Department of public health and preventive medicine, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China.
Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, Guangdong, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
Ecotoxicol Environ Saf. 2022 May 1;236:113494. doi: 10.1016/j.ecoenv.2022.113494. Epub 2022 Apr 9.
Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to explore the mechanism of mitochondrial respiratory chain dysfunction during apoptosis induced by cadmium chloride (CdCl). Cell viability was evaluated by cell proliferation assay and different concentrations of 60, 80 and 100 μM were selected to evaluate the mitochondrial toxicity of CdCl respectively. Under the CdCl treatment for 24 h, the mitochondrial reactive oxygen species (ROS) of HK-2 cells increased and the superoxide dismutase (SOD) activity was inhibited at the above three concentrations separately. Both ATP content and mitochondrial membrane potential decreased significantly at 100 μM concentration. The levels of procaspase-3 and Bcl-2 had fallen in a concentration-dependent manner and Bax was significantly increased at 60, 80 and 100 μM concentration compared with no CdCl treatment respectively, which activated the mitochondrial apoptosis pathway. N-acetyl-cysteine (NAC) could partially resist CdCl-induced cell apoptosis, while myxothiazol (Myx) promoted the process. Mitochondria relative alterations manifested as inhibition of complex III and V. In addition, both the quantity of mitochondrial coenzyme Q-binding protein CoQ10 homolog B (CoQ10B) and cytochrome c (Cyt c) had decreased significantly. Taken together, CdCl induced HK-2 apoptosis due to the mitochondrial respiratory chain dysfunction by reducing the CoQ10B level, offering a novel evaluating indicator for the environmental toxicity of CdCl.
镉可诱导细胞凋亡，可能与线粒体呼吸链功能障碍有关。用人近端肾小管（HK-2）细胞探索氯化镉（CdCl）诱导凋亡过程中线粒体呼吸链功能障碍的机制。用细胞增殖实验评估细胞活力，选择不同浓度的 60、80 和 100 μM 分别评估 CdCl 的线粒体毒性。在 CdCl 处理 24 h 后，HK-2 细胞的线粒体活性氧（ROS）增加，三种浓度的超氧化物歧化酶（SOD）活性均受到抑制。100 μM 浓度时，ATP 含量和线粒体膜电位显著降低。60、80 和 100 μM 浓度时，前半胱氨酸天冬氨酸蛋白酶-3（procaspase-3）和 B 细胞淋巴瘤-2（Bcl-2）水平呈浓度依赖性下降，Bax 水平明显升高，与无 CdCl 处理组相比，激活了线粒体凋亡途径。N-乙酰半胱氨酸（NAC）可部分抵抗 CdCl 诱导的细胞凋亡，而米酵菌酸（Myx）促进了这一过程。线粒体相对变化表现为抑制复合物 III 和 V。此外，线粒体辅酶 Q 结合蛋白 CoQ10 同源物 B（CoQ10B）和细胞色素 c（Cyt c）的数量均显著减少。综上所述，CdCl 通过降低 CoQ10B 水平诱导 HK-2 细胞凋亡，为 CdCl 的环境毒性提供了一种新的评价指标。
