title: Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and neuroblastoma cells.
abstract: Peroxisome proliferator-activated receptors (PPARs) play roles in neural cells by regulating energy balance, cell proliferation and anti-oxidant responses although the molecular mechanisms underlying such roles are unclear. Chronic exposure to excess manganese (Mn) leads to neurotoxicity, although Mn-induced neurotoxic mechanisms have not been fully elucidated. We hypothesized Mn neurotoxicity differentially alters the expression of PPARs. We investigated the effects of manganese chloride treatment (0.01-4 mM) on protein expression of PPAR isoforms (alpha, beta, and gamma) in human astrocytoma (U87) and neuroblastoma (SK-N-SH) cells. The two cell types expressed the 3 PPAR isoforms differentially: their expression of the PPARs was altered by Mn-treatment. Furthermore, nuclear and cytosolic fractions derived from the 2 cell types, with and without Mn-treatment, exhibited marked differences in the protein content of PPARs. Our results constitute the first demonstration that the PPAR signaling pathway may assume pathophysiological importance in Mn neurotoxicity.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Biomedical Research Institute, Idaho State University, 921 South 8th Avenue, Stop 8288, Pocatello, ID 83209-8288, USA.
authors.forename: Alfred Orina
authors.initials: AO
authors.lastname: Isaac
authors.forename: Ivana
authors.initials: I
authors.lastname: Kawikova
authors.forename: Alfred L M
authors.initials: AL
authors.lastname: Bothwell
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Daniels
authors.forename: James C K
authors.initials: JC
authors.lastname: Lai
mesh_terms: D001254:Astrocytoma / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D020149:Manganese Poisoning / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009687:Nuclear Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors