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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / drug effects
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Actin Cytoskeleton / enzymology
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Actin Cytoskeleton / pathology
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Animals
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Apoptosis / genetics
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Apoptosis / physiology*
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Brain Infarction / enzymology*
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Brain Infarction / genetics
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Brain Infarction / physiopathology
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Brain Ischemia / enzymology*
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Brain Ischemia / genetics
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Brain Ischemia / physiopathology
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Caspase 3
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Caspases / drug effects
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Caspases / metabolism
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Cells, Cultured / enzymology
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Cells, Cultured / pathology
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Cytochalasin D / pharmacology
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DNA Damage / genetics
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DNA, Single-Stranded / genetics
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Disease Models, Animal
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Gene Expression / physiology
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Hippocampus / enzymology
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Hippocampus / pathology
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Hippocampus / physiopathology
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Immunohistochemistry
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Mice
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Mice, Inbred C57BL
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Nerve Degeneration / enzymology*
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Nerve Degeneration / genetics
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Nerve Degeneration / physiopathology
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Neurons / enzymology
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Neurons / pathology
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Oligonucleotide Array Sequence Analysis
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Predictive Value of Tests
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Reperfusion Injury / enzymology*
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Reperfusion Injury / genetics
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Reperfusion Injury / physiopathology
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Time Factors
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Up-Regulation / genetics*
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rhoB GTP-Binding Protein / genetics
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rhoB GTP-Binding Protein / metabolism*
Substances
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DNA, Single-Stranded
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RNA, Messenger
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Cytochalasin D
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Casp3 protein, mouse
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Caspase 3
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Caspases
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rhoB GTP-Binding Protein