Repeated Non-Invasive Limb Ischemic Preconditioning Confers Cardioprotection Through PKC-Ô/STAT3 Signaling in Diabetic Rats.
Cell Physiol Biochem
; 45(5): 2107-2121, 2018.
Article
em En
| MEDLINE
| ID: mdl-29533954
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-Ô 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-Ô activation in diabetic while increased PKC-Ô activation in non-diabetic rats, resulting in increased cardiac p-STAT3 and p-Akt. In H9C2 cells, HG increased PKC-Ô 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-Ô or STAT3 gene knock-down, except that PKC-Ô 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-Ô overexpression and, subsequently, activating STAT3.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
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Diabetes Mellitus Experimental
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Proteína Quinase C-épsilon
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Fator de Transcrição STAT3
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article