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https://hdl.handle.net/11499/5048
Title: | Inhibition of poly (ADP-ribose) polymerase and caspase-3, but not caspase-1, prevents apoptosis and improves spatial memory of rats with twice-repeated cerebral ischemia | Authors: | Hatip-Al-Khatib, İzzettin. Iwasaki, K. Chung, E.-H. Egashira, N. Mishima, K. Fujiwara, M. |
Keywords: | Apoptosis Caspase-1 Caspase-3 PARP Repeated cerebral ischemia/reperfusion Spatial memory 3 aminobenzamide caspase 3 caspase 3 inhibitor interleukin 1beta converting enzyme interleukin 1beta converting enzyme inhibitor nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor animal experiment animal model animal tissue apoptosis article blood vessel occlusion brain ischemia controlled study drug effect enzyme inhibition hippocampus immunohistochemistry male maze test memory disorder nonhuman rat spatial memory Animals Benzamides Brain Ischemia Caspase 1 Caspase 3 Caspases Dose-Response Relationship, Drug In Situ Nick-End Labeling Male Memory Disorders Oligopeptides Poly(ADP-ribose) Polymerases Rats Rats, Wistar |
Abstract: | The effect of inhibition of PARP [(poly (ADP-ribose) polymerase], caspase-3 and caspase-1 on twice-repeated ischemia-induced apoptosis and memory impairment were examined. The twicerepeated ischemia was induced by four-vessel occlusion method in which a 10 min ischemic episode was repeated once after 60 min. The spatial memory was assessed using 8-arm radial maze. The results of this study showed that the repeated ischemia impaired memory and induced apoptosis in hippocampus CA1 field after 7 days. Moreover, 3-aminobezamide (10 mg/kg i.v.), a PARP inhibitor, and Ac-DEVD-CHO (8.4 µg/5 µL i.c.v., bilaterally), a caspase-3 inhibitor, decreased apoptosis by 45% and 58% respectively. Both drugs reduced the error choices, but 3-aminobezamide additionally increased the correct choices and improved the memory when either drug was injected immediately after the ischemic insult. The results also showed that inhibition of interleukin-1ß-converting enzyme, ICE (caspase-1) by Z-ASP-DCB-CH2 (100 µg/kg i.c.v., bilaterally) neither decreased apoptosis (13% reduction) nor improved memory of the ischemic rats. These results suggest that direct inhibition of PARP and caspase-3, but not of caspase-1, prevents apoptosis and improves spatial memory impaired by repeated ischemia. © 2004 Published by Elsevier Inc. | URI: | https://hdl.handle.net/11499/5048 https://doi.org/10.1016/j.lfs.2004.05.014 |
ISSN: | 0024-3205 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection Tıp Fakültesi Koleksiyonu WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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