title: Signaling pathways mediating manganese-induced toxicity in human glioblastoma cells (u87).
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Biomedical Research Institute, Idaho State University, Pocatello, ID 83209, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Puli
authors.forename: James C K
authors.initials: JC
authors.lastname: Lai
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Edgley
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Daniels
authors.forename: Alok
authors.initials: A
authors.lastname: Bhushan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D020935:MAP Kinase Signaling System; D008345:Manganese / Q000633:toxicity*; D015398:Signal Transduction
chemical_list: D008345:Manganese