| Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. | |
| | |
MedLine Citation:
|
PMID: 9050895 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The interleukin 1beta converting enzyme (ICE) family plays a pivotal role in programmed cell death and has been implicated in stroke and neurodegenerative diseases. During reperfusion after filamentous middle cerebral artery occlusion, ICE-like cleavage products and tissue immunoreactive interleukin 1beta (IL-1beta) levels increased in ischemic mouse brain. Ischemic injury decreased after intracerebroventricular injections of ICE-like protease inhibitors, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.FMK), acetyl-Tyr-Val-Ala-Asp-chloromethylketone, or a relatively selective inhibitor of CPP32-like caspases, N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone, but not a cathepsin B inhibitor, N-benzyloxycarbonyl-Phe-Ala-fluoromethylketone. z-VAD.FMK decreased ICE-like cleavage products and tissue immunoreactive IL-1beta levels in ischemic mouse brain and reduced tissue damage when administered to rats as well. Only z-VAD.FMK and acetyl-Tyr-Val-Ala-Asp-chloromethylketone reduced brain swelling, and N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone did not attenuate the ischemia-induced increase in tissue IL-1beta levels. The three cysteine protease inhibitors significantly improved behavioral deficits, thereby showing that functional recovery of ischemic neuronal tissue can follow blockade of enzymes associated with apoptotic cell death. Finally, we examined the effect of z-VAD.FMK on excitotoxicity and found that it protected against alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-induced or to a lesser extent N-methyl-D-aspartate-induced excitotoxic brain damage. Thus, ICE-like and CPP32-like caspases contribute to mechanisms of cell death in ischemic and excitotoxic brain injury and provide therapeutic targets for stroke and neurodegenerative brain damage. |
| | |
Authors:
|
H Hara; R M Friedlander; V Gagliardini; C Ayata; K Fink; Z Huang; M Shimizu-Sasamata; J Yuan; M A Moskowitz |
Related Documents
:
|
17039455 - Induction of cell apoptosis in 3t3-l1 pre-adipocytes by flavonoids is associated with t... 12519385 - Nicotinamide is a potent inhibitor of proinflammatory cytokines. 10200555 - Emerging roles of caspase-3 in apoptosis. 18346055 - Arsenic trioxide-induced apoptosis in h9c2 cardiomyocytes: implications in cardiotoxicity. 20008175 - Bacteria associated with immunoregulatory cells in mice. 8195945 - Trypanosoma cruzi affects nitric oxide production by murine peritoneal macrophages. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 94 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1997 Mar |
Date Detail:
|
Created Date: 1997-04-07 Completed Date: 1997-04-07 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 2007-12 Citation Subset: IM |
Affiliation:
|
Department of Surgery and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Brain / drug effects, metabolism Brain Ischemia / drug therapy*, enzymology Caspase 1 Caspase 3 Caspases* Cathepsin B / antagonists & inhibitors Cerebrovascular Disorders / drug therapy Cysteine Endopeptidases / metabolism* Cysteine Proteinase Inhibitors / pharmacology* Gene Expression / genetics Interleukin-1 / metabolism Male Mice Neurons / drug effects*, metabolism Neurotoxins / pharmacology* Rats Rats, Sprague-Dawley Receptors, Glutamate / metabolism Reperfusion |
| Chemical | |
Reg. No./Substance:
|
0/Cysteine Proteinase Inhibitors; 0/Interleukin-1; 0/Neurotoxins; 0/Receptors, Glutamate; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.1/Cathepsin B; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Changes in multiple brain regions underlie species differences in a complex, congenital behavior.
Next Document: D-aspartate localizations imply neuronal and neuroendocrine roles.