part viaan activation of JNK and/or p38 MAPK, and that the cytoprotection of quercetin appears to be p38 MAPK‐responsive. Thus, our results provide new insights into the relativecontributions of JNK and p38 MAPK to the survival signaling of (‐) epigallocatechingallate, quercetin and hesperitin following oxidized LDL injury. Supported by the Korea Research Foundation (2004‐041‐C00439).