Figure 10.

Relationship between GPxs and the NF-κB pathway in the antiproliferation action of butyrate. In response to proatherogenic stimuli, ROS, including hydroperoxides and lipid peroxides, are produced, which activate the redox-sensitive NF-κB signal cascade leading to the expression of target genes. Treatment of VSMC with butyrate causes a strong antioxidant effect by upregulating GPxs along with an increase in the cellular GSH level and upregulation of several isoforms of GSTs (not shown in the scheme), which reduces ROS [12] and blocks the NF-κB cascade early in the pathway. Besides, butyrate appears to inhibit the activation of the NF-κB cascade mainly by inhibiting the synthesis of its core components, which coincides with the inhibition of the activation of the NF-κB cascade. This results in the inhibition of NF-κB target gene expression, causing an anti-inflammatory response. Thus, there is a link between the antioxidant effect and anti-inflammatory response in butyrate-arrested VSMC proliferation, a crucial factor in atherogenesis.