scholarly journals The Cytosolic Antioxidant Copper/Zinc-Superoxide Dismutase Prevents the Early Release of Mitochondrial Cytochrome c in Ischemic Brain after Transient Focal Cerebral Ischemia in Mice

2000 ◽  
Vol 20 (8) ◽  
pp. 2817-2824 ◽  
Author(s):  
Miki Fujimura ◽  
Yuiko Morita-Fujimura ◽  
Nobuo Noshita ◽  
Taku Sugawara ◽  
Makoto Kawase ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Focal Cerebral Ischemia ◽  
Mitochondrial Cytochrome ◽  
Ischemic Brain ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Transient Focal Cerebral Ischemia ◽  
Copper Zinc

Correlation between copper/zinc superoxide dismutase and the proliferation of neural stem cells in aging and following focal cerebral ischemia

2006 ◽  
Vol 104 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Sunao Takemura ◽  
Takamasa Kayama ◽  
Atsushi Kuge ◽  
Hasmat Ali ◽  
Yasuaki Kokubo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cerebral Ischemia ◽  
Transgenic Mice ◽  
Focal Cerebral Ischemia ◽  
Wild Type ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Transient Focal Cerebral Ischemia ◽  
Copper Zinc

Object Neural stem cells (NSCs) have been demonstrated in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus (DG). Although aging rats manifest a decrease in NSCs, rats exposed to stress (for example, ischemia, epilepsy, radiation, and trauma) show an increase in these cells. In transgenic mice, the overexpression of human copper/zinc superoxide dismutase (SOD1), an endogenous antioxidant, has been reported to be a protective enzyme against transient focal cerebral ischemia. The authors investigated the correlation between SOD1 and the proliferation of NSCs in aging as chronic oxidative stress (Experiment 1) and acute oxidative stress induced by transient focal cerebral ischemia (Experiment 2) in mice. Methods Bromodeoxyuridine (BrdU) was used in the evaluation of NSCs. In Experiment 1, NSCs in the SVZ significantly increased in 16-month-old transgenic mice compared with wild-type mice (p = 0.0001). In Experiment 2, mice were subjected to 30-minute occlusions of the middle cerebral artery. The increase in NSCs in the DG in transgenic mice was significantly greater than that in wild-type mice (p < 0.05). Conclusions Results in this study suggest that chronic and acute oxidative stress may inhibit the proliferation of NSCs and that SOD1 may play a key role in NSC proliferation.

scholarly journals Increased Expression of a Proline-Rich Akt Substrate (PRAS40) in Human Copper/Zinc-Superoxide Dismutase Transgenic Rats Protects Motor Neurons from Death after Spinal Cord Injury

2007 ◽  
Vol 28 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Fengshan Yu ◽  
Purnima Narasimhan ◽  
Atsushi Saito ◽  
Jing Liu ◽  
Pak H Chan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Superoxide Dismutase ◽  
Motor Neurons ◽  
Focal Cerebral Ischemia ◽  
Akt Inhibitor ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Cord Injury ◽  
Copper Zinc

The serine-threonine kinase, Akt, plays an important role in the cell survival signaling pathway. A proline-rich Akt substrate, PRAS40, has been characterized, and an increase in phospho-PRAS40 (pPRAS40) is neuroprotective after transient focal cerebral ischemia. However, the involvement of PRAS40 in the cell death/survival pathway after spinal cord injury (SCI) is unclear. Liposome-mediated PRAS40 transfection was performed to study whether overexpression of pPRAS40 is neuroprotective. We further examined the expression of pPRAS40 after SCI by immunohistochemistry and Western blot using copper/zinc-superoxide dismutase (SOD1) transgenic (Tg) rats and wild-type (Wt) littermates. We then examined the relationship between PRAS40 and Akt by injection of LY294002, a phosphatidylinositol 3-kinase (PI3K) pathway inhibitor, or Akt inhibitor IV, a compound that inhibits Akt activation after SCI. Our data demonstrated that increased pPRAS40 resulted in survival of more motor neurons compared with control complementary DNA transfection. Phosphorylated PRAS40 increased in the Wt rats after SCI, whereas there was a greater and prolonged increase in the SOD1 Tg rats. Coimmunoprecipitation showed that binding of pPRAS40 with 14-3-3 increased 1 day after SCI in the Wt rats, whereas there was a significant increase in the Tg rats. The inhibitor studies showed that phospho-Akt and pPRAS40 were decreased after injection of LY294002 or Akt inhibitor IV. We conclude that an increase in pPRAS40 by transfection after SCI results in survival of motor neurons, and overexpression of SOD1 in the Tg rats results in an increase in endogenous pPRAS40 and a decrease in motor neuron death through the PI3K/Akt pathway.

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