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Published on: May 24, 2024
Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and
Alfred Orina Isaac1, Ivana Kawikova, Alfred L M Bothwell
1Department of Pharmaceutical Sciences, College of Pharmacy, Biomedical Research Institute, Idaho State University, 921 South 8th Avenue, Stop 8288, Pocatello, ID 83209-8288, USA.
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.
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