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Article: Deletion of aldose reductase leads to protection against cerebral ischemic injury

TitleDeletion of aldose reductase leads to protection against cerebral ischemic injury
Authors
KeywordsFree radical
Infarct
Knockout mice
MCAO
Polyol pathway
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jcbfm
Citation
Journal Of Cerebral Blood Flow And Metabolism, 2007, v. 27 n. 8, p. 1496-1509 How to Cite?
AbstractPreviously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR -/- brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR -/- brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury. © 2007 ISCBFM All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/67866
ISSN
2015 Impact Factor: 4.929
2015 SCImago Journal Rankings: 3.004
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLo, ACYen_HK
dc.contributor.authorCheung, AKHen_HK
dc.contributor.authorHung, VKLen_HK
dc.contributor.authorYeung, CMen_HK
dc.contributor.authorHe, QYen_HK
dc.contributor.authorChiu, JFen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2010-09-06T05:58:59Z-
dc.date.available2010-09-06T05:58:59Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Cerebral Blood Flow And Metabolism, 2007, v. 27 n. 8, p. 1496-1509en_HK
dc.identifier.issn0271-678Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/67866-
dc.description.abstractPreviously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR -/- brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR -/- brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury. © 2007 ISCBFM All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/jcbfmen_HK
dc.relation.ispartofJournal of Cerebral Blood Flow and Metabolismen_HK
dc.subjectFree radicalen_HK
dc.subjectInfarcten_HK
dc.subjectKnockout miceen_HK
dc.subjectMCAOen_HK
dc.subjectPolyol pathwayen_HK
dc.subject.meshAldehyde Reductase - antagonists & inhibitors - genetics - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshBehavior, Animal - physiologyen_HK
dc.subject.meshBrain - blood supply - cytology - metabolism - pathologyen_HK
dc.subject.meshBrain Injuries - metabolism - pathology - prevention & controlen_HK
dc.subject.meshBrain Ischemia - metabolism - pathology - prevention & controlen_HK
dc.subject.meshCaspase 3 - metabolismen_HK
dc.subject.meshGene Deletionen_HK
dc.subject.meshImidazolidines - metabolismen_HK
dc.subject.meshInfarction, Middle Cerebral Arteryen_HK
dc.subject.meshIron - metabolismen_HK
dc.subject.meshL-Iditol 2-Dehydrogenase - genetics - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Inbred CBAen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshOxidative Stressen_HK
dc.subject.meshReceptors, Transferrin - metabolismen_HK
dc.subject.meshTransferrin - metabolismen_HK
dc.subject.meshTyrosine - analogs & derivatives - metabolismen_HK
dc.titleDeletion of aldose reductase leads to protection against cerebral ischemic injuryen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0271-678X&volume=27&spage=1496&epage=1509&date=2007&atitle=Deletion+of+aldose+reductase+leads+to+protection+against+cerebral+ischemic+injury.en_HK
dc.identifier.emailLo, ACY: amylo@hkucc.hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.authorityLo, ACY=rp00425en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.jcbfm.9600452en_HK
dc.identifier.pmid17293845-
dc.identifier.scopuseid_2-s2.0-34250335011en_HK
dc.identifier.hkuros139979en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34250335011&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume27en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1496en_HK
dc.identifier.epage1509en_HK
dc.identifier.isiWOS:000248266700007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLo, ACY=7102780640en_HK
dc.identifier.scopusauthoridCheung, AKH=7401806412en_HK
dc.identifier.scopusauthoridHung, VKL=55112576200en_HK
dc.identifier.scopusauthoridYeung, CM=7201354151en_HK
dc.identifier.scopusauthoridHe, QY=34770287900en_HK
dc.identifier.scopusauthoridChiu, JF=7201501692en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK

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