Zhang Xintang, Xu Fei, Hu Xiaoli, Meng Jie
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266000, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266000, China; University of the Chinese Academy of Sciences, China.
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266000, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, 266000, China; University of the Chinese Academy of Sciences, China.
Mar Environ Res. 2025 Oct;211:107393. doi: 10.1016/j.marenvres.2025.107393. Epub 2025 Jul 22.
To elucidate the interaction between zinc (Zn) and copper (Cu), this study investigates the mechanisms by which Zn mediates detoxification of Cu toxicity in the Pacific oyster Crassostrea gigas. Physiological indices and transcriptome analyses under control (CTR), Cu, and Zn_Cu treatments reveal that excess Cu induces systemic toxicity in oysters. Cu accumulation in tissues alters metal transporters, downregulating Cu importers and exporters (Zn and Cu transporters) while upregulating chaperones and metallothionein (MT1) for detoxification. Zn supplementation alleviates these effects by enhancing MT1 expression, blocking Cu uptake, and restoring metal homeostasis. Cu stress also increases reactive oxygen species (ROS) and disrupts antioxidant responses, with superoxide dismutase (SOD) overactivation and suppression of catalase1 (CAT1) and glutathione peroxidase (GPX2), leading to potential HO accumulation. Zn supplementation reduces oxidative stress by restoring CAT1 and GPX2 expression, promoting glutathione metabolism, thus maintaining redox balance. Furthermore, Cu suppresses immune signaling by downregulating TLR-MyD88-NF-κB pathway genes and promotes apoptosis through caspase3/7 activation and reduced anti-apoptotic gene expression. Zn partially reverses these effects by reactivating immune genes and reducing caspase levels, though Cu's immune suppression remains dominant. In conclusion, at the tested concentrations (100 μg/L Cu and 50 μg/L Zn) and Zn/Cu ratio, Zn supplementation mitigated Cu-induced oxidative stress and immune suppression in hemocytes, demonstrating its potential for mitigating Cu toxicity in aquaculture.
为阐明锌（Zn）与铜（Cu）之间的相互作用，本研究调查了Zn介导太平洋牡蛎（Crassostrea gigas）中Cu毒性解毒的机制。对照（CTR）、Cu处理和Zn_Cu处理下的生理指标和转录组分析表明，过量的Cu会诱导牡蛎产生全身毒性。组织中的Cu积累会改变金属转运蛋白，下调Cu的输入和输出蛋白（Zn和Cu转运蛋白），同时上调伴侣蛋白和金属硫蛋白（MT1）以进行解毒。补充Zn可通过增强MT1表达、阻止Cu摄取和恢复金属稳态来减轻这些影响。Cu胁迫还会增加活性氧（ROS）并破坏抗氧化反应，导致超氧化物歧化酶（SOD）过度激活以及过氧化氢酶1（CAT1）和谷胱甘肽过氧化物酶（GPX2）受到抑制，从而导致潜在的羟基自由基（HO）积累。补充Zn可通过恢复CAT1和GPX2表达、促进谷胱甘肽代谢来降低氧化应激，从而维持氧化还原平衡。此外，Cu通过下调TLR-MyD88-NF-κB信号通路基因来抑制免疫信号，并通过激活caspase3/7和降低抗凋亡基因表达来促进细胞凋亡。Zn通过重新激活免疫基因和降低caspase水平部分逆转了这些影响，不过Cu的免疫抑制作用仍然占主导地位。总之，在所测试的浓度（100μg/L Cu和50μg/L Zn）及Zn/Cu比例下，补充Zn减轻了Cu诱导的血细胞氧化应激和免疫抑制，证明了其在减轻水产养殖中Cu毒性方面的潜力。
