GTPase RhoB: An early predictor of neuronal death after transient focal ischemia in mice

Thorsten Trapp, Laszlo Oláh, Irmgard Hölker, Michael Besselmann, Christine Tiesler, Keiichiro Maeda, Konstantin Alexander Hossmann

Research output: Article

63 Citations (Scopus)

Abstract

Applying the recently developed DNA array technique to a murine stroke model, we found that the gene coding for RhoB, a member of the family of GTPases that regulate a variety of signal transduction pathways, is upregulated in ischemia-damaged neurons. RhoB immunoreactivity precedes DNA single-strand breaks and heralds the evolving infarct, making it an early predictor of neuronal death. Expression of RhoB colocalized with drastic rearrangement of the actin cytoarchitecture indicates a role for Rho in postischemic morphological changes. Apoptosis in a murine hippocampal cell line was also associated with an early increase in RhoB protein. Activation of caspase-3, a crucial step in apoptosis, could be inhibited by cytochalasin D, a substance that counteracts the actin-modulating activity of Rho GTPases, indicating that Rho proteins may have impact on injury-initiated neuronal signal transduction. Our findings make Rho GTPases potential targets for the development of drugs aimed at limiting neuronal death following brain damage.

Original languageEnglish
Pages (from-to)883-894
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume17
Issue number5
DOIs
Publication statusPublished - jan. 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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