File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Aldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damage

TitleAldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damage
Authors
KeywordsAR, aldose reductase
ARI, AR inhibitor
DHE, dihydroethidium
ERK, extracellular signal-regulated kinase-1
JNK, c-Jun NH2 terminal kinase
MAPK, mitogen-activated protein kinase
MNCV, motor nerve conduction velocity
PAR, poly(ADP-ribose)
Issue Date2006
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2006, v. 55 n. 7, p. 1946-1953 How to Cite?
AbstractThe exaggerated flux through polyol pathway during diabetes is thought to be a major cause of lesions in the peripheral nerves. Here, we used aldose reductase (AR)-deficient (AR-/-) and AR inhibitor (ARI)-treated mice to further understand the in vivo role of polyol pathway in the pathogenesis of diabetic neuropathy. Under normal conditions, there were no obvious differences in the innervation patterns between wild-type AR (AR+/+) and AR -/- mice. Under short-term diabetic conditions, AR-/- mice were protected from the reduction of motor and sensory nerve conduction velocities observed in diabetic AR+/+ mice. Sorbitol levels in the sciatic nerves of diabetic AR+/+ mice were increased significantly, whereas sorbitol levels in the diabetic AR-/- mice were significantly lower than those in diabetic AR+/+ mice. In addition, signs of oxidative stress, such as increased activation of c-Jun NH2-terminal kinase (JNK), depletion of reduced glutathione, increase of superoxide formation, and DNA damage, observed in the sciatic nerves of diabetic AR+/+ mice were not observed in the diabetic AR-/- mice, indicating that the diabetic AR-/- mice were protected from oxidative stress in the sciatic nerve. The diabetic AR-/- mice also excreted less 8-hydroxy-2′-deoxyguanosine in urine than diabetic AR+/+ mice. The structural abnormalities observed in the sural nerve of diabetic AR +/+ mice were less severe in the diabetic AR-/- mice, although it was only mildly protected by AR deficiency under short-term diabetic conditions. Signs of oxidative stress and functional and structural abnormalities were also inhibited by the ARI fidarestat in diabetic AR +/+ nerves, similar to those in diabetic AR-/- mice. Taken together, increased polyol pathway flux through AR is a major contributing factor in the early signs of diabetic neuropathy, possibly through depletion of glutathione, increased superoxide accumulation, increased JNK activation, and DNA damage. © 2006 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/76945
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHo, ECMen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorYuk, SCen_HK
dc.contributor.authorYip, JCWen_HK
dc.contributor.authorArvindakshan, Men_HK
dc.contributor.authorYamagishi, SIen_HK
dc.contributor.authorYagihashi, Sen_HK
dc.contributor.authorOates, PJen_HK
dc.contributor.authorEllery, CAen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2010-09-06T07:26:36Z-
dc.date.available2010-09-06T07:26:36Z-
dc.date.issued2006en_HK
dc.identifier.citationDiabetes, 2006, v. 55 n. 7, p. 1946-1953en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76945-
dc.description.abstractThe exaggerated flux through polyol pathway during diabetes is thought to be a major cause of lesions in the peripheral nerves. Here, we used aldose reductase (AR)-deficient (AR-/-) and AR inhibitor (ARI)-treated mice to further understand the in vivo role of polyol pathway in the pathogenesis of diabetic neuropathy. Under normal conditions, there were no obvious differences in the innervation patterns between wild-type AR (AR+/+) and AR -/- mice. Under short-term diabetic conditions, AR-/- mice were protected from the reduction of motor and sensory nerve conduction velocities observed in diabetic AR+/+ mice. Sorbitol levels in the sciatic nerves of diabetic AR+/+ mice were increased significantly, whereas sorbitol levels in the diabetic AR-/- mice were significantly lower than those in diabetic AR+/+ mice. In addition, signs of oxidative stress, such as increased activation of c-Jun NH2-terminal kinase (JNK), depletion of reduced glutathione, increase of superoxide formation, and DNA damage, observed in the sciatic nerves of diabetic AR+/+ mice were not observed in the diabetic AR-/- mice, indicating that the diabetic AR-/- mice were protected from oxidative stress in the sciatic nerve. The diabetic AR-/- mice also excreted less 8-hydroxy-2′-deoxyguanosine in urine than diabetic AR+/+ mice. The structural abnormalities observed in the sural nerve of diabetic AR +/+ mice were less severe in the diabetic AR-/- mice, although it was only mildly protected by AR deficiency under short-term diabetic conditions. Signs of oxidative stress and functional and structural abnormalities were also inhibited by the ARI fidarestat in diabetic AR +/+ nerves, similar to those in diabetic AR-/- mice. Taken together, increased polyol pathway flux through AR is a major contributing factor in the early signs of diabetic neuropathy, possibly through depletion of glutathione, increased superoxide accumulation, increased JNK activation, and DNA damage. © 2006 by the American Diabetes Association.en_HK
dc.languageengen_HK
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.subjectAR, aldose reductaseen_HK
dc.subjectARI, AR inhibitoren_HK
dc.subjectDHE, dihydroethidiumen_HK
dc.subjectERK, extracellular signal-regulated kinase-1en_HK
dc.subjectJNK, c-Jun NH2 terminal kinaseen_HK
dc.subjectMAPK, mitogen-activated protein kinaseen_HK
dc.subjectMNCV, motor nerve conduction velocityen_HK
dc.subjectPAR, poly(ADP-ribose)en_HK
dc.subject.meshAldehyde Reductase - deficiency - geneticsen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshDNA Damageen_HK
dc.subject.meshDiabetes Mellitus, Experimental - genetics - physiopathologyen_HK
dc.subject.meshEnzyme Activationen_HK
dc.subject.meshFructose - metabolismen_HK
dc.subject.meshGenes, Reporteren_HK
dc.subject.meshGlucose - metabolismen_HK
dc.subject.meshGlutathione - metabolismen_HK
dc.subject.meshInositol - metabolismen_HK
dc.subject.meshJNK Mitogen-Activated Protein Kinases - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshMotor Neurons - physiologyen_HK
dc.subject.meshNeural Conduction - physiologyen_HK
dc.subject.meshPoly Adenosine Diphosphate Ribose - metabolismen_HK
dc.subject.meshReference Valuesen_HK
dc.subject.meshSorbitol - metabolismen_HK
dc.subject.meshSuperoxides - metabolismen_HK
dc.subject.meshSural Nerve - physiopathologyen_HK
dc.titleAldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damageen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1797&volume=55&issue=7&spage=1946&epage=53&date=2006&atitle=Aldose+reductase-deficient+mice+are+protected+from+delayed+motor+nerve+conduction+velocity,+increased+c-Jun+NH2-terminal+kinase+activation,+depletion+of+reduced+glutathione,+increased+superoxide+accumulation,+and+DNA+damageen_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.2337/db05-1497en_HK
dc.identifier.pmid16804062-
dc.identifier.scopuseid_2-s2.0-33747069158en_HK
dc.identifier.hkuros123647en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747069158&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume55en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1946en_HK
dc.identifier.epage1953en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000238764600006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHo, ECM=14028314400en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridYuk, SC=36922492300en_HK
dc.identifier.scopusauthoridYip, JCW=36839139700en_HK
dc.identifier.scopusauthoridArvindakshan, M=6507214472en_HK
dc.identifier.scopusauthoridYamagishi, SI=7102183565en_HK
dc.identifier.scopusauthoridYagihashi, S=7006805482en_HK
dc.identifier.scopusauthoridOates, PJ=7004883807en_HK
dc.identifier.scopusauthoridEllery, CA=6507792790en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats