Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats.
Gαq protein carboxyl terminus imitation polypeptide (GCIP)-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4379177?pdf=render |
| _version_ | 1828234078289133568 |
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| author | Xiao Lan Lu Yang Fei Tong Ya Liu Ya Li Xu Hua Yang Guo Yuan Zhang Xiao-Hui Li Hai-Gang Zhang |
| author_facet | Xiao Lan Lu Yang Fei Tong Ya Liu Ya Li Xu Hua Yang Guo Yuan Zhang Xiao-Hui Li Hai-Gang Zhang |
| author_sort | Xiao Lan Lu |
| collection | DOAJ |
| description | Gαq protein carboxyl terminus imitation polypeptide (GCIP)-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function. This study was designed to investigate the effects of GCIP-27 on heart function in rats with heart failure induced by doxorubicin.Forty-eight rats were randomly divided into the following six groups receiving vehicle (control), doxorubicin (Dox), losartan (6 mg/kg, i.g.) and three doses of GCIP-27 (10, 30, 90 μg/kg; i.p., bid), respectively. Heart failure was induced by Dox, which was administered at a 20 mg/kg cumulative dose. After 10 weeks of treatment, we observed that GCIP-27 (30, 90 μg/kg) significantly increased ejection fraction, fraction shortening, stroke volume and sarcoplasmic reticulum Ca2+ ATPase activity of Dox-treated hearts. Additionally, GCIP-27 decreased myocardial injury, heart weight index and left ventricular weight index, fibrosis and serum cardiac troponin-I concentration in Dox-treated mice. Immunohistochemistry, western blotting and real-time PCR experiments indicated that GCIP-27 (10-90 μg/kg) could markedly upregulate the protein expression of myocardial α-myosin heavy chain (MHC), Bcl-2, protein kinase C (PKC) ε and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 as well as the mRNA expression of α-MHC, but downregulated the expression of β-MHC, Bax and PKC βII, and the mRNA expression levels of β-MHC in Dox-treated mice. It was also found that GCIP-27 (30, 90 μg/L) decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group.GCIP-27 could effectively ameliorate heart failure development induced by Dox. PKC-ERK1/2 signaling might represent the underlying mechanism of the beneficial effects of GCIP-27. |
| first_indexed | 2024-04-12T19:49:27Z |
| format | Article |
| id | doaj.art-08fdff21ce3d4478b42f78ff30d06169 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T19:49:27Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-08fdff21ce3d4478b42f78ff30d061692022-12-22T03:18:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012100710.1371/journal.pone.0121007Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats.Xiao Lan LuYang Fei TongYa LiuYa Li XuHua YangGuo Yuan ZhangXiao-Hui LiHai-Gang ZhangGαq protein carboxyl terminus imitation polypeptide (GCIP)-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function. This study was designed to investigate the effects of GCIP-27 on heart function in rats with heart failure induced by doxorubicin.Forty-eight rats were randomly divided into the following six groups receiving vehicle (control), doxorubicin (Dox), losartan (6 mg/kg, i.g.) and three doses of GCIP-27 (10, 30, 90 μg/kg; i.p., bid), respectively. Heart failure was induced by Dox, which was administered at a 20 mg/kg cumulative dose. After 10 weeks of treatment, we observed that GCIP-27 (30, 90 μg/kg) significantly increased ejection fraction, fraction shortening, stroke volume and sarcoplasmic reticulum Ca2+ ATPase activity of Dox-treated hearts. Additionally, GCIP-27 decreased myocardial injury, heart weight index and left ventricular weight index, fibrosis and serum cardiac troponin-I concentration in Dox-treated mice. Immunohistochemistry, western blotting and real-time PCR experiments indicated that GCIP-27 (10-90 μg/kg) could markedly upregulate the protein expression of myocardial α-myosin heavy chain (MHC), Bcl-2, protein kinase C (PKC) ε and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 as well as the mRNA expression of α-MHC, but downregulated the expression of β-MHC, Bax and PKC βII, and the mRNA expression levels of β-MHC in Dox-treated mice. It was also found that GCIP-27 (30, 90 μg/L) decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group.GCIP-27 could effectively ameliorate heart failure development induced by Dox. PKC-ERK1/2 signaling might represent the underlying mechanism of the beneficial effects of GCIP-27.http://europepmc.org/articles/PMC4379177?pdf=render |
| spellingShingle | Xiao Lan Lu Yang Fei Tong Ya Liu Ya Li Xu Hua Yang Guo Yuan Zhang Xiao-Hui Li Hai-Gang Zhang Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats. PLoS ONE |
| title | Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats. |
| title_full | Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats. |
| title_fullStr | Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats. |
| title_full_unstemmed | Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats. |
| title_short | Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats. |
| title_sort | gαq protein carboxyl terminus imitation polypeptide gcip 27 improves cardiac function in chronic heart failure rats |
| url | http://europepmc.org/articles/PMC4379177?pdf=render |
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