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Role of HO-1 in the Arsenite-Induced Neurotoxicity in Primary Cultured Cortical Neurons

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Abstract

In the present study, the role of heme oxygenase (HO)-1 in sodium arsenite (arsenite)-induced neurotoxicity was investigated using primary cultured cortical neurons. Incubation with arsenite was found to cause cell death of primary cultured cortical neurons in concentration- and time-dependent manners. Furthermore, arsenite induced caspase 3 activation and decreased procaspase 12 levels, indicating that apoptosis is involved in the arsenite-induced neurotoxicity. The oxidative mechanism underlying arsenite-induced neurotoxicity was investigated. Western blot assay showed that arsenite significantly increased HO-1 levels, a redox-regulated protein. Co-incubation with glutathione (10 mM) attenuated arsenite-induced HO-1 elevation and caspase 3 activation, suggesting that oxidative stress is involved in the arsenite-induced neurotoxicity. The neurotoxic effects of inorganic arsenics were compared; arsenite was more potent than arsenate in inducing HO-1 expression and caspase 3 activation. Moreover, the cell viabilities of arsenite and arsenate were 60 ± 2 and 99 ± 2 % of control, respectively. HO-1 siRNA transfection was employed to prevent arsenite-induced HO-1 elevation. At the same time, arsenite-induced caspase 3 activation and neuronal death were attenuated in the HO-1 siRNA-transfected cells. Taken together, HO-1 appears to be neuroprotective in the arsenite-induced neurotoxicity in primary cultured cortical neurons. In addition to antioxidants, HO-1 elevation may be a neuroprotective strategy for arsenite-induced neurotoxicity.

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Acknowledgments

The authors express their gratitude to Dr. C.Y. Chai at Institute of Biomedical Sciences, Academia Sinica and Dr. L.S. Kao, Dean of School of Life Sciences, National Yang-Ming University, for their encouragement and support. This study was supported by NSC101-2320-B-010-044, VGHTPE-V102C-011, and a grant from the Ministry of Education, Aim for the Top University Plan, Taipei, Taiwan, R.O.C.

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Authors and Affiliations

  1. Institute of Physiology, National Yang-Ming University, Taipei, Taiwan

    Y. C. Teng, Y. I. Tai & Y. H. Lee

  2. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

    A. M. Y. Lin

  3. Institue of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    A. M. Y. Lin

  4. Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    A. M. Y. Lin

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  1. Y. C. Teng
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Correspondence to A. M. Y. Lin.

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Y.C. Teng and Y.I. Tai shared equal contribution.

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Teng, Y.C., Tai, Y.I., Lee, Y.H. et al. Role of HO-1 in the Arsenite-Induced Neurotoxicity in Primary Cultured Cortical Neurons. Mol Neurobiol 48, 281–287 (2013). https://doi.org/10.1007/s12035-013-8492-9

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  • DOI: https://doi.org/10.1007/s12035-013-8492-9

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