Bcl-2-related protein family gene expression during oligodendroglial differentiation

Takayuki Ito, Aki Itoh, David E Pleasure

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Oligodendroglial lineage cells (OLC) vary in susceptibility to both necrosis and apoptosis depending on their developmental stages, which might be regulated by differential expression of Bcl-2-related genes. As an initial step to test this hypothesis, we examined the expression of 19 Bcl-2-related genes in purified cultures of rat oligodendroglial progenitors, immature and mature oligodendrocytes. All 'multidomain' anti-apoptotic members (Bcl-x, Bcl-2, Mcl-1, Bcl-w and Bcl2110/ Diva/Boo) except Bcl2a1/A1 are expressed in OLC. Semiquantitative and real-time RT-PCR revealed that Bcl-xL and Mcl-1 mRNAs are the dominant anti-apoptotic members and increase four- and twofold, respectively, with maturation. Bcl-2 mRNA is less abundant than Bcl-xL mRNA in progenitors and falls an additional 10-fold during differentiation. Bcl-w mRNA also increases, with significant changes in its splicing pattern, as OLC mature. Transfection studies demonstrated that Bcl-xL overexpression protects against kainate-induced excito- toxicity, whereas Bcl-2 overexpression does not. As for 'multidomain' pro-apoptotic members (Bax, Bad and Bok/ Mtd), Bax and Bak are highly expressed throughout differentiation. Among 'BH3 domain-only' members examined (Bim, Biklk, DP5/Hrk, Bad, Bid, Noxa, Puma/Bbc3, Bmf, BNip3 and BNip3L), BNip3 and Bmf mRNAs increase markedly during differentiation. These results provide basic information to guide further studies on the roles for Bcl-2-related family proteins in OLC death.

Original languageEnglish (US)
Pages (from-to)1500-1512
Number of pages13
JournalJournal of Neurochemistry
Volume85
Issue number6
DOIs
StatePublished - Jun 2003
Externally publishedYes

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Keywords

  • Apoptosis
  • Bcl-2-related protein family
  • Excito- toxicity
  • Oligodendroglial lineage
  • Real-time PCR
  • Transfection

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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