Fig 1: Erythrocyte Nrf2 and plasma Keap1 quantified by the transcription factor assay and western blot analysis, respectively. (a) Nrf2 was measured in erythrocytes, isolated from the whole blood of healthy volunteers, through a high-throughput assay that combines quick ELISA with a sensitive and specific nonradioactive one for transcription factor activation. By this kind of assay, only the activated Nrf2 is detected (Materials and Methods). (b) Plasma collected from healthy volunteers was considered to identify the presence of the Keap1 through western blot analysis that is shown as the densitometric unit of the bands (Materials and Methods). The data are shown as the mean value ± SD and are representative of three independent experiments (n = 3). P values were adjusted with the unpaired t-test: *P < 0.05, **P < 0.01, and ****P < 0.0001 between the indicated subgroups. GraphPad Prism 7 was used to create the figure.
Fig 2: Influence of ApoE e4 polymorphism and physical activity in the pathways of the proteasome system. The presence of ApoE e4 polymorphism was associated with an elevated concentration of the proteasome-related Keap1, which inhibited Nfr2 and impaired the proteasome system. These events lead to an enhancement of Aß and miR-153-3p, as well as to minor plasma AOC. Aside from ApoE polymorphism, regular physical exercise reduced oxidative stress, by increasing the plasma antioxidant capability, and blocked the pathway of Aß production/accumulation. Physical exercise can also regulate the epigenetic mechanisms involved in the Nrf2-Keap1 axis and Aß production by reducing miR-153-3p and HDAC6 and enhancing miR-195-5p expression.
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