open access

Vol 24, No 4 (2017)
Original articles — Basic science and experimental cardiology
Published online: 2017-02-07
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Sevoflurane ameliorates doxorubicin-induced myocardial injury by affecting the phosphorylation states of proteins in PI3K/Akt/mTOR signaling pathway

Yini Wu, Jianping Wang, Xiaoyan Yu, Dongli Li, Xin Han, Lihua Fan
DOI: 10.5603/CJ.a2017.0018
·
Pubmed: 28198521
·
Cardiol J 2017;24(4):409-418.

open access

Vol 24, No 4 (2017)
Original articles — Basic science and experimental cardiology
Published online: 2017-02-07

Abstract

Background: The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mam­malian target of rapamycin (mTOR) signaling pathway.

Methods: Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-μL saline solution), sevoflurane group (SevG, inhaled with 2.4% sevoflurane for 2 h), LY294002 group (LYG, Akt inhibitor, 0.3 mg/kg in 200-μL Dimethyl Sulfoxide [DMSO]), solvent DMSO control group (SG) and autophagy inhibitor 3-methyladenine (3-MA) group (MG, 30 mg/kg in 200-μL DMSO). The healthy rats were assigned to a contro1 group (CG, 200-μL saline solution). Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The concentration of cardiac troponin I (cTnI) was detected by ELISA. The levels of total Akt (t-Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated-mTOR (p-mTOR) and autophagy marker LC3-II was detected by Western Blot. The experiments were also repeated at the cell level. Results: Terminal deoxynucleotidyl transferase dUTP nick end labeling analysis showed that the ap­optosis rates were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG. The levels of p-Akt p-mTOR were low in groups DG and SG, reached the lowest level in LYG, increased in SevG and MG, and reached the highest level in CG. In contrast, LC3-II expression, apoptosis index and serum cTnI concentration were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG (p < 0.05). Cell experiment showed similar results as with animal experiments.

Conclusions: Sevoflurane ameliorates myocardial injury by affecting the phosphorylation states of the proteins in PI3K/Akt/mTOR signaling pathway and reducing the injury biomarker. (Cardiol J 2017; 24, 4: 409–418)

Abstract

Background: The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mam­malian target of rapamycin (mTOR) signaling pathway.

Methods: Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-μL saline solution), sevoflurane group (SevG, inhaled with 2.4% sevoflurane for 2 h), LY294002 group (LYG, Akt inhibitor, 0.3 mg/kg in 200-μL Dimethyl Sulfoxide [DMSO]), solvent DMSO control group (SG) and autophagy inhibitor 3-methyladenine (3-MA) group (MG, 30 mg/kg in 200-μL DMSO). The healthy rats were assigned to a contro1 group (CG, 200-μL saline solution). Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The concentration of cardiac troponin I (cTnI) was detected by ELISA. The levels of total Akt (t-Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated-mTOR (p-mTOR) and autophagy marker LC3-II was detected by Western Blot. The experiments were also repeated at the cell level. Results: Terminal deoxynucleotidyl transferase dUTP nick end labeling analysis showed that the ap­optosis rates were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG. The levels of p-Akt p-mTOR were low in groups DG and SG, reached the lowest level in LYG, increased in SevG and MG, and reached the highest level in CG. In contrast, LC3-II expression, apoptosis index and serum cTnI concentration were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG (p < 0.05). Cell experiment showed similar results as with animal experiments.

Conclusions: Sevoflurane ameliorates myocardial injury by affecting the phosphorylation states of the proteins in PI3K/Akt/mTOR signaling pathway and reducing the injury biomarker. (Cardiol J 2017; 24, 4: 409–418)

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Keywords

cardiac injury, doxorubicin, phosphatidylinositol 3-kinase, phosphorylated rapamycin, protein-serine-threonine kinases

About this article
Title

Sevoflurane ameliorates doxorubicin-induced myocardial injury by affecting the phosphorylation states of proteins in PI3K/Akt/mTOR signaling pathway

Journal

Cardiology Journal

Issue

Vol 24, No 4 (2017)

Pages

409-418

Published online

2017-02-07

DOI

10.5603/CJ.a2017.0018

Pubmed

28198521

Bibliographic record

Cardiol J 2017;24(4):409-418.

Keywords

cardiac injury
doxorubicin
phosphatidylinositol 3-kinase
phosphorylated rapamycin
protein-serine-threonine kinases

Authors

Yini Wu
Jianping Wang
Xiaoyan Yu
Dongli Li
Xin Han
Lihua Fan

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