title: Oxygen free radicals regulate energy metabolism via AMPK pathway following cerebral ischemia.
abstract: OBJECTIVE
  One basic consequence of cerebral ischemia is energy depletion, manifested by falling levels of adenosine triphosphate (ATP) and a concomitant rise of adenosine monophosphate (AMP). Energy sensor AMP activated protein kinase (AMPK) can be activated in situations of energy stress to maintain ATP reserves. Here, we investigated the mechanism underlying AMPK pathway following cerebral ischemia in rat hippocampus.
  
  
  METHODS
  Male Sprague-Dawley rats (250 g or so) were subjected to 10 minute four-vessel occlusion, and ketamine or alpha-tocopherol was administered to the rats before ischemia, respectively. The plasma membrane and post-plasma membrane fractions were separated by centrifugation, and protein activity was assessed using immunoblot analysis.
  
  
  RESULTS
  AMPK was activated and reached its highest level at 1 hour reperfusion post-ischemia. Glucose transporter 4 (GLUT4), a downstream protein of AMPK, was increased in the plasma membrane while decreased in post-plasma membrane during reperfusion. Both N-methyl-D-aspartic acid (NMDA) receptor antagonist (ketamine) and oxygen free radical scavenger (alpha-tocopherol) decreased AMPK activity as well as the content of GLUT4 in the plasma membrane following cerebral ischemia.
  
  
  CONCLUSIONS
  Up-regulation of NMDA receptor activity or oxygen free radical production elicited by cerebral ischemia contributes to AMPK activation and increment of glucose uptake through facilitating the transportation of GLUT4 to the plasma membrane, involving in regulation of energy metabolism.
authors: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors: Meng
authors: M
authors: Li
authors: Jie
authors: J
authors: Zhao
authors: Yun
authors: Y
authors: Hu
authors: Hongbiao
authors: H
authors: Lu
authors: Jun
authors: J
authors: Guo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007649:Ketamine / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D024502:alpha-Tocopherol / Q000378:metabolism / Q000494:pharmacology
chemical_list: D051275:Glucose Transporter Type 4; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; D007649:Ketamine; D055372:AMP-Activated Protein Kinases; D024502:alpha-Tocopherol