Oxidative stress and neuronal death/survival signaling in cerebral ischemia

被引:191
作者
Saito, A
Maier, CM
Narasimhan, P
Nishi, T
Song, YS
Yu, FS
Liu, L
Lee, YS
Nito, C
Kamada, H
Dodd, RL
Hsieh, LB
Hassid, B
Kim, EE
González, M
Chan, PH [1 ]
机构
[1] Stanford Univ, Sch Med, Dept Neurosurg, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Program Neurosci, Stanford, CA 94305 USA
关键词
cerebral ischemia; oxidative stress; superoxide dismutase; mitochondria; stroke; oxygen radicals; survival signaling; apoptosis; PI3-kinase; Akt;
D O I
10.1385/MN:31:1-3:105
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
It has been demonstrated by numerous studies that apoptotic cell death pathways are implicated in ischemic cerebral injury in ischemia models in vivo. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides oxygen as a substrate for numerous enzymatic oxidation reactions and for mitochondrial oxidative phosphorylation to produce adenosine triphosphate. Oxygen radicals, the products of these biochemical and physiological reactions, are known to damage cellular lipids, proteins, and nucleic acids and to initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways could provide novel therapeutic strategies in clinical stroke.
引用
收藏
页码:105 / 116
页数:12
相关论文
共 86 条
[61]  
Murakami K, 1998, J NEUROSCI, V18, P205
[62]   Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice [J].
Murakami, K ;
Kondo, T ;
Epstein, CJ ;
Chan, PH .
STROKE, 1997, 28 (09) :1797-1804
[63]  
Namura S, 1998, J NEUROSCI, V18, P3659
[64]   Copper-zinc superoxide dismutase affects Akt activation after transient focal cerebral ischemia in mice [J].
Noshita, N ;
Sugawara, T ;
Lewén, A ;
Hayashi, T ;
Chan, PH .
STROKE, 2003, 34 (06) :1513-1518
[65]  
Noshita N, 2002, J NEUROSCI, V22, P7923
[66]   Manganese superoxide dismutase affects cytochrome c release and caspase-9 activation after transient focal cerebral ischemia in mice [J].
Noshita, N ;
Sugawara, T ;
Fujimura, M ;
Morita-Fujimura, Y ;
Chan, PH .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (05) :557-567
[67]   Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia [J].
Pérez-Pinzón, MA ;
Xu, GP ;
Born, J ;
Lorenzo, J ;
Busto, R ;
Rosenthal, M ;
Sick, TJ .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1999, 19 (01) :39-43
[68]   PRO-INFLAMMATORY CYTOKINES AND ENVIRONMENTAL-STRESS CAUSE P38 MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION BY DUAL PHOSPHORYLATION ON TYROSINE AND THREONINE [J].
RAINGEAUD, J ;
GUPTA, S ;
ROGERS, JS ;
DICKENS, M ;
HAN, JH ;
ULEVITCH, RJ ;
DAVIS, RJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (13) :7420-7426
[69]   Neuroprotective role of a proline-rich akt substrate in apoptotic neuronal cell death after stroke: Relationships with nerve growth factor [J].
Saito, A ;
Narasimhan, P ;
Hayashi, T ;
Okuno, S ;
Ferrand-Drake, M ;
Chan, PH .
JOURNAL OF NEUROSCIENCE, 2004, 24 (07) :1584-1593
[70]  
Saito A, 2003, J NEUROSCI, V23, P1710