铜(Cu)和镉(Cd)在工业活动中被广泛使用,导致全球水生系统中的Cu和Cd污染。尽管Cu在许多生物学功能中起着至关重要的作用,过量的金属引起细胞毒性。相比之下,Cd是通常与Cu共存的非必要金属。一起,它们在细胞中引起氧化应激,导致细胞损伤。这些金属离子也被认为引起细胞凋亡。在这项研究中,我们用斑马鱼肝细胞系,ZFL,研究Cu和Cd联合细胞毒性。虽然Cd比Cu更有毒,两者都被发现调节氧化应激相关基因的表达,也没有显着改变氧化应激相关酶的活性。与抗氧化剂N-乙酰基-1-半胱氨酸和Cu螯合剂的共同暴露测试表明,Cd毒性是由于Cu引起的氧化应激所致,并且低浓度的Cu实际上可以对ZFL中的氧化应激发挥抗氧化作用。过量的Cu浓度触发了引发半胱天冬酶(半胱天冬酶8和半胱天冬酶9)的表达,但抑制了执行者半胱天冬酶(半胱天冬酶3)的表达,停止细胞凋亡。Cd只能触发起始半胱天冬酶的表达;它不能阻止细胞凋亡。然而,低浓度的铜降低了线粒体超氧化物水平,抑制Cd诱导的ZFL细胞凋亡效应。
Copper (Cu) and cadmium (Cd) are widely used in industrial activities, resulting in Cu and Cd contamination in aquatic systems worldwide. Although Cu plays an essential role in many biological functions, an excessive amount of the metal causes cytotoxicity. In contrast, Cd is a non-essential metal that usually co-exists with Cu. Together, they cause oxidative stress in cells, leading to cell damage. These metal ions are also believed to cause cell apoptosis. In this study, we used a zebrafish liver cell line, ZFL, to study combined Cu and Cd cytotoxicity. Although Cd is more toxic than Cu, both were found to regulate the expression of oxidative stress related genes, and neither significantly altered the activity of oxidative stress related enzymes. Co-exposure tests with the antioxidant N-acetyl-l-cysteine and the Cu chelator bathocuproinedisulfonic acid disodium salt demonstrated that Cd toxicity was due to the oxidative stress caused by Cu, and that Cu at a low concentration could in fact exert an antioxidant effect against the oxidative stress in ZFL. Excessive Cu concentration triggered the expression of initiator caspases (caspase 8 and caspase 9) but suppressed that of an executioner caspase (caspase 3), halting apoptosis. Cd could only trigger the expression of initiator caspases; it could not halt apoptosis. However, a low concentration of Cu reduced the mitochondrial superoxide level, suppressing the Cd-induced apoptotic effects in ZFL.