Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Japan.
Biol Pharm Bull. 2011;34(9):1443-7. doi: 10.1248/bpb.34.1443.
Cadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactive oxygen species (ROS) and induces cytotoxicity. Extracellular-superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the cells from damaging effects of ROS; however, the effect of Cd on the expression of EC-SOD in COS7 cells remains unclear. In this study, exposure to cadmium chloride (CdCl₂) enhanced intracellular ROS generation and induced COS7 cell death. Moreover, exposure to Cd decreased the expression of EC-SOD at mRNA and protein levels, but not of other SOD isozymes, copper-and zinc-containing SOD and manganese-containing SOD. The reduction of EC-SOD and cell viability was partially attenuated by pretreatment with an antioxidant, N-acetylcysteine. Further, we determined the involvement of p38-mitogen-activated protein kinase (p38-MAPK) in the reduction of EC-SOD. From these observations, p38-MAPK signaling cascades activated by ROS play a pivotal role in the reduction of EC-SOD, and it is concluded that the reduction of EC-SOD leads to a decrease in the resistance to oxidative stress of Cd-exposed COS7 cells.
镉（Cd）是一种工业和环境污染物，优先积聚在肾脏中，这是与 Cd 相关毒性的主要靶标。据报道，Cd 暴露会产生活性氧（ROS）并诱导细胞毒性。细胞外超氧化物歧化酶（EC-SOD）是一种抗氧化酶，可保护细胞免受 ROS 的损伤作用；然而，Cd 对 COS7 细胞中 EC-SOD 表达的影响尚不清楚。在本研究中，氯化镉（CdCl₂）暴露会增强细胞内 ROS 的产生并诱导 COS7 细胞死亡。此外，Cd 暴露会降低 EC-SOD 在 mRNA 和蛋白质水平上的表达，但不会降低其他 SOD 同工酶、含铜和锌的 SOD 和含锰的 SOD 的表达。抗氧化剂 N-乙酰半胱氨酸预处理可部分减轻 EC-SOD 和细胞活力的降低。此外，我们确定了 p38-有丝分裂原激活的蛋白激酶（p38-MAPK）在 EC-SOD 降低中的参与。从这些观察结果中，可以得出结论，ROS 激活的 p38-MAPK 信号级联在 EC-SOD 的降低中起关键作用，并且认为 EC-SOD 的降低导致暴露于 Cd 的 COS7 细胞对氧化应激的抵抗力降低。
