Cafestol Activates Nuclear Factor Erythroid-2 Related Factor 2 and Inhibits Urotensin II-Induced Cardiomyocyte Hypertrophy

Wen Rui Hao, Li Chin Sung, Chun Chao Chen, Hong Jye Hong, Ju Chi Liu, Jin Jer Chen

研究成果: 雜誌貢獻文章

摘要

Through population-based studies, associations have been found between coffee drinking and numerous health benefits, including a reduced risk of cardiovascular disease. Active ingredients in coffee have therefore received considerable attention from researchers. A wide variety of effects have been attributed to cafestol, one of the major compounds in coffee beans. Because cardiac hypertrophy is an independent risk factor for cardiovascular events, this study examined whether cafestol inhibits urotensin II (U-II)-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed only to U-II (1nM) or to U-II (1nM) following 12-h pretreatment with cafestol (1-10μM). Cafestol (3-10μM) pretreatment significantly inhibited U-II-induced cardiomyocyte hypertrophy with an accompanying decrease in U-II-induced reactive oxygen species (ROS) production. Cafestol also inhibited U-II-induced phosphorylation of redox-sensitive extracellular signal-regulated kinase (ERK) and epidermal growth factor receptor transactivation. In addition, cafestol pretreatment increased Src homology region 2 domains-containing phosphatase-2 (SHP-2) activity, suggesting that cafestol prevents ROS-induced SHP-2 inactivation. Moreover, nuclear factor erythroid-2-related factor 2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression were enhanced by cafestol. Addition of brusatol (a specific inhibitor of Nrf2) or Nrf2 siRNA significantly attenuated cafestol-mediated inhibitory effects on U-II-stimulated ROS production and cardiomyocyte hypertrophy. In summary, our data indicate that cafestol prevented U-II-induced cardiomycyte hypertrophy through Nrf2/HO-1 activation and inhibition of redox signaling, resulting in cardioprotective effects. These novel findings suggest that cafestol could be applied in pharmacological therapy for cardiac diseases.
原文英語
頁(從 - 到)337-350
頁數14
期刊American Journal of Chinese Medicine
47
發行號2
DOIs
出版狀態已發佈 - 一月 1 2019

指紋

Cardiac Myocytes
Hypertrophy
Coffee
Reactive Oxygen Species
Heme Oxygenase-1
Oxidation-Reduction
urotensin II
cafestol
SH2 Domain-Containing Protein Tyrosine Phosphatases
src Homology Domains
Extracellular Signal-Regulated MAP Kinases
Cardiomegaly
Insurance Benefits
Epidermal Growth Factor Receptor
Small Interfering RNA
Transcriptional Activation
Drinking
Heart Diseases
Cardiovascular Diseases
Phosphorylation

ASJC Scopus subject areas

  • Complementary and alternative medicine

引用此文

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title = "Cafestol Activates Nuclear Factor Erythroid-2 Related Factor 2 and Inhibits Urotensin II-Induced Cardiomyocyte Hypertrophy",
abstract = "Through population-based studies, associations have been found between coffee drinking and numerous health benefits, including a reduced risk of cardiovascular disease. Active ingredients in coffee have therefore received considerable attention from researchers. A wide variety of effects have been attributed to cafestol, one of the major compounds in coffee beans. Because cardiac hypertrophy is an independent risk factor for cardiovascular events, this study examined whether cafestol inhibits urotensin II (U-II)-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed only to U-II (1nM) or to U-II (1nM) following 12-h pretreatment with cafestol (1-10μM). Cafestol (3-10μM) pretreatment significantly inhibited U-II-induced cardiomyocyte hypertrophy with an accompanying decrease in U-II-induced reactive oxygen species (ROS) production. Cafestol also inhibited U-II-induced phosphorylation of redox-sensitive extracellular signal-regulated kinase (ERK) and epidermal growth factor receptor transactivation. In addition, cafestol pretreatment increased Src homology region 2 domains-containing phosphatase-2 (SHP-2) activity, suggesting that cafestol prevents ROS-induced SHP-2 inactivation. Moreover, nuclear factor erythroid-2-related factor 2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression were enhanced by cafestol. Addition of brusatol (a specific inhibitor of Nrf2) or Nrf2 siRNA significantly attenuated cafestol-mediated inhibitory effects on U-II-stimulated ROS production and cardiomyocyte hypertrophy. In summary, our data indicate that cafestol prevented U-II-induced cardiomycyte hypertrophy through Nrf2/HO-1 activation and inhibition of redox signaling, resulting in cardioprotective effects. These novel findings suggest that cafestol could be applied in pharmacological therapy for cardiac diseases.",
keywords = "Cafestol, Cardiomyocyte Hypertrophy, Nuclear Factor Erythroid-2 Related Factor 2, Reactive Oxygen Species, Urotensin II",
author = "Hao, {Wen Rui} and Sung, {Li Chin} and Chen, {Chun Chao} and Hong, {Hong Jye} and Liu, {Ju Chi} and Chen, {Jin Jer}",
year = "2019",
month = "1",
day = "1",
doi = "10.1142/S0192415X19500162",
language = "English",
volume = "47",
pages = "337--350",
journal = "American Journal of Chinese Medicine",
issn = "0192-415X",
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TY - JOUR

