File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Repeated non-invasive limb ischemic preconditioning confers cardioprotection through PkC-ε/STAT3 signaling in diabetic rats

TitleRepeated non-invasive limb ischemic preconditioning confers cardioprotection through PkC-ε/STAT3 signaling in diabetic rats
Other TitlesRepeated non-invasive limb ischemic preconditioning confers cardioprotection through PKC-epsilon/STAT3 signaling in diabetic rats
Authors
KeywordsDiabetes
Myocardial ischemia injury
PKC-ε
Repeated non-invasive limb ischemic preconditioning
STAT3
Issue Date2018
PublisherKarger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB
Citation
Cellular Physiology and Biochemistry, 2018, v. 45 n. 5, p. 2107-2121 How to Cite?
AbstractBACKGROUND/AIMS: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. METHODS: Eight-week streptozotocin-induced diabetic and non-diabetic Sprague-Dawley rats were subjected to I/R without or with rNLIP. In vitro, H9C2 cells were cultured with high glucose (HG) and subjected to hypoxia/re-oxygenation (H/R) without or with PKC-ε or STAT3 gene knock-down in the absence or presence of remote time hypoxia preconditioning (HPC). RESULTS: Diabetic rats displayed larger post-ischemic myocardial infarct size and higher troponin-I release with concomitant cardiac PKC-ԑ overexpression and activation manifested as increased membrane translocation, while phosphorylated STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size in both non-diabetic and diabetic rats. rNLIP reduced post-ischemic cardiac PKC-ԑ activation in diabetic while increased PKC-ԑ activation in non-diabetic rats, resulting in increased cardiac p-STAT3 and p-Akt. In H9C2 cells, HG increased PKC-ԑ expression and exacerbated post-H/R injury, accompanied with reduced p-STAT3 and p-Akt, which were all reverted by HPC. These HPC protective effects were abolished by either PKC-ԑ or STAT3 gene knock-down, except that PKC-ԑ gene knock-down reverted HG and H/R-induced reduction of p-STAT3. CONCLUSION: rNLIP attenuates diabetic heart I/R injury by mitigating HG-induced PKC-ԑ overexpression and, subsequently, activating STAT3.
Persistent Identifierhttp://hdl.handle.net/10722/258355
ISSN
2017 Impact Factor: 5.5
2015 SCImago Journal Rankings: 1.139
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, C-
dc.contributor.authorLi, H-
dc.contributor.authorWang, S-
dc.contributor.authorMao, X-
dc.contributor.authorYan, D-
dc.contributor.authorWong, SCS-
dc.contributor.authorXia, Z-
dc.contributor.authorIrwin, MG-
dc.date.accessioned2018-08-22T01:37:09Z-
dc.date.available2018-08-22T01:37:09Z-
dc.date.issued2018-
dc.identifier.citationCellular Physiology and Biochemistry, 2018, v. 45 n. 5, p. 2107-2121-
dc.identifier.issn1015-8987-
dc.identifier.urihttp://hdl.handle.net/10722/258355-
dc.description.abstractBACKGROUND/AIMS: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. METHODS: Eight-week streptozotocin-induced diabetic and non-diabetic Sprague-Dawley rats were subjected to I/R without or with rNLIP. In vitro, H9C2 cells were cultured with high glucose (HG) and subjected to hypoxia/re-oxygenation (H/R) without or with PKC-ε or STAT3 gene knock-down in the absence or presence of remote time hypoxia preconditioning (HPC). RESULTS: Diabetic rats displayed larger post-ischemic myocardial infarct size and higher troponin-I release with concomitant cardiac PKC-ԑ overexpression and activation manifested as increased membrane translocation, while phosphorylated STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size in both non-diabetic and diabetic rats. rNLIP reduced post-ischemic cardiac PKC-ԑ activation in diabetic while increased PKC-ԑ activation in non-diabetic rats, resulting in increased cardiac p-STAT3 and p-Akt. In H9C2 cells, HG increased PKC-ԑ expression and exacerbated post-H/R injury, accompanied with reduced p-STAT3 and p-Akt, which were all reverted by HPC. These HPC protective effects were abolished by either PKC-ԑ or STAT3 gene knock-down, except that PKC-ԑ gene knock-down reverted HG and H/R-induced reduction of p-STAT3. CONCLUSION: rNLIP attenuates diabetic heart I/R injury by mitigating HG-induced PKC-ԑ overexpression and, subsequently, activating STAT3.-
dc.languageeng-
dc.publisherKarger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB-
dc.relation.ispartofCellular Physiology and Biochemistry-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDiabetes-
dc.subjectMyocardial ischemia injury-
dc.subjectPKC-ε-
dc.subjectRepeated non-invasive limb ischemic preconditioning-
dc.subjectSTAT3-
dc.titleRepeated non-invasive limb ischemic preconditioning confers cardioprotection through PkC-ε/STAT3 signaling in diabetic rats-
dc.title.alternativeRepeated non-invasive limb ischemic preconditioning confers cardioprotection through PKC-epsilon/STAT3 signaling in diabetic rats-
dc.typeArticle-
dc.identifier.emailWong, SCS: wongstan@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hku.hk-
dc.identifier.authorityWong, SCS=rp01789-
dc.identifier.authorityXia, Z=rp00532-
dc.identifier.authorityIrwin, MG=rp00390-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1159/000488047-
dc.identifier.pmid29533954-
dc.identifier.hkuros287324-
dc.identifier.hkuros299975-
dc.identifier.volume45-
dc.identifier.issue5-
dc.identifier.spage2107-
dc.identifier.epage2121-
dc.identifier.isiWOS:000428950000032-
dc.publisher.placeSwitzerland-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats