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Conference Paper: Antioxidants N-acetylcysterine and Allopurinol synergistically enhance cardiac HIF-1α and heme oxygenase-1 and attenuate Postischemic Myocardial Injury in diabetic rats

TitleAntioxidants N-acetylcysterine and Allopurinol synergistically enhance cardiac HIF-1α and heme oxygenase-1 and attenuate Postischemic Myocardial Injury in diabetic rats
Authors
KeywordsBiology
Issue Date2012
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
Experimental Biology Annual Meeting (EB 2012), San Diego, CA., 21-25 April 2012. In The FASEB Journal, 2012, v. 26 Meeting abstracts suppl., abstract no. 1114.3 How to Cite?
AbstractHypoxia inducible factor 1(HIF) α can reduce myocardial ischemia-reperfusion injury(MIRI). However, hyperglycemia-induced oxidative stress may reduce cardiac HIF-1α and subsequently inhibit heme oxygenase 1 (HO-1), a down-stream protein of HIF-1α that has anti-ischemic properties. N-acetylcysteine (NAC) and allopurinol (ALP) synergistically reduce MIRI in diabetes (PLoS One. 2011;6:e23967), but the role of HIF-1α/HO-1 in this process in unknown. Control or streptozotocin (STZ)-induced diabetic rats were untreated (C, D) or treated with NAC (1.5g/kg/day) or ALP (100 mg/kg/day) or their combination (NAC+ALP) for four weeks starting one week after STZ injection. Cardiac and plasma 15-F2t-isoprostane (IsoP) were increased in D rats while cardiac HO-1 and protein expression and activity were reduced, accompanied with reduced cardiac HIF-1α, and increased post-ischemic myocardial infarct size (IS) and cellular injury in D rats subjected to 30 minutes of coronary artery occlusion and 2 hours of reperfusion (all P<0.05 D vs. C). NAC+ALP normalized cardiac levels of HO-1 and HIF-1α protein expression, prevented the increase in IsoP, and reduced myocardial IS, but these effects of NAC+ALP were cancelled by either the HO-1 blocker protoporphyrin or the HIF-1α blocker 2-Methoxyestradiol. It is concluded that HIF-1α and HO-1 activation play an important role in NAC and ALP mediated cardioprotection in diabetes.
DescriptionOpen Access Journal
Persistent Identifierhttp://hdl.handle.net/10722/160421
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorMao, Xen_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorWang, Ten_US
dc.contributor.authorLei, Sen_US
dc.contributor.authorIrwin, MGen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorXia, Zen_US
dc.date.accessioned2012-08-16T06:10:47Z-
dc.date.available2012-08-16T06:10:47Z-
dc.date.issued2012en_US
dc.identifier.citationExperimental Biology Annual Meeting (EB 2012), San Diego, CA., 21-25 April 2012. In The FASEB Journal, 2012, v. 26 Meeting abstracts suppl., abstract no. 1114.3en_US
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/160421-
dc.descriptionOpen Access Journal-
dc.description.abstractHypoxia inducible factor 1(HIF) α can reduce myocardial ischemia-reperfusion injury(MIRI). However, hyperglycemia-induced oxidative stress may reduce cardiac HIF-1α and subsequently inhibit heme oxygenase 1 (HO-1), a down-stream protein of HIF-1α that has anti-ischemic properties. N-acetylcysteine (NAC) and allopurinol (ALP) synergistically reduce MIRI in diabetes (PLoS One. 2011;6:e23967), but the role of HIF-1α/HO-1 in this process in unknown. Control or streptozotocin (STZ)-induced diabetic rats were untreated (C, D) or treated with NAC (1.5g/kg/day) or ALP (100 mg/kg/day) or their combination (NAC+ALP) for four weeks starting one week after STZ injection. Cardiac and plasma 15-F2t-isoprostane (IsoP) were increased in D rats while cardiac HO-1 and protein expression and activity were reduced, accompanied with reduced cardiac HIF-1α, and increased post-ischemic myocardial infarct size (IS) and cellular injury in D rats subjected to 30 minutes of coronary artery occlusion and 2 hours of reperfusion (all P<0.05 D vs. C). NAC+ALP normalized cardiac levels of HO-1 and HIF-1α protein expression, prevented the increase in IsoP, and reduced myocardial IS, but these effects of NAC+ALP were cancelled by either the HO-1 blocker protoporphyrin or the HIF-1α blocker 2-Methoxyestradiol. It is concluded that HIF-1α and HO-1 activation play an important role in NAC and ALP mediated cardioprotection 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-acetylcysterine and Allopurinol synergistically enhance cardiac HIF-1α and heme oxygenase-1 and attenuate Postischemic Myocardial Injury in diabetic ratsen_US
dc.typeConference_Paperen_US
dc.identifier.emailLiu, Y: yanan@hku.hken_US
dc.identifier.emailWang, T: wangtt6@hku.hken_US
dc.identifier.emailLei, S: shqlei@hku.hken_US
dc.identifier.emailIrwin, MG: mgirwin@hku.hken_US
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_US
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityIrwin, MG=rp00390en_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.identifier.authorityXia, Z=rp00532en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros205200en_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. 1114.3-

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