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Article: N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes

TitleN-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes
Authors
KeywordsAdiponectin
Antioxidants
Diabetes
Jak2/STAT3
Myocardial ischemia injury
PI3K/Akt
Issue Date2013
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed
Citation
Free Radical Biology & Medicine, 2013, v. 63, p. 291-303 How to Cite?
AbstractN-Acetylcysteine (NAC) and allopurinol (ALP) synergistically reduce myocardial ischemia reperfusion (MI/R) injury in diabetes. However, the mechanism is unclear. We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. Control (C) or streptozotocin-induced diabetic rats (D) were untreated or treated with NAC and ALP followed by MI/R. D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process.
Persistent Identifierhttp://hdl.handle.net/10722/184328
ISSN
2015 Impact Factor: 5.784
2015 SCImago Journal Rankings: 2.468
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, T-
dc.contributor.authorMao, X-
dc.contributor.authorLi, H-
dc.contributor.authorQiao, S-
dc.contributor.authorXu, A-
dc.contributor.authorWang, JJ-
dc.contributor.authorLei, S-
dc.contributor.authorLiu, Z-
dc.contributor.authorNg, JKF-
dc.contributor.authorWong, GTC-
dc.contributor.authorVanhoutte, PMGR-
dc.contributor.authorIrwin, MG-
dc.contributor.authorXia, Z-
dc.date.accessioned2013-07-11T02:43:20Z-
dc.date.available2013-07-11T02:43:20Z-
dc.date.issued2013-
dc.identifier.citationFree Radical Biology & Medicine, 2013, v. 63, p. 291-303-
dc.identifier.issn0891-5849-
dc.identifier.urihttp://hdl.handle.net/10722/184328-
dc.description.abstractN-Acetylcysteine (NAC) and allopurinol (ALP) synergistically reduce myocardial ischemia reperfusion (MI/R) injury in diabetes. However, the mechanism is unclear. We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. Control (C) or streptozotocin-induced diabetic rats (D) were untreated or treated with NAC and ALP followed by MI/R. D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed-
dc.relation.ispartofFree Radical Biology & Medicine-
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Free Radical Biology & Medicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Free Radical Biology & Medicine, [VOL 63, ISSUE#, 2013] DOI 10.1016/j.freeradbiomed.2013.05.043-
dc.subjectAdiponectin-
dc.subjectAntioxidants-
dc.subjectDiabetes-
dc.subjectJak2/STAT3-
dc.subjectMyocardial ischemia injury-
dc.subjectPI3K/Akt-
dc.titleN-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetesen_US
dc.typeArticleen_US
dc.identifier.emailWang, JJ: junwen@hkucc.hku.hk-
dc.identifier.emailNg, JKF: jkfng@hkucc.hku.hk-
dc.identifier.emailWong, GTC: gordontcwong@hotmail.com-
dc.identifier.emailVanhoutte, PMGR: vanhoutt@hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hkucc.hku.hk-
dc.identifier.emailXia, Z: zhengyuan_xia@yahoo.com-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.freeradbiomed.2013.05.043-
dc.identifier.pmid23747931-
dc.identifier.scopuseid_2-s2.0-84879473184-
dc.identifier.hkuros221749-
dc.identifier.hkuros216275-
dc.identifier.hkuros261669-
dc.identifier.volume63-
dc.identifier.spage291-
dc.identifier.epage303-
dc.identifier.isiWOS:000323094700028-
dc.publisher.placeUnited States-

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