TY - JOUR
T1 - Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and neuroblastoma cells
AU - Isaac, Alfred Orina
AU - Kawikova, Ivana
AU - Bothwell, Alfred L.M.
AU - Daniels, Christopher K.
AU - Lai, James C.K.
N1 - Funding Information:
Acknowledgments Our studies were supported by a grant from Idaho Biomedical Research Infrastructure Network (NIH NCRR BRINIP20RR016454), an Idaho State University Faculty Research Committee grant, and a small project grant from the Mountain States Tumor and Medical Research Institute.
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Astrocytoma and neuroblastoma cells
KW - Manganese neurotoxicity
KW - Neurons
KW - Peroxisome proliferator-activated receptors
UR - http://www.scopus.com/inward/record.url?scp=33751276214&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751276214&partnerID=8YFLogxK
U2 - 10.1007/s11064-006-9173-0
DO - 10.1007/s11064-006-9173-0
M3 - Article
C2 - 17053972
AN - SCOPUS:33751276214
SN - 0364-3190
VL - 31
SP - 1305
EP - 1316
JO - Neurochemical Research
JF - Neurochemical Research
IS - 11
ER -