Nerve growth factor protects oligodendrocytes from tumor necrosis factor-α-induced injury through Akt-mediated signaling mechanisms

Riya Takano, Shin Hisahara, Kazuhiko Namikawa, Hiroshi Kiyama, Hideyuki Okano, Masayuki Miurat

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Tumor necrosis factor-α is thought to be one of the most important inflammatory cytokines associated with the demyelinating disease multiple sclerosis. We determined whether neurotrophins could protect oligodendrocytes from tumor necrosis factor-α-mediated cytotoxicity. Among the neurotrophins tested, nerve growth factor was most effective at preventing cell death. Nerve growth factor also prevented the tumor necrosis factor-induced loss of mitochondrial membrane potential. Overexpression of constitutively active Akt, a downstream target of phosphatidylinositol 3-kinase, but not of constitutively active MEK, protected oligodendrocytes from tumor necrosis factor-induced injury. Moreover, overexpression of dominant-negative Akt negated the protective effects of nerve growth factor on tumor necrosis factor-mediated oligodendrocyte cytotoxicity. These findings indicate that the Akt pathway is crucial in nerve growth factor-mediated oligodendrocyte protection.

Original languageEnglish
Pages (from-to)16360-16365
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number21
DOIs
Publication statusPublished - 2000 May 26
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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