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NF‐κB activation mechanism of 4‐hydroxyhexenal via NIK/IKK and p38 MAPK pathway
Author(s) -
Je Jeong Hwan,
Lee Ji Young,
Jung Kyung Jin,
Sung Bokyung,
Go Eun Kyung,
Yu Byung Pal,
Chung Hae Young
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.04.037
Subject(s) - mapk/erk pathway , kinase , p38 mitogen activated protein kinases , transactivation , iκb kinase , phosphorylation , chemistry , nf κb , microbiology and biotechnology , protein kinase a , mitogen activated protein kinase , signal transduction , biochemistry , biology , transcription factor , gene
4‐Hydroxyhexenal (HHE) is known to affect redox balance during aging, included are vascular dysfunctions. To better understand vascular abnormality through the molecular alterations resulting from HHE accumulation in aging processes, we set out to determine whether up‐regulation of mitogen‐activated protein kinase (MAPK) by HHE is mediated through nuclear factor kappa B (NF‐κB) activation in endothelial cells. HHE induced NF‐κB activation by inhibitor of κB (IκB) phosphorylation via the IκB kinase (IKK)/NF‐κB inducing kinase (NIK) pathway. HHE increased the activity of p38 MAPK and extracellular signal regulated kinase (ERK), but not c‐jun NH 2 ‐terminal kinase, indicating that p38 MAPK and ERK are closely involved in HHE‐induced NF‐κB transactivation. Pretreatment with ERK inhibitor PD98059, and p38 MAPK inhibitor SB203580, attenuated the induction of p65 translocation, IκB phosphorylation, and NF‐κB luciferase activity. These findings strongly suggest that HHE induces NF‐κB activation through IKK/NIK pathway and/or p38 MAPK and ERK activation associated with oxidative stress in endothelial cells.