T1 - Cafestol Activates Nuclear Factor Erythroid-2 Related Factor 2 and Inhibits Urotensin II-Induced Cardiomyocyte Hypertrophy

AU - Hao, Wen Rui

AU - Sung, Li Chin

AU - Chen, Chun Chao

AU - Hong, Hong Jye

AU - Liu, Ju Chi

AU - Chen, Jin Jer

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Through population-based studies, associations have been found between coffee drinking and numerous health benefits, including a reduced risk of cardiovascular disease. Active ingredients in coffee have therefore received considerable attention from researchers. A wide variety of effects have been attributed to cafestol, one of the major compounds in coffee beans. Because cardiac hypertrophy is an independent risk factor for cardiovascular events, this study examined whether cafestol inhibits urotensin II (U-II)-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed only to U-II (1nM) or to U-II (1nM) following 12-h pretreatment with cafestol (1-10μM). Cafestol (3-10μM) pretreatment significantly inhibited U-II-induced cardiomyocyte hypertrophy with an accompanying decrease in U-II-induced reactive oxygen species (ROS) production. Cafestol also inhibited U-II-induced phosphorylation of redox-sensitive extracellular signal-regulated kinase (ERK) and epidermal growth factor receptor transactivation. In addition, cafestol pretreatment increased Src homology region 2 domains-containing phosphatase-2 (SHP-2) activity, suggesting that cafestol prevents ROS-induced SHP-2 inactivation. Moreover, nuclear factor erythroid-2-related factor 2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression were enhanced by cafestol. Addition of brusatol (a specific inhibitor of Nrf2) or Nrf2 siRNA significantly attenuated cafestol-mediated inhibitory effects on U-II-stimulated ROS production and cardiomyocyte hypertrophy. In summary, our data indicate that cafestol prevented U-II-induced cardiomycyte hypertrophy through Nrf2/HO-1 activation and inhibition of redox signaling, resulting in cardioprotective effects. These novel findings suggest that cafestol could be applied in pharmacological therapy for cardiac diseases.

AB - Through population-based studies, associations have been found between coffee drinking and numerous health benefits, including a reduced risk of cardiovascular disease. Active ingredients in coffee have therefore received considerable attention from researchers. A wide variety of effects have been attributed to cafestol, one of the major compounds in coffee beans. Because cardiac hypertrophy is an independent risk factor for cardiovascular events, this study examined whether cafestol inhibits urotensin II (U-II)-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed only to U-II (1nM) or to U-II (1nM) following 12-h pretreatment with cafestol (1-10μM). Cafestol (3-10μM) pretreatment significantly inhibited U-II-induced cardiomyocyte hypertrophy with an accompanying decrease in U-II-induced reactive oxygen species (ROS) production. Cafestol also inhibited U-II-induced phosphorylation of redox-sensitive extracellular signal-regulated kinase (ERK) and epidermal growth factor receptor transactivation. In addition, cafestol pretreatment increased Src homology region 2 domains-containing phosphatase-2 (SHP-2) activity, suggesting that cafestol prevents ROS-induced SHP-2 inactivation. Moreover, nuclear factor erythroid-2-related factor 2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression were enhanced by cafestol. Addition of brusatol (a specific inhibitor of Nrf2) or Nrf2 siRNA significantly attenuated cafestol-mediated inhibitory effects on U-II-stimulated ROS production and cardiomyocyte hypertrophy. In summary, our data indicate that cafestol prevented U-II-induced cardiomycyte hypertrophy through Nrf2/HO-1 activation and inhibition of redox signaling, resulting in cardioprotective effects. These novel findings suggest that cafestol could be applied in pharmacological therapy for cardiac diseases.

KW - Cafestol

KW - Cardiomyocyte Hypertrophy

KW - Nuclear Factor Erythroid-2 Related Factor 2

KW - Reactive Oxygen Species

KW - Urotensin II

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U2 - 10.1142/S0192415X19500162

DO - 10.1142/S0192415X19500162

M3 - Article

AN - SCOPUS:85062907504

VL - 47

SP - 337

EP - 350

JO - American Journal of Chinese Medicine

JF - American Journal of Chinese Medicine

SN - 0192-415X

IS - 2

ER -