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

Mol Cell Neurosci. 2001 May;17(5):883-94. doi: 10.1006/mcne.2001.0971.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / enzymology
  • Actin Cytoskeleton / pathology
  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Brain Infarction / enzymology*
  • Brain Infarction / genetics
  • Brain Infarction / physiopathology
  • Brain Ischemia / enzymology*
  • Brain Ischemia / genetics
  • Brain Ischemia / physiopathology
  • Caspase 3
  • Caspases / drug effects
  • Caspases / metabolism
  • Cells, Cultured / enzymology
  • Cells, Cultured / pathology
  • Cytochalasin D / pharmacology
  • DNA Damage / genetics
  • DNA, Single-Stranded / genetics
  • Disease Models, Animal
  • Gene Expression / physiology
  • Hippocampus / enzymology
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / enzymology*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology
  • Neurons / enzymology
  • Neurons / pathology
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / physiopathology
  • Time Factors
  • Up-Regulation / genetics*
  • rhoB GTP-Binding Protein / genetics
  • rhoB GTP-Binding Protein / metabolism*

Substances

  • DNA, Single-Stranded
  • RNA, Messenger
  • Cytochalasin D
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • rhoB GTP-Binding Protein