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Article: Transgenic mice overexpressing aldose reductase in Schwann cells show more severe nerve conduction velocity deficit and oxidative stress under hyperglycemic stress

TitleTransgenic mice overexpressing aldose reductase in Schwann cells show more severe nerve conduction velocity deficit and oxidative stress under hyperglycemic stress
Authors
Issue Date2003
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ymcne
Citation
Molecular And Cellular Neuroscience, 2003, v. 23 n. 4, p. 638-647 How to Cite?
AbstractTo further understand the role of aldose reductase (AR) in the etiology of diabetic neuropathy, we generated transgenic mice that overexpress AR specifically in the Schwann cells under the control of the rat myelin protein zero (P 0) promoter. One of the transgenic mouse lines, which has overexpression of AR mRNA in the Schwann cell only and higher AR activity in the sciatic nerve, was used to examine the relationship between increased AR activity and motor nerve conduction velocity (MNCV) deficit under diabetic and galactosemic conditions. Under these conditions, nontransgenic mice showed a slight reduction in MNCV compared to those of controls. However, transgenic mice exhibited a significantly greater reduction in MNCV under these conditions, particularly under galactosemic condition, indicating that a Schwann cell-specific increase in aldose reductase activity is sufficient to produce the phenotype. Interestingly, under galactosemic condition where the difference in MNCV deficit between transgenic and nontransgenic mice was most pronounced, there was no significant difference in accumulated galactitol levels in the sciatic nerve between these mice. These results indicate that increase in AR activity leads to greater reduction of MNCV under galactosemic and diabetic conditions, but galactitol and sorbitol levels may not be good indicators of the severity of neuropathy. On the other hand, the level of reduced glutathione (GSH) in the sciatic nerve was found to be correlated with the severity of MNCV deficit under the diabetic condition. Diabetic AR transgenic mice showed significant reduction of GSH in their sciatic nerve, whereas the diabetic nontransgenic mice showed no reduction in GSH level compared to the nondiabetic control, suggesting that AR is a key contributor to oxidative stress under diabetic condition. © 2003 Elsevier Science (USA). All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/88448
ISSN
2015 Impact Factor: 3.597
2015 SCImago Journal Rankings: 2.342
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSong, Zen_HK
dc.contributor.authorFu, DTWen_HK
dc.contributor.authorChan, YSen_HK
dc.contributor.authorLeung, Sen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2010-09-06T09:43:30Z-
dc.date.available2010-09-06T09:43:30Z-
dc.date.issued2003en_HK
dc.identifier.citationMolecular And Cellular Neuroscience, 2003, v. 23 n. 4, p. 638-647en_HK
dc.identifier.issn1044-7431en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88448-
dc.description.abstractTo further understand the role of aldose reductase (AR) in the etiology of diabetic neuropathy, we generated transgenic mice that overexpress AR specifically in the Schwann cells under the control of the rat myelin protein zero (P 0) promoter. One of the transgenic mouse lines, which has overexpression of AR mRNA in the Schwann cell only and higher AR activity in the sciatic nerve, was used to examine the relationship between increased AR activity and motor nerve conduction velocity (MNCV) deficit under diabetic and galactosemic conditions. Under these conditions, nontransgenic mice showed a slight reduction in MNCV compared to those of controls. However, transgenic mice exhibited a significantly greater reduction in MNCV under these conditions, particularly under galactosemic condition, indicating that a Schwann cell-specific increase in aldose reductase activity is sufficient to produce the phenotype. Interestingly, under galactosemic condition where the difference in MNCV deficit between transgenic and nontransgenic mice was most pronounced, there was no significant difference in accumulated galactitol levels in the sciatic nerve between these mice. These results indicate that increase in AR activity leads to greater reduction of MNCV under galactosemic and diabetic conditions, but galactitol and sorbitol levels may not be good indicators of the severity of neuropathy. On the other hand, the level of reduced glutathione (GSH) in the sciatic nerve was found to be correlated with the severity of MNCV deficit under the diabetic condition. Diabetic AR transgenic mice showed significant reduction of GSH in their sciatic nerve, whereas the diabetic nontransgenic mice showed no reduction in GSH level compared to the nondiabetic control, suggesting that AR is a key contributor to oxidative stress under diabetic condition. © 2003 Elsevier Science (USA). All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ymcneen_HK
dc.relation.ispartofMolecular and Cellular Neuroscienceen_HK
dc.subject.meshAldehyde Reductase - genetics - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAxons - enzymology - pathologyen_HK
dc.subject.meshDiabetic Neuropathies - enzymology - genetics - physiopathologyen_HK
dc.subject.meshDisease Models, Animalen_HK
dc.subject.meshDown-Regulation - geneticsen_HK
dc.subject.meshGalactitol - metabolismen_HK
dc.subject.meshGalactosemias - enzymology - genetics - physiopathologyen_HK
dc.subject.meshGlutathione - metabolismen_HK
dc.subject.meshHyperglycemia - enzymology - genetics - physiopathologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshNerve Fibers, Myelinated - enzymology - pathologyen_HK
dc.subject.meshNeural Conduction - geneticsen_HK
dc.subject.meshOxidative Stress - geneticsen_HK
dc.subject.meshSchwann Cells - cytology - enzymologyen_HK
dc.subject.meshStress, Physiological - enzymology - genetics - physiopathologyen_HK
dc.subject.meshUp-Regulation - geneticsen_HK
dc.titleTransgenic mice overexpressing aldose reductase in Schwann cells show more severe nerve conduction velocity deficit and oxidative stress under hyperglycemic stressen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1044-7431&volume=23&spage=638&epage=647&date=2003&atitle=Transgenic+mice+overexpressing+aldose+reductase+in+Schwann+cells+show+more+severe+nerve+conduction+velocity+deficit+and+oxidative+stress+under+hyperglycemic+stressen_HK
dc.identifier.emailChan, YS: yschan@hku.hken_HK
dc.identifier.emailLeung, S: suetyi@hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.authorityChan, YS=rp00318en_HK
dc.identifier.authorityLeung, S=rp00359en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S1044-7431(03)00096-4en_HK
dc.identifier.pmid12932443-
dc.identifier.scopuseid_2-s2.0-0042160232en_HK
dc.identifier.hkuros82139en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0042160232&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue4en_HK
dc.identifier.spage638en_HK
dc.identifier.epage647en_HK
dc.identifier.isiWOS:000185050400010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSong, Z=55455634500en_HK
dc.identifier.scopusauthoridFu, DTW=8138720700en_HK
dc.identifier.scopusauthoridChan, YS=7403676627en_HK
dc.identifier.scopusauthoridLeung, S=7202044886en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK

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