Journal of Molecular Neuroscience

, Volume 55, Issue 1, pp 76–90

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

  • Ci-Di Chen
  • Hu Li
  • Jennifer Liang
  • Kathryn Hixson
  • Ella Zeldich
  • Carmela R. Abraham
Article

DOI: 10.1007/s12031-014-0336-1

Cite this article as:
Chen, CD., Li, H., Liang, J. et al. J Mol Neurosci (2015) 55: 76. doi:10.1007/s12031-014-0336-1

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.

Keywords

Aging Cancer Myelin Signaling pathways ERK Apoptosis Glia 

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

Supplementary material

12031_2014_336_MOESM1_ESM.doc (23 kb)
ESM 1(DOC 23 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ci-Di Chen
    • 1
  • Hu Li
    • 2
    • 5
  • Jennifer Liang
    • 3
  • Kathryn Hixson
    • 1
  • Ella Zeldich
    • 1
  • Carmela R. Abraham
    • 1
    • 4
  1. 1.Department of BiochemistryBoston University School of MedicineBostonUSA
  2. 2.Department Biomedical EngineeringBoston University School of MedicineBostonUSA
  3. 3.Department of BiologyBoston University School of MedicineBostonUSA
  4. 4.Department of Pharmacology and Experimental TherapeuticsBoston University School of MedicineBostonUSA
  5. 5.Center for Individualized Medicine, Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterUSA

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