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Manganese-Induced Neurotoxicity is Differentially Enhanced by Glutathione Depletion in Astrocytoma and Neuroblastoma Cells

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Abstract

Manganese (Mn) is neurotoxic: the underlying mechanisms have not been fully elucidated. l-Buthionine-(S,R)-sulfoximine (BSO) is an irreversible inhibitor of γ-glutamylcysteine synthetase, an important enzyme in glutathione (GSH) synthesis. To test the hypothesis that BSO modulates Mn toxicity, we investigated the effects of treatment of U-87 or SK-N-SH cells with MnCl2, BSO, or MnCl2 plus BSO. We monitored cell viability using MTT assay, staining with HO-33342 to assess live and/or apoptotic cells, and staining with propidium iodide (PI) to assess necrotic cells; we also measured cellular glutathione. Our results indicate decreased viability in both cell types when treated with MnCl2 or BSO: Mn was more toxic to SK-N-SH cells, whereas BSO was more toxic to U-87 cells. Because BSO treatment accentuated Mn toxicity in both cell lines, GSH may act to combat Mn toxicity. Thus, further investigation in oxidative stress mediated by glutathione depletion will unravel new Mn toxicity mechanism(s).

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Acknowledgments

This study was supported by a grant from Idaho Biomedical Research Infrastructure Network (NIH NCRR BRINIP20RR016454) and an Idaho State University FRC grant. The authors thank Isaac Alfred Orina for his helpful suggestions. V.V. Dukhande thanks the Idaho INBRE NIH program (grant # P20RR016454) for a research fellowship.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Biomedical Research Institute, Idaho State University, Pocatello, ID, 83209-8288, USA

    Vikas V. Dukhande, Gauri H. Malthankar-Phatak, Jeremy J. Hugus, Christopher K. Daniels & James C. K. Lai

  2. Northwest Nazarene University, Nampa, ID, 83686-5897, USA

    Jeremy J. Hugus

  3. Mountain States Tumor and Medical Research Institute, Boise, ID, 83712, USA

    James C. K. Lai

Authors
  1. Vikas V. Dukhande
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  2. Gauri H. Malthankar-Phatak
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  3. Jeremy J. Hugus
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  4. Christopher K. Daniels
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  5. James C. K. Lai
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Correspondence to James C. K. Lai.

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Dukhande, V.V., Malthankar-Phatak, G.H., Hugus, J.J. et al. Manganese-Induced Neurotoxicity is Differentially Enhanced by Glutathione Depletion in Astrocytoma and Neuroblastoma Cells. Neurochem Res 31, 1349–1357 (2006). https://doi.org/10.1007/s11064-006-9179-7

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  • DOI: https://doi.org/10.1007/s11064-006-9179-7

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