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The Effects of Copper on Brain Microvascular Endothelial Cells and Claudin Via Apoptosis and Oxidative Stress

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Abstract

Many neurodegenerative diseases are related to copper although the effects on brain microvascular endothelial cells (BMECs) are poorly understood. In the present study, a primary BMEC culture model was established to evaluate the effects of copper on brain microvascular endothelial cells and whether claudin-1, claudin-3, claudin-5, and claudin-12 isoforms contribute to apoptosis and intrinsic antioxidant activity. Our results showed that copper ions had dual effects on BMECs by regulating intracellular reactive oxygen species (ROS) levels. Copper levels between 30 and 120 μM could enhance viability and promote proliferation. On the other hand, copper cytotoxicity was a result of apoptosis indicating a redox-independent manner of cell death. Expression levels of claudins were also regulated by copper in a concentration-dependent manner. We identified four claudin isoforms (1, 3, 5, and 12) and showed that their expression levels were regulated as a group by copper. Antioxidant activity of BMECs was also copper regulated, and superoxide dismutase and catalase were the main contributors to BMEC antioxidant functions. Together, our results indicated that copper had dual effects on BMEC growth and intrinsic antioxidant activities played a crucial role in BMEC survival and tight junction.

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Acknowledgments

This work was financially supported by National Natural Science Foundation of China (Nos. 31572585, 30871900, 30671550).

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Authors and Affiliations

  1. College of Veterinary Medicine, South China Agriculture University, WuShan Road 483, Guangzhou, 510642, China

    Jian Wang, Junquan Chen, Zhaoxin Tang, Ying Li, Lianmei Hu & Jiaqiang Pan

  2. Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, Guangzhou, 510642, China

    Jian Wang, Junquan Chen, Zhaoxin Tang, Ying Li, Lianmei Hu & Jiaqiang Pan

  3. Key Laboratory of Biotechnology and Bioproducts Development for Animal Epidemic Prevention, Ministry of Agriculture, Zhaoqing, 526238, China

    Zhaoxin Tang

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  1. Jian Wang
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Correspondence to Zhaoxin Tang.

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Experimental procedures involving animals were performed with the approval of the Laboratory Animal Management and Use Committee and Ethics Committee of South China Agricultural University.

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Wang, J., Chen, J., Tang, Z. et al. The Effects of Copper on Brain Microvascular Endothelial Cells and Claudin Via Apoptosis and Oxidative Stress. Biol Trace Elem Res 174, 132–141 (2016). https://doi.org/10.1007/s12011-016-0685-4

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