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Signaling Pathways Mediating Manganese-Induced Toxicity in Human Glioblastoma Cells (U87)

Neurochemical Research volume 31, pages 1211–1218 (2006)Cite this article

Abstract

Although essential, manganese (Mn) intake in excess leads to neurotoxicity. Mn neurotoxicity induces impairment of energy metabolism and ultimately cell death. Nevertheless, the signaling mechanisms underlying Mn toxicity are unknown. Employing human glioblastoma (U87) cells, we investigated several signaling pathways (ones promoting cellular proliferation and invasion) underlying Mn toxicity. Mn-treatment of U87 cells induced a down-regulation of MAPK pathway but the AKT pathway was not markedly affected. Mn-treatment of these cells induced decreases in their levels of c-Jun and c-Fos transcription factors and extracellular matrix degrading enzymes like MMP-2, which are associated with glioblastoma invasiveness. Mn-treatment also induced apoptosis in U87 cells. Thus, our results indicate that other than inducing apoptosis in U87 cells, Mn exerts differential effects on several signaling pathways promoting glioblastoma proliferation and invasion. Consequently, Mn may have pathophysiological roles in inducing apoptosis and in blocking glioblastoma invasion. Our results may thus have therapeutic implications.

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Acknowledgments

Our work was supported in part, by grants from Faculty Research Committee grant # 937, and University Research Committee grant # FY2002-09 at Idaho State University. K.L.E. was supported by an UgRC grant.

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Affiliations

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

    Shilpa Puli, James C. K. Lai, Kristina L. Edgley, Christopher K. Daniels & Alok Bhushan

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  1. Shilpa Puli
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  2. James C. K. Lai
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  3. Kristina L. Edgley
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  4. Christopher K. Daniels
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  5. Alok Bhushan
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Correspondence to Alok Bhushan.

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Puli, S., Lai, J.C.K., Edgley, K.L. et al. Signaling Pathways Mediating Manganese-Induced Toxicity in Human Glioblastoma Cells (U87). Neurochem Res 31, 1211–1218 (2006). https://doi.org/10.1007/s11064-006-9178-8

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  • DOI: https://doi.org/10.1007/s11064-006-9178-8

Keywords

  • Manganese
  • Manganese toxicity
  • Glioblastoma
  • Signaling
  • Cell death