Hypoxic neuronal necrosis: protein synthesis-independent activation of a cell death program.
Hypoxic necrosis of dentate gyrus neurons in primary culture required the activation of an orderly cell death program independent of protein synthesis. Early mitochondrial swelling and loss of the mitochondrial membrane potential were accompanied by release of cytochrome c and followed by caspase-9-dependent activation of caspase-3. Caspase-3 and -9 inhibitors reduced neuronal necrosis. Calcium directly induced cytochrome c release from isolated mitochondria. Hypoxic neuronal necrosis may be an active process in which the direct effect of hypoxia on mitochondria may lead to the final common pathway of caspase-3-mediated neuronal death.
Niquet
Jerome
J
Epilepsy Research, Research 151, Veterans Affairs Greater Los Angeles Healthcare System and Department of Neurology David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA. jniquet@ucla.edu
Baldwin
Roger A
RA
Allen
Suni G
SG
Fujikawa
Denson G
DG
Wasterlain
Claude G
CG
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia; D007150:Immunohistochemistry; D007477:Ions / Q000378:metabolism; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017830:Octoxynol / Q000494:pharmacology; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D013997:Time Factors
D061945:Caspase Inhibitors; D003902:Detergents; D004791:Enzyme Inhibitors; D007477:Ions; D011500:Protein Synthesis Inhibitors; D017830:Octoxynol; D003513:Cycloheximide; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D012966:Sodium Cyanide; D002118:Calcium