Sulfur dioxide induces apoptosis via reactive oxygen species generation in rat cardiomyocytes
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Epidemiological evidence suggests that the incidence and mortality of cardiovascular diseases are closely related to sulfur dioxide (SO2). In the present study, H9C2 cells were incubated with 100 μM NaHSO3 with or without pretreatment of an antioxidant, N-acetyl-l-cysteine (NAC). The changes of apoptosis rate, mitochondrial membrane potential (MMP), ATP content, caspase-3 activity, and reactive oxygen species (ROS) were detected. Rats were inhaled 7 mg/m3 SO2 and/or intraperitoneal injected with 50 mg/kg (bw) of NAC for 30 days. RT-PCR and Western blot were used to detect the mRNA and protein levels of apoptosis-related genes. We found that the apoptosis of H9C2 cells was induced by NaHSO3, which decreased the content of MMP and ATP, and induced the expression of caspase-3. NAC can inhibit the apoptosis induced by NaHSO3 treatment. SO2 and NaHSO3 decreased the expression of Bcl-2 and the ratio of Bcl-2/Bax, increased the expression of Bax and P53 accumulation and phosphorylation, and activated caspase-9 and caspase-3. Whereas NAC can reduce the changes of apoptosis-related proteins in rat heart. Our results suggest that SO2 induces ROS-mediated P53 and caspase-dependent mitochondrial signaling pathways in H9C2 cells and rat hearts. Antioxidant therapy can reduce the adverse reactions of SO2 and lead to a decline in the cardiovascular disease induced by SO2.
KeywordsSulfur dioxide Apoptosis Hearts Antioxidant Reactive oxygen species
This research was supported by the National Natural Science Foundation of China (21777091, 21377076, 91543203, 21222701), Research Project for Young Sanjin Scholarship of Shanxi, Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi, State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (KF2016-17), and Research Project Supported by Shanxi Scholarship Council of China (015-006).
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