Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin
Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and expl...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/5609121 |
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| author | Hsu-Lung Jen Po-Len Liu Yung-Hsiang Chen Wei-Hsian Yin Jaw-Wen Chen Shing-Jong Lin |
| author_facet | Hsu-Lung Jen Po-Len Liu Yung-Hsiang Chen Wei-Hsian Yin Jaw-Wen Chen Shing-Jong Lin |
| author_sort | Hsu-Lung Jen |
| collection | DOAJ |
| description | Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy. |
| format | Article |
| id | doaj-art-babf71f95c714a36b91f43e81edac7a3 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-babf71f95c714a36b91f43e81edac7a32025-02-03T01:21:24ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/56091215609121Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and AdiponectinHsu-Lung Jen0Po-Len Liu1Yung-Hsiang Chen2Wei-Hsian Yin3Jaw-Wen Chen4Shing-Jong Lin5Division of Cardiology, Cheng-Hsin General Hospital, Taipei, TaiwanDepartment of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanDivision of Cardiology, Cheng-Hsin General Hospital, Taipei, TaiwanInstitute of Clinical Medicine, Faculty of Medicine, Institute of Pharmacology, and Cardiovascular Research Centre, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, Faculty of Medicine, Institute of Pharmacology, and Cardiovascular Research Centre, National Yang-Ming University, Taipei, TaiwanPeroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.http://dx.doi.org/10.1155/2016/5609121 |
| spellingShingle | Hsu-Lung Jen Po-Len Liu Yung-Hsiang Chen Wei-Hsian Yin Jaw-Wen Chen Shing-Jong Lin Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin Mediators of Inflammation |
| title | Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin |
| title_full | Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin |
| title_fullStr | Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin |
| title_full_unstemmed | Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin |
| title_short | Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin |
| title_sort | peroxisome proliferator activated receptor α reduces endothelin 1 caused cardiomyocyte hypertrophy by inhibiting nuclear factor κb and adiponectin |
| url | http://dx.doi.org/10.1155/2016/5609121 |
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