Differential activation of caspase-3 at two maturational stages during okadaic acid-induced rat neuronal death.
Okadaic acid (OA), a protein phosphatase inhibitor, is used as a research model of Alzheimer's disease to induce tau phosphorylation and neuronal death. We reported previously that OA induces neuronal apoptosis of immature neurons (in vitro days (IVD) 3-5), which is inhibited by cycloheximide (CHX). In this study, we demonstrate that CHX fails to prevent OA-induced neuronal death in mature neurons (IVD 14-15). Upon comparison of both types of dying cells, the immature neurons displayed characteristic features of apoptosis, such as nuclear fragmentation, phosphatidylserine externalization and prominent caspase-3 activation, while the mature neurons showed few characteristic features of apoptosis. Lack of the beneficial effects of CHX and the lesser activation of caspase-3 in the mature neurons argue against typical apoptotic neuronal death in the OA-induced neurodegeneration model.
Hong
Hea-Nam
HN
Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, South Korea.
Yoon
Seung-Yong
SY
Suh
Juyoun
J
Lee
Jong-Hwan
JH
Kim
DongHou
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D019319:Okadaic Acid / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D019319:Okadaic Acid; D003513:Cycloheximide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases