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Article: Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress

TitleCardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress
Authors
KeywordsAldose reductase
Sarco(endo)plasmic reticulum Ca 2+-ATPase
Sorbitol dehydrogenase
Issue Date2010
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/
Citation
American Journal Of Physiology - Cell Physiology, 2010, v. 299 n. 3, p. C643-C653 How to Cite?
AbstractHyperglycemia is an indication of poor outcome for heart attack patients, even for nondiabetic patients with stress-induced hyperglycemia. Previous studies showed that inhibition of aldose reductase, the first and rate-limiting enzyme of the polyol pathway, attenuated contractile dysfunction in diabetic animals, but the mechanism is unclear. We therefore wanted to find out whether the polyol pathway also contributes to acute hyperglycemia-induced cardiac contractile dysfunction, and determine the mechanism involved. Rat hearts were isolated and retrogradely perfused with Krebs buffer containing either normal or high concentrations of glucose for 2 h. Short exposure to high-glucose medium led to contractile dysfunction as indicated by decreased -dP/dt max, as well as elevation in left ventricular end-diastolic pressure. Cardiomyocytes incubated in high-glucose medium showed abnormal Ca 2+ signaling, most likely because of decreased activity of sarco(endo)plasmic reticulum Ca 2+-ATPase (SERCA) inactivated by oxidative stress. Inhibition of aldose reductase or sorbitol dehydrogenase, the second enzyme in the polyol pathway, ameliorated contractile dysfunction, attenuated oxidative stress, and normalized Ca 2+ signaling and SERCA activity caused by high glucose, indicating that the polyol pathway is the major contributor to acute hyperglycemia-induced oxidative stress leading to the inactivation of SERCA and contractile dysfunction. Copyright © 2010 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/124488
ISSN
2015 Impact Factor: 3.395
2015 SCImago Journal Rankings: 1.893
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
The University of Hong Kong
National Institutes of HealthRO1-HL-31607-25
American Diabetes Association7-09-JF-69
Funding Information:

This work was supported by The University of Hong Kong Committee on Research and Conference Grants. X. Y. Tong and X. Y. Hou were supported by National Institutes of Health Grant RO1-HL-31607-25 and American Diabetes Association Grant 7-09-JF-69.

References

 

DC FieldValueLanguage
dc.contributor.authorTang, WHen_HK
dc.contributor.authorCheng, WTen_HK
dc.contributor.authorKravtsov, GMen_HK
dc.contributor.authorTong, XYen_HK
dc.contributor.authorHou, XYen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorChung, SSMen_HK
dc.date.accessioned2010-10-31T10:37:13Z-
dc.date.available2010-10-31T10:37:13Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Physiology - Cell Physiology, 2010, v. 299 n. 3, p. C643-C653en_HK
dc.identifier.issn0363-6143en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124488-
dc.description.abstractHyperglycemia is an indication of poor outcome for heart attack patients, even for nondiabetic patients with stress-induced hyperglycemia. Previous studies showed that inhibition of aldose reductase, the first and rate-limiting enzyme of the polyol pathway, attenuated contractile dysfunction in diabetic animals, but the mechanism is unclear. We therefore wanted to find out whether the polyol pathway also contributes to acute hyperglycemia-induced cardiac contractile dysfunction, and determine the mechanism involved. Rat hearts were isolated and retrogradely perfused with Krebs buffer containing either normal or high concentrations of glucose for 2 h. Short exposure to high-glucose medium led to contractile dysfunction as indicated by decreased -dP/dt max, as well as elevation in left ventricular end-diastolic pressure. Cardiomyocytes incubated in high-glucose medium showed abnormal Ca 2+ signaling, most likely because of decreased activity of sarco(endo)plasmic reticulum Ca 2+-ATPase (SERCA) inactivated by oxidative stress. Inhibition of aldose reductase or sorbitol dehydrogenase, the second enzyme in the polyol pathway, ameliorated contractile dysfunction, attenuated oxidative stress, and normalized Ca 2+ signaling and SERCA activity caused by high glucose, indicating that the polyol pathway is the major contributor to acute hyperglycemia-induced oxidative stress leading to the inactivation of SERCA and contractile dysfunction. Copyright © 2010 the American Physiological Society.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiologyen_HK
dc.subjectAldose reductaseen_HK
dc.subjectSarco(endo)plasmic reticulum Ca 2+-ATPaseen_HK
dc.subjectSorbitol dehydrogenaseen_HK
dc.subject.meshAcute Diseaseen_HK
dc.subject.meshAldehyde Reductase - physiologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCalcium Signalingen_HK
dc.subject.meshGlucose - pharmacologyen_HK
dc.subject.meshGlutathione - metabolismen_HK
dc.subject.meshHeart - physiopathologyen_HK
dc.subject.meshHyperglycemia - metabolism - physiopathologyen_HK
dc.subject.meshLactic Acid - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMyocardial Contractionen_HK
dc.subject.meshMyocardium - metabolismen_HK
dc.subject.meshOxidation-Reductionen_HK
dc.subject.meshOxidative Stressen_HK
dc.subject.meshPerfusionen_HK
dc.subject.meshPeroxynitrous Acid - metabolismen_HK
dc.subject.meshPyruvic Acid - metabolismen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.subject.meshSarcoplasmic Reticulum Calcium-Transporting ATPases - metabolismen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshSuperoxides - metabolismen_HK
dc.subject.meshTyrosine - metabolismen_HK
dc.titleCardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stressen_HK
dc.typeArticleen_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1152/ajpcell.00137.2010en_HK
dc.identifier.pmid20573996-
dc.identifier.pmcidPMC2944313-
dc.identifier.scopuseid_2-s2.0-77956589569en_HK
dc.identifier.hkuros181811en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956589569&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume299en_HK
dc.identifier.issue3en_HK
dc.identifier.spageC643en_HK
dc.identifier.epageC653en_HK
dc.identifier.isiWOS:000281389100013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, WH=24399936100en_HK
dc.identifier.scopusauthoridCheng, WT=36655389700en_HK
dc.identifier.scopusauthoridKravtsov, GM=7003811092en_HK
dc.identifier.scopusauthoridTong, XY=23098731900en_HK
dc.identifier.scopusauthoridHou, XY=7402838794en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK

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