Sulfur dioxide induces apoptosis via reactive oxygen species generation in rat cardiomyocytes
Sulfur dioxide induces apoptosis via reactive oxygen species generation in rat cardiomyocytes
复制标题
二氧化硫通过大鼠心肌细胞中活性氧的产生诱导细胞凋亡。
DOI：
10.1007/s11356-019-04319-7
复制
发表时间：
2019-03-01
影响因子：
5.8
通讯作者：
Sang, Nan
中科院分区：
文献类型：
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作者：
Li, Shuyue;Xu, Zhifang;Sang, Nan
流行病学证据表明，心血管疾病的发病率和死亡率与二氧化硫（SO2）密切相关。在本研究中，H9 C2细胞与100 μ M NaHSO 3孵育，有或没有预处理的抗氧化剂，N-乙酰-L-半胱氨酸（NAC）。检测细胞凋亡率、线粒体膜电位（MMP）、ATP含量、caspase-3活性和活性氧（ROS）的变化。大鼠吸入7 mg/m3 SO2和/或腹腔注射50 mg/kg NAC，连续30 d。采用RT-PCR和Western blot方法分别检测各组大鼠结肠癌相关基因的mRNA和蛋白水平。NaHSO 3可诱导H9 C2细胞凋亡，降低MMP和ATP含量，诱导caspase-3表达。NAC可抑制NaHSO 3诱导的细胞凋亡。SO2和NaHSO 3可降低Bcl-2的表达和Bcl-2/Bax的比值，增加Bax和P53的积累和磷酸化，激活caspase-9和caspase-3。而NAC可减轻心肌缺血相关蛋白的变化。我们的研究结果表明，SO2诱导ROS介导的P53和caspase依赖的线粒体信号通路在H9 C2细胞和大鼠心脏。抗氧化治疗可以减轻SO2的不良反应，降低SO2引起的心血管疾病。
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 mu M 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/m(3) 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.