Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats
To understand the mechanism underlying the regression of cardiac hypertrophy, we investigated the pathological changes after isoproterenol (ISO) withdrawal in ISO-induced cardiomyopathy models in rats and neonatal cardiomyocytes. Cardiac hypertrophy was induced in rats by two weeks of ISO administra...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861320300657 |
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| author | Jingyuan Li Qinghua Gao Siqi Wang Ze Kang Zhuo Li Shuai Lei Xuefei Sun Meimi Zhao Xiye Chen Guangyu Jiao Huiyuan Hu Liying Hao |
| author_facet | Jingyuan Li Qinghua Gao Siqi Wang Ze Kang Zhuo Li Shuai Lei Xuefei Sun Meimi Zhao Xiye Chen Guangyu Jiao Huiyuan Hu Liying Hao |
| author_sort | Jingyuan Li |
| collection | DOAJ |
| description | To understand the mechanism underlying the regression of cardiac hypertrophy, we investigated the pathological changes after isoproterenol (ISO) withdrawal in ISO-induced cardiomyopathy models in rats and neonatal cardiomyocytes. Cardiac hypertrophy was induced in rats by two weeks of ISO administration; however, the hypertrophy did not regress after three weeks of natural maintenance after ISO administration was withdrawn (ISO-wdr group). The remaining hypertrophy in the ISO-wdr group was accompanied by a sustained increase in the level of phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII). Additionally, the increased expression levels of histone deacetylase 4 (HDAC4) and the CaV1.2 channel and amounts of CaMKII bound with HDAC4 and CaV1.2 were not recovered in the ISO-wdr group. The results in cardiomyocyte models were similar to those seen in rat models. Losartan, metoprolol or amlodipine neither ameliorated the increase in atrial natriuretic peptide nor inhibited the increase in p-CaMKII and bound CaMKII. In contrast, autocamtide-2-related inhibitor peptide, a CaMKII inhibitor, reduced these increases. This study investigated the phosphorylation status of CaMKII after hypertrophic stimulus was withdrawn for the first time and proposed that CaMKII as well as its complexes with CaV1.2 could be potential targets to achieve effective regression of cardiac hypertrophy. |
| first_indexed | 2024-12-13T05:50:13Z |
| format | Article |
| id | doaj.art-17f06f195f894fa68612b8332a63b4bf |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-13T05:50:13Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-17f06f195f894fa68612b8332a63b4bf2022-12-21T23:57:34ZengElsevierJournal of Pharmacological Sciences1347-86132020-09-0114413042Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in ratsJingyuan Li0Qinghua Gao1Siqi Wang2Ze Kang3Zhuo Li4Shuai Lei5Xuefei Sun6Meimi Zhao7Xiye Chen8Guangyu Jiao9Huiyuan Hu10Liying Hao11Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 8908544, Japan; Department of Physiology, School of Life Sciences, China Medical University, Shenyang, 110001, China; Corresponding author. Department of Physiology, Graduate Schoool of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 8908544, Japan.Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, 110001, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, ChinaDepartment of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, China; Corresponding author. Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, China.To understand the mechanism underlying the regression of cardiac hypertrophy, we investigated the pathological changes after isoproterenol (ISO) withdrawal in ISO-induced cardiomyopathy models in rats and neonatal cardiomyocytes. Cardiac hypertrophy was induced in rats by two weeks of ISO administration; however, the hypertrophy did not regress after three weeks of natural maintenance after ISO administration was withdrawn (ISO-wdr group). The remaining hypertrophy in the ISO-wdr group was accompanied by a sustained increase in the level of phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII). Additionally, the increased expression levels of histone deacetylase 4 (HDAC4) and the CaV1.2 channel and amounts of CaMKII bound with HDAC4 and CaV1.2 were not recovered in the ISO-wdr group. The results in cardiomyocyte models were similar to those seen in rat models. Losartan, metoprolol or amlodipine neither ameliorated the increase in atrial natriuretic peptide nor inhibited the increase in p-CaMKII and bound CaMKII. In contrast, autocamtide-2-related inhibitor peptide, a CaMKII inhibitor, reduced these increases. This study investigated the phosphorylation status of CaMKII after hypertrophic stimulus was withdrawn for the first time and proposed that CaMKII as well as its complexes with CaV1.2 could be potential targets to achieve effective regression of cardiac hypertrophy.http://www.sciencedirect.com/science/article/pii/S1347861320300657Cardiac hypertrophyRegressionSustainedCalmodulin-dependent protein kinase IICaV1.2 channel |
| spellingShingle | Jingyuan Li Qinghua Gao Siqi Wang Ze Kang Zhuo Li Shuai Lei Xuefei Sun Meimi Zhao Xiye Chen Guangyu Jiao Huiyuan Hu Liying Hao Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats Journal of Pharmacological Sciences Cardiac hypertrophy Regression Sustained Calmodulin-dependent protein kinase II CaV1.2 channel |
| title | Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats |
| title_full | Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats |
| title_fullStr | Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats |
| title_full_unstemmed | Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats |
| title_short | Sustained increased CaMKII phosphorylation is involved in the impaired regression of isoproterenol-induced cardiac hypertrophy in rats |
| title_sort | sustained increased camkii phosphorylation is involved in the impaired regression of isoproterenol induced cardiac hypertrophy in rats |
| topic | Cardiac hypertrophy Regression Sustained Calmodulin-dependent protein kinase II CaV1.2 channel |
| url | http://www.sciencedirect.com/science/article/pii/S1347861320300657 |
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