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Article: Repeated non-invasive limb ischemic preconditioning confers cardioprotection through PkC-ԑ/STAT3 signaling in diabetic rats
Title | Repeated non-invasive limb ischemic preconditioning confers cardioprotection through PkC-ԑ/STAT3 signaling in diabetic rats |
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Authors | |
Keywords | Diabetes Myocardial ischemia injury PKC-ε Repeated non-invasive limb ischemic preconditioning STAT3 |
Issue Date | 2018 |
Publisher | Karger 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? |
Abstract | BACKGROUND/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 Identifier | http://hdl.handle.net/10722/258355 |
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 0.733 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wang, C | - |
dc.contributor.author | Li, H | - |
dc.contributor.author | Wang, S | - |
dc.contributor.author | Mao, X | - |
dc.contributor.author | Yan, D | - |
dc.contributor.author | Wong, SCS | - |
dc.contributor.author | Xia, Z | - |
dc.contributor.author | Irwin, MG | - |
dc.date.accessioned | 2018-08-22T01:37:09Z | - |
dc.date.available | 2018-08-22T01:37:09Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Cellular Physiology and Biochemistry, 2018, v. 45 n. 5, p. 2107-2121 | - |
dc.identifier.issn | 1015-8987 | - |
dc.identifier.uri | http://hdl.handle.net/10722/258355 | - |
dc.description.abstract | BACKGROUND/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.language | eng | - |
dc.publisher | Karger Publishers Open Access. The Journal's web site is located at http://www.karger.com/CPB | - |
dc.relation.ispartof | Cellular Physiology and Biochemistry | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Diabetes | - |
dc.subject | Myocardial ischemia injury | - |
dc.subject | PKC-ε | - |
dc.subject | Repeated non-invasive limb ischemic preconditioning | - |
dc.subject | STAT3 | - |
dc.title | Repeated non-invasive limb ischemic preconditioning confers cardioprotection through PkC-ԑ/STAT3 signaling in diabetic rats | - |
dc.type | Article | - |
dc.identifier.email | Wong, SCS: wongstan@hku.hk | - |
dc.identifier.email | Xia, Z: zyxia@hkucc.hku.hk | - |
dc.identifier.email | Irwin, MG: mgirwin@hku.hk | - |
dc.identifier.authority | Wong, SCS=rp01789 | - |
dc.identifier.authority | Xia, Z=rp00532 | - |
dc.identifier.authority | Irwin, MG=rp00390 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1159/000488047 | - |
dc.identifier.pmid | 29533954 | - |
dc.identifier.scopus | eid_2-s2.0-85044787406 | - |
dc.identifier.hkuros | 287324 | - |
dc.identifier.hkuros | 299975 | - |
dc.identifier.volume | 45 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | 2107 | - |
dc.identifier.epage | 2121 | - |
dc.identifier.isi | WOS:000428950000032 | - |
dc.publisher.place | Switzerland | - |
dc.identifier.issnl | 1015-8987 | - |