STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes

Jan Xu, Shawei Chen, Hong Chen, Qingli Xiao, Chung Y. Hsu, Drew Michael, Jianxin Bao

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Methylprednisolone (MP), a synthetic glucocorticoid agonist, is widely used for the clinical therapy of white matter diseases in the nervous system, such as spinal cord injury and multiple sclerosis. In addition to its potent anti-inflammatory and antioxidant properties, we recently discovered a selective antiapoptotic effect of MP on oligodendrocytes via the activation of the glucocorticoid receptor (GR) and the upregulation of bcl-X L, asplicing isoform of the bcl-x gene. Based on published findings of the functional interactions between GR and STAT5, a transcription factor from the family of signal transducers and activators of transcription (STAT), we examined whether the glucocorticoid signaling pathway interacts with STAT5 to upregulate bcl-X L and protect oligodendrocytes. We showherein that (1) the GR and STAT5 complex is present on the STAT5-binding site of the bcl-x promoter region in oligodendrocytes; (2) the overexpression of an activated form of STAT5 prevents a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced oligodendrocyte cell death; and (3) this prevention is lost when the STAT5 gene is knocked down. Thus, our results provide one molecular mechanism underlying the postinjury protective effects of oligodendrocytes by stress hormones.

Original languageEnglish
Pages (from-to)2022-2026
Number of pages5
JournalJournal of Neuroscience
Volume29
Issue number7
DOIs
Publication statusPublished - Feb 18 2009

Fingerprint

Oligodendroglia
Methylprednisolone
Glucocorticoid Receptors
Glucocorticoids
Up-Regulation
STAT5 Transcription Factor
Leukoencephalopathies
Transducers
Spinal Cord Injuries
Genetic Promoter Regions
Nervous System
Genes
Multiple Sclerosis
Protein Isoforms
Cell Death
Anti-Inflammatory Agents
Antioxidants
Binding Sites
Hormones
Acids

Keywords

  • Glucocorticoid receptor
  • Methylprednisolone
  • Oligodendrocyte
  • Spinal cord injury
  • STAT5
  • Stress hormone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Xu, J., Chen, S., Chen, H., Xiao, Q., Hsu, C. Y., Michael, D., & Bao, J. (2009). STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes. Journal of Neuroscience, 29(7), 2022-2026. https://doi.org/10.1523/JNEUROSCI.2621-08.2009

STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes. / Xu, Jan; Chen, Shawei; Chen, Hong; Xiao, Qingli; Hsu, Chung Y.; Michael, Drew; Bao, Jianxin.

In: Journal of Neuroscience, Vol. 29, No. 7, 18.02.2009, p. 2022-2026.

Research output: Contribution to journalArticle

Xu, J, Chen, S, Chen, H, Xiao, Q, Hsu, CY, Michael, D & Bao, J 2009, 'STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes', Journal of Neuroscience, vol. 29, no. 7, pp. 2022-2026. https://doi.org/10.1523/JNEUROSCI.2621-08.2009
Xu, Jan ; Chen, Shawei ; Chen, Hong ; Xiao, Qingli ; Hsu, Chung Y. ; Michael, Drew ; Bao, Jianxin. / STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 7. pp. 2022-2026.
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