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

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.

• Authors: T Trapp, L Oláh, I Hölker, M Besselmann, C Tiesler, K Maeda, K A Hossmann
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 17 Issue 5 Pg. 883-94 (May 2001) ISSN: 1044-7431 [Print] United States
• PMID: 11358485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Academic Press.

Chemical References

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

Topics

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