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Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants
Author(s) -
Spiecker Martin,
Darius Harald,
Kaboth Katharina,
Hübner Felix,
Liao James K.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.6.732
Subject(s) - mg132 , iκbα , phosphorylation , iκb kinase , nitric oxide , nf κb , cell adhesion molecule , biology , microbiology and biotechnology , tumor necrosis factor alpha , cell adhesion , proteasome inhibitor , biochemistry , proteasome , signal transduction , immunology , cell , endocrinology
Abstract Although nitric oxide (NO) and antioxidants inhibit adhesion molecule expression, their inhibitory effects on nuclear factor κB (NF‐κB) activation may differ. The NO donors, but not 8‐bromo‐cGMP, decreased tumor necrosis factor α (TNF‐α)‐induced VCAM‐1, ICAM‐1, and E‐selectin expression by 11‐70%. In contrast, NAC completely abolished VCAM‐1 and E‐selectin expression and decreased ICAM‐1 expression by 56%. Gel shift assays demonstrate that NF‐κB activation was inhibited by both NO and antioxidants. The activation of NF‐κB involves the phosphorylation and degradation of its cytoplasmic inhibitor IκB‐α by 26S proteasomes. The 26S proteasome inhibitor MG132 prevented the degradation of phosphorylated IκB‐α. NAC inhibited IκB kinase (IKK) activity and prevented IκB‐α phosphorylation and degradation. In contrast, NO did not inhibit IKK activity, IκB‐α phosphorylation, or IκB‐α degradation. However, NO, but not antioxidants, induced IκB‐α promoter activity. The inhibitory effects of NO on adhesion molecule expression, therefore, differs from that of antioxidants in terms of the mechanism by which NF‐κB is inactivated. J. Leukoc. Biol . 63: 732–739; 1998.