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Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma Cells

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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.

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Abbreviations

BCA:

Bicinchoninic acid

BSA:

Bovine serum albumin

DMEM:

Minimum essential medium eagle

GABA:

γ-aminobutyric acid

HEPES:

N-2 hydroxyethylpiperazine-N′-2-ethane sulfonic acid

HIF:

Hypoxia-inducible factor

Mn:

Manganese

PPARs:

Peroxisome proliferator-activated receptors

PVDF:

Polyvinylidene fluoride

RXRs:

Retinoid X receptors

SDS:

Sodium dodecyl sulfate

SK-N-SH:

A human neuroblastoma cell line

U87:

A human astrocytoma cell line

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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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Biomedical Research Institute, Idaho State University, 921 South 8th Avenue, Stop 8288, Pocatello, ID, 83209-8288, USA

    Alfred Orina Isaac, Christopher K. Daniels & James C. K. Lai

  2. Section of Immunobiology, Yale University School of Medicine, New Haven, CT, 06920, USA

    Ivana Kawikova & Alfred L. M. Bothwell

  3. Mountain States Tumor and Medical Research Institute, Boise, ID, 83712, USA

    James C. K. Lai

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  1. Alfred Orina Isaac
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  2. Ivana Kawikova
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  3. Alfred L. M. Bothwell
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  4. Christopher K. Daniels
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  5. James C. K. Lai
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Correspondence to James C. K. Lai.

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Isaac, A.O., Kawikova, I., Bothwell, A.L.M. et al. Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma Cells. Neurochem Res 31, 1305–1316 (2006). https://doi.org/10.1007/s11064-006-9173-0

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