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
N1 - Publisher Copyright:
© 2019 World Scientific Publishing Company.
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
UR - http://www.scopus.com/inward/record.url?scp=85062907504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062907504&partnerID=8YFLogxK
U2 - 10.1142/S0192415X19500162
DO - 10.1142/S0192415X19500162
M3 - Article
AN - SCOPUS:85062907504
SN - 0192-415X
VL - 47
SP - 337
EP - 350
JO - American Journal of Chinese Medicine
JF - American Journal of Chinese Medicine
IS - 2
ER -