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

被引:64
作者
Trapp, T [1 ]
Oláh, L [1 ]
Hölker, I [1 ]
Besselmann, M [1 ]
Tiesler, C [1 ]
Maeda, K [1 ]
Hossmann, KA [1 ]
机构
[1] Max Planck Inst Neurol Res, D-50931 Cologne, Germany
关键词
D O I
10.1006/mcne.2001.0971
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:883 / 894
页数:12
相关论文
共 33 条
[1]   Post-ischemic alterations in [3H]FK506 binding in the gerbil and rat brains [J].
Araki, T ;
Kato, H ;
Shuto, K ;
Itoyama, Y .
METABOLIC BRAIN DISEASE, 1998, 13 (01) :9-19
[2]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[3]  
Chen J, 1997, J NEUROCHEM, V69, P232
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]   PROTEIN-KINASE-C ACTIVATION INHIBITS GLUTAMATE-INDUCED CYTOTOXICITY IN A NEURONAL CELL-LINE [J].
DAVIS, JB ;
MAHER, P .
BRAIN RESEARCH, 1994, 652 (01) :169-173
[6]   Pathobiology of ischaemic stroke: an integrated view [J].
Dirnagl, U ;
Iadecola, C ;
Moskowitz, MA .
TRENDS IN NEUROSCIENCES, 1999, 22 (09) :391-397
[7]   Neuroprotective effects of gelsolin during murine stroke [J].
Endres, M ;
Fink, K ;
Zhu, JM ;
Stagliano, NE ;
Bondada, V ;
Geddes, JW ;
Azuma, T ;
Mattson, MP ;
Kwiatkowski, DJ ;
Moskowitz, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (03) :347-354
[8]   rhoB encoding a UV-inducible Ras-related small GTP-binding protein is regulated by GTPases of the Rho family and independent of JNK, ERK, and p38 MAP kinase [J].
Fritz, G ;
Kaina, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (49) :30637-30644
[9]   THE RAS-RELATED SMALL GTP-BINDING PROTEIN RHOB IS IMMEDIATE-EARLY INDUCIBLE BY DNA-DAMAGING TREATMENTS [J].
FRITZ, G ;
KAINA, B ;
AKTORIES, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (42) :25172-25177
[10]   Rho GTPases and the actin cytoskeleton [J].
Hall, A .
SCIENCE, 1998, 279 (5350) :509-514