Caspase-3-like protease activity-independent apoptosis at the onset of neuronal cell death in the gerbil hippocampus after global ischemia.
To investigate the relationship between caspase-3-like protease activity, which has been suggested to be related to apoptosis, and DNA fragmentation, we measured changes in caspase-3-like activity and DNA fragmentation in the hippocampus of gerbils exposed to global ischemia induced by bilateral occlusion of the carotid arteries for 5 min. Caspase-3-like protease activity began to increase at day 4 post-ischemia, reached a peak at day 5, and declined thereafter. The levels of DNA fragmentation, evaluated in terms of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) staining and cytosolic nucleosomes, in the ischemic hippocampus began to increase significantly at day 3 after ischemia, reached a peak at day 4, and decreased thereafter. Our data suggest that DNA fragmentation in ischemic hippocampus of gerbils precedes caspase-3-like protease activation. Our results indicate that a caspase-3-like protease-independent apoptotic pathway operates, at least at the onset of neuronal cell death, in the hippocampus of gerbils after global ischemia.
Shimizu
Hiroki
H
Clinical Research Center, Eisai Co., Ltd., Tokyo, Japan. h3-shimizu@hhc.eisai.co.jp
Ohgoh
Makoto
M
Ikeda
Masuhiro
M
Nishizawa
Yukio
Y
Ogura
Hiroo
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism
D009707:Nucleosomes; D053148:Caspase 3