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Article: Polyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteins

TitlePolyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteins
Authors
KeywordsAldose reductase
Calcium handling activity
Myocardial ischemia and reperfusion
Oxidative stress
Polyol pathway
Ryanodine receptor
S-glutathiolation
Sacro/endoplasmic reticulum Ca2+-ATPase
Sorbitol dehydrogenase
Tyrosine nitration
Issue Date2010
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmcc
Citation
Journal Of Molecular And Cellular Cardiology, 2010, v. 49 n. 1, p. 58-69 How to Cite?
AbstractA number of studies have shown that the polyol pathway, consisting of aldose reductase (AR) and sorbitol dehydrogenase (SDH), contributes to ischemia-reperfusion (I/R)-induced myocardial infarction due to depletion of ATP. In this report we show that the polyol pathway in I/R heart also contributes to the impairment of sacro/endoplasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR), two key players in Ca2+ signaling that regulate cardiac contraction. Rat hearts were isolated and retrogradely perfused with either Krebs' buffer containing 1 ?M AR inhibitor, zopolrestat, or 200 nM SDH inhibitor, CP-170,711, and challenged by 30 min of regional ischemia and 45 min of reperfusion. We found that post-ischemic contractile function of the isolated perfused hearts was improved by pharmacological inhibition of the polyol pathway. I/R-induced contractile dysfunction is most likely due to impairment in Ca2+ signaling and the activities of SERCA and RyR. All these abnormalities were significantly ameliorated by treatment with ARI or SDI. We showed that the polyol pathway activities increase the level of peroxynitrite, which enhances the tyrosine nitration of SERCA and irreversibly modifies it to form SERCAC674-SO3H. This leads to reduced level of S-glutathiolated SERCA, contributing to its inactivation. The polyol pathway activities also deplete the level of GSH, leading to decreased active RyR, the S-glutathiolated RyR. Thus, in I/R heart, inhibition of polyol pathway improved the function of SERCA and RyR by protecting them from irreversible oxidation. © 2009 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/124481
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.522
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIHRO1 HL31607-25
Funding Information:

We thank C.P. Mok and Dr S. Wu for their technical assistance. XT and XH were supported by NIH grant RO1 HL31607-25 We would like to thank Prof Richard A. Cohen for critical reading of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorTang, WHen_HK
dc.contributor.authorKravtsov, GMen_HK
dc.contributor.authorSauert, Men_HK
dc.contributor.authorTong, XYen_HK
dc.contributor.authorHou, XYen_HK
dc.contributor.authorWong, TMen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorMan Chung, SSen_HK
dc.date.accessioned2010-10-31T10:36:49Z-
dc.date.available2010-10-31T10:36:49Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Molecular And Cellular Cardiology, 2010, v. 49 n. 1, p. 58-69en_HK
dc.identifier.issn0022-2828en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124481-
dc.description.abstractA number of studies have shown that the polyol pathway, consisting of aldose reductase (AR) and sorbitol dehydrogenase (SDH), contributes to ischemia-reperfusion (I/R)-induced myocardial infarction due to depletion of ATP. In this report we show that the polyol pathway in I/R heart also contributes to the impairment of sacro/endoplasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR), two key players in Ca2+ signaling that regulate cardiac contraction. Rat hearts were isolated and retrogradely perfused with either Krebs' buffer containing 1 ?M AR inhibitor, zopolrestat, or 200 nM SDH inhibitor, CP-170,711, and challenged by 30 min of regional ischemia and 45 min of reperfusion. We found that post-ischemic contractile function of the isolated perfused hearts was improved by pharmacological inhibition of the polyol pathway. I/R-induced contractile dysfunction is most likely due to impairment in Ca2+ signaling and the activities of SERCA and RyR. All these abnormalities were significantly ameliorated by treatment with ARI or SDI. We showed that the polyol pathway activities increase the level of peroxynitrite, which enhances the tyrosine nitration of SERCA and irreversibly modifies it to form SERCAC674-SO3H. This leads to reduced level of S-glutathiolated SERCA, contributing to its inactivation. The polyol pathway activities also deplete the level of GSH, leading to decreased active RyR, the S-glutathiolated RyR. Thus, in I/R heart, inhibition of polyol pathway improved the function of SERCA and RyR by protecting them from irreversible oxidation. © 2009 Elsevier Ltd.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmccen_HK
dc.relation.ispartofJournal of Molecular and Cellular Cardiologyen_HK
dc.subjectAldose reductaseen_HK
dc.subjectCalcium handling activityen_HK
dc.subjectMyocardial ischemia and reperfusionen_HK
dc.subjectOxidative stressen_HK
dc.subjectPolyol pathwayen_HK
dc.subjectRyanodine receptoren_HK
dc.subjectS-glutathiolationen_HK
dc.subjectSacro/endoplasmic reticulum Ca2+-ATPaseen_HK
dc.subjectSorbitol dehydrogenaseen_HK
dc.subjectTyrosine nitrationen_HK
dc.titlePolyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteinsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2828&volume=49&issue=1&spage=58&epage=69&date=2010&atitle=Polyol+pathway+impairs+the+function+of+SERCA+and+RyR+in+ischemic-reperfused+rat+hearts+by+increasing+oxidative+modificaitons+of+these+proteinsen_HK
dc.identifier.emailChung, SK:skchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.yjmcc.2009.12.003en_HK
dc.identifier.pmid20025885-
dc.identifier.pmcidPMC3043380-
dc.identifier.scopuseid_2-s2.0-77953476519en_HK
dc.identifier.hkuros181791en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953476519&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue1en_HK
dc.identifier.spage58en_HK
dc.identifier.epage69en_HK
dc.identifier.isiWOS:000278750300008-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTang, WH=24399936100en_HK
dc.identifier.scopusauthoridKravtsov, GM=7003811092en_HK
dc.identifier.scopusauthoridSauert, M=36497280400en_HK
dc.identifier.scopusauthoridTong, XY=23098731900en_HK
dc.identifier.scopusauthoridHou, XY=7402838794en_HK
dc.identifier.scopusauthoridWong, TM=7403531434en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridMan Chung, SS=35264547000en_HK
dc.identifier.citeulike6412072-

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