Fig. 4
PEG-CNPs counteract oxidative stress via activating Nrf2/Keap1 signaling pathway. Relative mRNA expressions of DJ-1 a, Nrf2 b, and Keap1 c in HT-29 cells after different treatments. d Schematic diagram of the experimental protocol to evaluate the role of Nrf2 by small interfering RNA (SiRNA) in vitro using qRT-PCR analysis and flow cytometry. e Relative mRNA expressions of Nrf2 in SiNrf2-transfected HT-29 cells. f Flow cytometry analysis of apoptosis in SiNrf2-transfected HT-29 cells. g Apoptosis rate of HT-29 cells. h The anti-oxidative genes (Nqo1, Gpx1, HO-1) and i pro-oxidative genes (Nox-2, Cyp2e1) expression levels in HT-29 cells treated with PEG-CNPs and H2O2. Relative mRNA expressions of HO-1 j and Nox-2 k. l Schematic representation of the mechanism of PEG-CNPs in reducing ROS level. PEG-CNPs decompose DDP-induced H2O2 into H2O and O2. Meanwhile, the minimally residual ROS activate the Nrf2/Keap1 signaling pathway. Specifically, Nrf2 moves into the nucleus and subsequently binds to the antioxidant response elements (ARE), leading to the upregulation of the antioxidant gene (HO-1) and downregulation of the pro-oxidant gene (Nox-2). These gene regulations can further detoxify ROS. Data represent means ± s.d. n = 3. #P < 0.1, ##P < 0.01, ###P < 0.001 vs. control group; *P < 0.1, **P < 0.01, ***P < 0.001 vs. H2O2 group