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

Fingerprint

Oligodendroglia
Nerve Growth Factor
Tumor Necrosis Factor-alpha
Wounds and Injuries
Nerve Growth Factors
Cytotoxicity
Phosphatidylinositol 3-Kinase
Mitochondrial Membrane Potential
Mitogen-Activated Protein Kinase Kinases
Demyelinating Diseases
Cell death
Multiple Sclerosis
Cell Death
Cytokines
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nerve growth factor protects oligodendrocytes from tumor necrosis factor-α-induced injury through Akt-mediated signaling mechanisms. / Takano, Riya; Hisahara, Shin; Namikawa, Kazuhiko; Kiyama, Hiroshi; Okano, Hideyuki; Miurat, Masayuki.

In: Journal of Biological Chemistry, Vol. 275, No. 21, 26.05.2000, p. 16360-16365.

Research output: Contribution to journalArticle

Takano, Riya ; Hisahara, Shin ; Namikawa, Kazuhiko ; Kiyama, Hiroshi ; Okano, Hideyuki ; Miurat, Masayuki. / Nerve growth factor protects oligodendrocytes from tumor necrosis factor-α-induced injury through Akt-mediated signaling mechanisms. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 21. pp. 16360-16365.
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