Figure 2.

Direct and indirect mechanism of SCFAs on Nrf2 activation for modulation of oxidative stress. Binding of SCFAs to GPRC receptors induces direct activation of the nuclear factor Nrf2. Butyrate, on the other hand, also has a synergistic effect on Nrf2 activation because it diffuses into the cell lumen and, through HDAC inhibition, increases the production of histone H3K9ac, thus inducing an epigenetic modification on the Nrf2 promoter, indirectly activating Nrf2-dependent gene translocation and transcription. Abbreviations: AMPK, Activated Protein Kinase; HDAC, Histone Deacetylase; Nrf2, Nuclear Erythroid-Related Factor 2; ARE, Antioxidant Response element; HO-1, Heme Oxygenase-1; NQO1, NAD(P)H Quinone Dehydrogenase-1; NF-κB, Nuclear Factor Kappa-light-chain-enhancer of Activated B cells; SOD1, Superoxide Dismutase 1; GST, Glutathione S-transferase.