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The Anti-Aging and Tumor Suppressor Protein Klotho Enhances Differentiation of a Human Oligodendrocytic Hybrid Cell Line

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Abstract

Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats, and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here, we examined the signaling pathways induced by Klotho in MO3.13, a human oligodendrocytic hybrid cell line. We show that exogenous Klotho affects the ERK and Akt signaling pathways, decreases the proliferative abilities and enhances differentiation of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80 % of the differentially expressed genes being downregulated. Using gene set enrichment analysis, we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging, and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain and other malignancies.

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Abbreviations

PCR:

Polymerase chain reaction

DMEM:

Dulbecco’s modified Eagle’s Medium

PBS:

Phosphate buffered saline

FBS:

Fetal bovine serum

BSA:

Bovine serum albumin

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

MAG:

Myelin-associated glycoprotein

MBP:

Myelin basic protein

CNP:

2′,3′cyclic nucleotide-3′-phosphodiesterase

OPC:

Oligodendrocytic precursor cells

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Acknowledgments

We thank Drs. Yuriy Alekseyev and Marc Lenburg at Boston University Microarray Core Facility for help with the microarray analysis. We thank Chun-Tsin Hsu for assistance with the qRT-PCR experiment and Dr. Christina Khodr for helpful discussions. This work was supported by NIH-NIA grant AG-00001 to CRA, and an Ellison Foundation Award to CC.

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Authors and Affiliations

  1. Department of Biochemistry, Boston University School of Medicine, 72 E. Concord Street, K304, Boston, MA, 02118, USA

    Ci-Di Chen, Kathryn Hixson, Ella Zeldich & Carmela R. Abraham

  2. Department Biomedical Engineering, Boston University School of Medicine, Boston, MA, USA

    Hu Li

  3. Department of Biology, Boston University School of Medicine, Boston, MA, USA

    Jennifer Liang

  4. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Carmela R. Abraham

  5. Center for Individualized Medicine, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA

    Hu Li

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  1. Ci-Di Chen
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  2. Hu Li
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  3. Jennifer Liang
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  4. Kathryn Hixson
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  5. Ella Zeldich
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  6. Carmela R. Abraham
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Correspondence to Hu Li.

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Chen, CD., Li, H., Liang, J. et al. The Anti-Aging and Tumor Suppressor Protein Klotho Enhances Differentiation of a Human Oligodendrocytic Hybrid Cell Line. J Mol Neurosci 55, 76–90 (2015). https://doi.org/10.1007/s12031-014-0336-1

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  • DOI: https://doi.org/10.1007/s12031-014-0336-1

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