Potential hazards of fenvalerate in massive pollution influence the apoptosis sensitivity
Potential hazards of fenvalerate in massive pollution influence the apoptosis sensitivity
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DOI：
10.1002/jat.3517
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发表时间：
2018-02
影响因子：
3.3
通讯作者：
Zheng-Guo Cui;Yu-Jie Jin;Lu Sun;S. A. Zakki;Mengling Li;Qian-Wen Feng;T. Kondo;R. Ogawa;H. Inadera
中科院分区：
文献类型：
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作者：
Zheng-Guo Cui;Yu-Jie Jin;Lu Sun;S. A. Zakki;Mengling Li;Qian-Wen Feng;T. Kondo;R. Ogawa;H. Inadera
氰戊菊酯（Fen）是一种合成拟除虫菊酯类杀虫剂，广泛应用于农业、家庭和兽医。Fen诱导异常的细胞增殖和凋亡，这与其危险作用有关。然而，这一观点是有争议的，潜在的分子机制仍然难以捉摸。在本研究中，Fen对镉（Cd）诱导的人髓性白血病U937细胞凋亡的影响及其相关的分子机制进行了研究。U937细胞用50 μm氯化镉（CdCl_2）处理，并在1-50 μm浓度下加入或不加入Fen预处理。细胞凋亡通过磷脂酰丝氨酸在质膜上的外化来评价。通过蛋白质印迹分析确定凋亡相关蛋白（包括Bcl-2家族成员）的表达水平。结果显示，20 μm的Fen预处理12 h可显著抑制Cd诱导的细胞凋亡。Fen和CdCl 2联合治疗后，观察到促凋亡Bcl-2家族蛋白（Noxa和Bid）的表达减少，抗凋亡蛋白（Bcl-xL，Mcl-1和XIAP）的表达增加。与CdCl 2单独处理相比，联合处理可增加ERK和AKT的磷酸化，而降低JNK的磷酸化。Fen可降低镉诱导的U937细胞凋亡敏感性。这种作用与ERK和AKT的激活、JNK的抑制以及Bcl-2家族蛋白和XIAP表达的变化有关。目前的研究结果表明，通过抑制细胞凋亡的镉毒性的潜在影响，芬。Fen可降低镉诱导的细胞凋亡敏感性，因此可能具有致癌风险，并对癌症治疗产生影响。
Fenvalerate (Fen), a synthetic pyrethroid insecticide, is widely used in agricultural, domestic and veterinary applications. Fen induces abnormal cell proliferation and apoptosis, which are linked to its hazardous effects. However, this view is controversial and the underlying molecular mechanisms remain elusive. In the present study, the effects of Fen on cadmium (Cd)‐induced apoptosis and the associated molecular mechanisms were investigated in human myeloid leukemia U937 cells. U937 cells were treated with 50 μm cadmium chloride (CdCl2) with or without Fen pretreatment at 1–50 μm. Apoptosis was evaluated by externalization of phosphatidylserine on the plasma membrane. The expression levels of apoptosis‐related proteins, including Bcl‐2 family members were determined by western blot analysis. The results revealed that pretreatment with Fen at 20 μm for 12 hours significantly inhibited Cd‐induced apoptosis. Decreased expression of pro‐apoptotic Bcl‐2 family proteins (Noxa and Bid) and increased expression of anti‐apoptotic proteins (Bcl‐xL, Mcl‐1 and XIAP) were observed after combined treatment with Fen and CdCl2. Phosphorylation of ERK and AKT was increased, while phosphorylation of JNK was decreased by the combined treatment, compared with CdCl2 treatment alone. In conclusion, Fen decreased apoptotic sensitivity induced by Cd in U937 cells. This effect was associated with activation of ERK and AKT, suppression of JNK and changes in expression of Bcl‐2 family proteins and XIAP. The present findings suggest a potential influence of Fen on Cd toxicity via suppression of apoptosis. Fen decreased apoptotic sensitivity induced by Cd, and thus it may contribute carcinogenic risk and influence on cancer therapy.