The Glutaredoxin/Glutathione System Modulates NF-κB Activity by Glutathionylation of p65 in Cinnamaldehyde-Treated Endothelial Cells

摘要: Reversible protein glutathionylation is an important posttranslational modification that provides protection against oxidation. In endothelial cells (ECs), cinnamaldehyde electrophilic compound can increase the intracellular glutathione (GSH) levels or reactive oxygen species (ROS) production depending on treatment duration. ECs treated with GSH and H(2)O(2) show increased sulfhydryl modifications of p65 subunit nuclear factor kappa-light-chain-enhancer activated B (NF-kappaB), which are responsible for NF-kappaB inactivation, also a block in TNF-alpha-induced translocation inter-cellular adhesion molecule-1 (ICAM-1) expression. our current study, we find induces inhibits ICAM-1 expression within 12 h treatment. Our analyses reveal suppressed by synthesis inhibitor, buthionine sulfoximine (BSO), further observed inhibitory effects BSO. NF-E2-related factor-2 small interfering RNA (siRNA) molecules not only inhibit glutamate-cysteine ligase catalytic (GCLC) modifier (GCLM) induction increases but abolish cinnamaldehyde-induced its effects. The gene activity glutaredoxin-1 (Grx-1), catalyzes formation protein-glutathione mixed disulfides (protein-SSG), were found to be after A knock down endogenous Grx-1 siRNA pretreatment inhibitor activity, CdCl(2), abolishes p65-SSG formation. addition, blocks inhibition expression, suggesting this enzyme involved cinnamaldehyde-mediated inhibition. results thus indicate GSH/Grx-1-dependent likely inactivation enhanced upon TNF-alpha-treated ECs.