Nicotine and Cotinine Inhibit Catalase and Glutathione Reductase Activity Contributing to the Impaired Osteogenesis of SCP-1 Cells Exposed to Cigarette Smoke

Figure 5

NAC and L-ascorbate enhance the osteogenic differentiation in SCP-1 cells exposed to CSE by activation of Nrf-2 signaling and through radical scavenging. Proposed mechanisms for oxidative stress impair osteogenic differentiation under CSE exposure and potential roles of antioxidant. High-level oxidative stress generated by CSE resulted in oxidative damage and impaired SCP-1 cells’ osteogenic differentiation. ROS induced through CSE exposure can oxidize the Cys residues on Keap-1, leading to the conformational change and releasing Nrf2. Phospho-Nrf2 can translocate to the nucleus and activates the antioxidant response element (ARE) leading to an activation of antioxidant genes. However, activation of Nrf2 in CSE exposure cells may not be enough to protect the cells from the oxidative stress generated by CSE. NAC activates upstream p38 MAPKinase, which is required to activate Nrf2 and transactivate antioxidant genes that may reduce oxidative stress induced by CSE. L-Asc might act with thiol residues of Keap-1, increasing the levels of Nrf2 available. CSE inhibited catalase activity being not able to process H₂O₂. GR activity is also affected by CSE to a decrease of total GSH. NAC and L-Asc treatment decreased CSE-induced ROS production by increasing the biosynthesis of GSH via Nrf2 signaling and also by radical scavenging. CSE decreased the enzymatic activity of SOD and catalase, leading to accumulation of ^⋅O₂⁻ and H₂O₂ in the cells. Additionally, CSE decreased total GSH and decreased GR activity causing that there is no GSH availed. Therefore, GPx cannot catalyze the reduction of H₂O₂ to H₂O. Nicotine and cotinine, despite not affecting the osteogenic differentiation of the cells, evidenced negative inhibitory effects on the enzymatic activity of catalase and GR. Nicotine and cotinine imbalance the antioxidative system contributing in part to the negative effects in the osteogenic differentiation of SCP-1 cell exposure to CSE.