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Arsenic trioxide induces the apoptosis in vascular smooth muscle cells via increasing intracellular calcium and ROS formation

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Abstract

The present study was designed to investigate whether arsenic trioxide induced the apoptosis in rat mesenteric arterial smooth muscle cells (SMCs), which provides new insights into mechanisms of arsenic-related vascular diseases. Here, we found that arsenic trioxide significantly decreased the viability of SMCs in a dose-dependent manner. In addition, higher level of arsenic trioxide directly caused cellular necrosis. The Hoechst and AO/EB staining demonstrated that apoptotic morphological change was presented in SMCs exposed to arsenic trioxide. The TUNEL assay displayed that more positive apoptotic signal appeared in SMCs treated with arsenic trioxide. The following result showed that ROS formation was markedly increased in arsenic trioxide-treated SMCs. Pretreatment with N-acetylcysteine, an anti-oxidant reagent, obviously attenuated the enhancement of ROS production and the reduction of cell viability induced by arsenic trioxide in SMCs. Arsenic trioxide also enhanced free intracellular Ca2+ level in SMCs. BAPTA also significantly prevented the increased intracellular Ca2+ and decreased cell viability induced by arsenic trioxide in SMCs. These results suggested that arsenic trioxide obviously induced apoptosis in SMCs, and its mechanism was partially associated with intracellular ROS formation and free Ca2+ increasing.

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Acknowledgments

This work was supported by the National Basic Research program of China (973 programs: 2007CB512000/2007CB512007 to XQ Li), the Specialized Research Fund for the Doctoral Program of Higher Education (20060226019), and the Technologies R&D Program of Heilongjiang Province (GC06C33302).

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Authors and Affiliations

  1. Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Road 37#, 150001, Harbin, Heilongjiang, China

    Jing-Xiu Li, Xiaopeng Bai & Xue-Qi Li

  2. Department of Pharmacology, Harbin Medical University, 150081, Harbin, China

    Ya-Qi Shen, Ben-Zhi Cai, Jing Zhao & Yan-Jie Lu

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  1. Jing-Xiu Li
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  2. Ya-Qi Shen
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  3. Ben-Zhi Cai
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  4. Jing Zhao
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  5. Xiaopeng Bai
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  6. Yan-Jie Lu
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  7. Xue-Qi Li
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Correspondence to Xue-Qi Li.

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Li, JX., Shen, YQ., Cai, BZ. et al. Arsenic trioxide induces the apoptosis in vascular smooth muscle cells via increasing intracellular calcium and ROS formation. Mol Biol Rep 37, 1569–1576 (2010). https://doi.org/10.1007/s11033-009-9561-z

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  • DOI: https://doi.org/10.1007/s11033-009-9561-z

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