Ebselen inhibits tumor necrosis factor-α-induced c-Jun N-terminal kinase activation and adhesion molecule expression in endothelial cells

Oxidative Stress and Novel Antioxidant Approaches to Reduce Diabetic Complications

“…Our in vitro data showed that H 2 O 2 -induced upregulation of TNF-Ǐ was reduced by ebselen. Our results support previous findings that ebselen inhibits TNF-Ǐ-induced pro-inflammatory responses in endothelial cells (Yoshizumi et al 2004) and other cell types (Sharma et al 2008;Tewari et al 2009). We also investigated the effects of ebselen on H 2 O 2 -mediated phosphorylation of JNK, a kinase involved in the activation of the transcription factor, AP-1.…”

Anticoagulant activities of curcumin and its derivative

“…Based on the results that curcumin could inhibit generation of FXa and thrombin, the anticoagulant activity of curcumin was initiated from the inhibition of the penultimate and final enzyme in the blood clotting cascade. TNF-α has been known to activate JNK, NF-κB, and ERK in human endothelial cells (33)(34)(35). Here, we used a JNK (SP600125), NF-κB (emodin), and ERK (PD98059) inhibitors to define the molecular target of curcumin.…”

The role of peroxidases in the pathogenesis of atherosclerosis

“…Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) activate NF-κB and activator protein-1 (AP-1), which regulate genes involved in the expression of adhesion molecules on activated endothelial cells (52)(53)(54). TNF-α also induces expression of adhesion molecules associated with the TNF receptor-associated factor 2 (TRAF2)/apoptosis signal-regulated kinase 1/stress-activated protein kinase ERK kinase 1/c-Jun N-terminal kinase (JNK) signaling pathway (55). We confirmed that H2O2 and NF-κB signaling are important for the TNF-α-mediated expression of VCAM-1 and ICAM-1 using antioxidants and inhibitors of NF-κB and MAPK in mouse aortic endothelial cells (56).…”

“…Ebselen, a seleno-organic compound Gpx1-mimetic, inhibits TNF-α-induced JNK activation following TRAF2/apoptosis signal-regulated kinase 1 complex formation and phosphorylation of stress-activated protein kinase ERK kinase 1, and downregulates TNF-α-induced expression of VCAM-1 and ICAM-1 via inactivation of AP-1 and NF-κB (55). Results from an in vivo model showed that ebselen produces a site-specific anti-atherogenic effect by reducing levels of nitrotyrosine, Nox2, and vascular endothelial growth factor (100).…”