Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and neuroblastoma cells

Alfred Orina Isaac, Ivana Kawikova, Alfred L.M. Bothwell, Christopher K. Daniels, James C.K. Lai

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 (α, β, and γ) 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.

Original languageEnglish (US)
Pages (from-to)1305-1316
Number of pages12
JournalNeurochemical Research
Volume31
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

Keywords

  • Astrocytes
  • Astrocytoma and neuroblastoma cells
  • Manganese neurotoxicity
  • Neurons
  • Peroxisome proliferator-activated receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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