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Conference Paper: Antioxidants N-Acetylcysteine and Allopurinol attenuation of postischemic myocardial injury in diabetic rats involve Akt and STAT3 mediated eNOS activation

TitleAntioxidants N-Acetylcysteine and Allopurinol attenuation of postischemic myocardial injury in diabetic rats involve Akt and STAT3 mediated eNOS activation
Authors
KeywordsBiology
Issue Date2012
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
The 2012 Annual Meeting of Experimental Biology (EB 2012), San Diego, CA., 21-25 April 2012. In The FASEB Journal, 2012, v. 26 meeting abstracts suppl., abstract no. 1117.1 How to Cite?
AbstractHyperglycemia-induced oxidative stress exacerbates myocardial ischemic reperfusion (MI/R) injury. N-acetylcysteine (NAC) and allopurinol (ALP) reduced MI/R injury in streptozotocin (STZ)-induced diabetes (PLoS One. 2011;6:e23967), but the mechanism is unclear. We postulated that NAC and ALP attenuate MI/R injury via PI3k/Akt and Jak2/STAT3 mediated eNOS activation in diabetes. Control (C) or STZ-induced diabetic (D) rats were untreated or treated with NAC (1.5g/kg/day) or ALP (100 mg/kg/day) or their combination for four weeks starting one week after STZ injection. NAC and ALP synergistically decreased myocardial infarct size in D rats subjected to 30 minutes of coronary artery occlusion and 2 hours reperfusion, and restored phosphorylations of cardiac Akt, STAT3 and eNOS (P<0.05 NAC+ALP vs. D). Exposure of rat cardiomyocytes to high glucose and 45 min hypoxia and 2 hours reoxygenation induced post-hypoxic cell death reflected as increase of lactate dehydrogenase leakage and reduced cell viability. NAC and ALP synergistically reduced post-hypoxic cell death and enhanced phosphorylations of Akt, STAT3 and eNOS. The PI3K inhibitor wortmannin and Jak2 inhibitor AG490, respectively attenuated NAC and ALP’s protective effects in vivo and in vitro. We conclude that activation of both the PI3K/Akt and the Jak2/STAT3 signaling are involved in NAC and ALP mediated attenuation of MI/R injury in diabetes.
DescriptionOpen Access Journal
Persistent Identifierhttp://hdl.handle.net/10722/160565
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorWang, Ten_US
dc.contributor.authorMao, Xen_US
dc.contributor.authorQiao, Sen_US
dc.contributor.authorLei, Sen_US
dc.contributor.authorNg, JKFen_US
dc.contributor.authorIrwin, MGen_US
dc.contributor.authorXia, Zen_US
dc.date.accessioned2012-08-16T06:14:24Z-
dc.date.available2012-08-16T06:14:24Z-
dc.date.issued2012en_US
dc.identifier.citationThe 2012 Annual Meeting of Experimental Biology (EB 2012), San Diego, CA., 21-25 April 2012. In The FASEB Journal, 2012, v. 26 meeting abstracts suppl., abstract no. 1117.1en_US
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/160565-
dc.descriptionOpen Access Journal-
dc.description.abstractHyperglycemia-induced oxidative stress exacerbates myocardial ischemic reperfusion (MI/R) injury. N-acetylcysteine (NAC) and allopurinol (ALP) reduced MI/R injury in streptozotocin (STZ)-induced diabetes (PLoS One. 2011;6:e23967), but the mechanism is unclear. We postulated that NAC and ALP attenuate MI/R injury via PI3k/Akt and Jak2/STAT3 mediated eNOS activation in diabetes. Control (C) or STZ-induced diabetic (D) rats were untreated or treated with NAC (1.5g/kg/day) or ALP (100 mg/kg/day) or their combination for four weeks starting one week after STZ injection. NAC and ALP synergistically decreased myocardial infarct size in D rats subjected to 30 minutes of coronary artery occlusion and 2 hours reperfusion, and restored phosphorylations of cardiac Akt, STAT3 and eNOS (P<0.05 NAC+ALP vs. D). Exposure of rat cardiomyocytes to high glucose and 45 min hypoxia and 2 hours reoxygenation induced post-hypoxic cell death reflected as increase of lactate dehydrogenase leakage and reduced cell viability. NAC and ALP synergistically reduced post-hypoxic cell death and enhanced phosphorylations of Akt, STAT3 and eNOS. The PI3K inhibitor wortmannin and Jak2 inhibitor AG490, respectively attenuated NAC and ALP’s protective effects in vivo and in vitro. We conclude that activation of both the PI3K/Akt and the Jak2/STAT3 signaling are involved in NAC and ALP mediated attenuation of MI/R injury in diabetes.-
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/-
dc.relation.ispartofThe FASEB Journalen_US
dc.subjectBiology-
dc.titleAntioxidants N-Acetylcysteine and Allopurinol attenuation of postischemic myocardial injury in diabetic rats involve Akt and STAT3 mediated eNOS activationen_US
dc.typeConference_Paperen_US
dc.identifier.emailWang, T: wangtt6@hku.hken_US
dc.identifier.emailQiao, S: qiao1983@hku.hken_US
dc.identifier.emailLei, S: shqlei@hku.hken_US
dc.identifier.emailNg, JKF: jkfng@hku.hken_US
dc.identifier.emailIrwin, MG: mgirwin@hku.hken_US
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hken_US
dc.identifier.authorityNg, JKF=rp00544en_US
dc.identifier.authorityIrwin, MG=rp00390en_US
dc.identifier.authorityXia, Z=rp00532en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros205204en_US
dc.identifier.volume26en_US
dc.identifier.issuemeeting abstracts suppl.-
dc.publisher.placeUnited States-
dc.description.otherExperimental Biology Annual Meeting (EB 2012), San Diego, CA., 21-25 April 2012. In The FASEB Journal, 2012, v. 26 Meeting abstracts suppl., abstract no. 1117.1-

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