Trolox and 6,7-dinitroquinoxaline-2,3-dione prevent necrosis but not apoptosis in cultured neurons subjected to oxygen deprivation.
There is a growing body of evidence suggesting that apoptosis is involved in ischemic brain injury. Recent studies suggest that a rapid necrosis masked a more subtle apoptotic death in neurons subjected to oxygen deprivation in culture. To test this hypothesis, we treated cultured neurons with potential antinecrotic drugs during and after oxygen deprivation. The results show that 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-hydroxy-2,5,7, 8-tetramethylchroman-2-carboxylic acid (Trolox), which interfered with kainate receptor activation and lipid peroxidation respectively, prevented necrosis but allowed neurons to undergo apoptosis. Flow cytometric analysis of DNA degradation and hydrogen peroxide generation, as well as fluorescent microscopy of nuclear fragmentation revealed that apoptotic activity was higher in 6, 7-dinitroquinoxaline-2,3-dione-treated cells than in Trolox-treated cells. This difference in occurrence of apoptosis may be due to the difference in oxidative stress generated from these two different agents.
Copin
J C
JC
CNS Injury and Edema Research Center, Department of Neurological Surgery, University of California, San Francisco, CA 94143-0651, USA.
Li
Y
Y
Reola
L
L
Chan
P H
PH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005434:Flow Cytometry; D002534:Hypoxia, Brain / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology*
D000975:Antioxidants; D002839:Chromans; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C056723:FG 9041; D004247:DNA; D010751:Phosphopyruvate Hydratase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid