GTPase RhoB: an early predictor of neuronal death after transient focal ischemia in mice.
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.
Trapp
T
T
Max Planck Institute for Neurological Research, Gleueler Strasse 50, 50931 Cologne, Germany. trapp@mpin-koeln.mpg.de
Oláh
L
L
Hölker
I
I
Besselmann
M
M
Tiesler
C
C
Maeda
K
K
Hossmann
K A
KA
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020520:Brain Infarction / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000201:enzymology / Q000473:pathology; D015638:Cytochalasin D / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics*; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D004277:DNA, Single-Stranded; D012333:RNA, Messenger; D015638:Cytochalasin D; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020743:rhoB GTP-Binding Protein