Modulation of copper-induced antioxidant defense, Cu transport, and mitophagy by hypoxia in the large yellow croaker (Larimichthys crocea)


This study aimed to investigate the effects of hypoxia on Cu-induced antioxidant defense, Cu transport, and mitophagy in the liver of the large yellow croaker. Fish were exposed to hypoxia (3.0 mg L−1), Cu (120 μg L−1), and hypoxia (3.0 mg L−1) plus Cu (120 μg L−1) for 48 h. Hypoxia exposure increased antioxidant abilities to maintain cellular redox balance. Although Cu exposure alone improved antioxidant defense, Cu transport, and mitophagy, these stress responses could not completely neutralize Cu toxicity, as reflected by the elevated reactive oxygen species (ROS) and lipid peroxidation (LPO) and hepatic vacuoles. When compared with Cu stress alone, hypoxia increased Cu toxicity by inhibiting antioxidant defense, Cu transport, and mitophagy, leading to the increment of mortality, ROS, and LPO, and the deterioration of histological structure. The adverse effects of hypoxia on Cu-induced metal transport and mitophagy might be involved in metal-responsive element-binding transcription factor-1 (MTF-1) and Forkhead box O-3 (FoxO3) signaling pathways, respectively. Overall, hypoxia reduced antioxidant response, Cu transport, and mitophagy in fish exposed to Cu, which contributes to understanding the molecular mechanisms underlying negative effects of hypoxia on Cu toxicity in fish.

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The authors thank the Yuyang Fisheries Co. Ltd. for providing the fish.

Funding information

This work was financially supported by the Fundamental Research Funds for Zhejiang Provincial Universities and Research Institutes (2019 J00039); the Natural Science Foundation of Zhejiang Province (Grant Nos. LY18D060008, LQ19E090007); and the Marine Special Project of the Zhoushan Technology Division (2017C41001).

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Correspondence to Lin Zeng.

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Pan, Y., Ai, C., Zeng, L. et al. Modulation of copper-induced antioxidant defense, Cu transport, and mitophagy by hypoxia in the large yellow croaker (Larimichthys crocea). Fish Physiol Biochem (2020) doi:10.1007/s10695-020-00765-0

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  • Hypoxia exposure
  • Cu toxicity
  • MTF-1
  • FoxO3
  • Larimichthys crocea