Sestrin 1 ameliorates cardiac hypertrophy via autophagy activation.
Cardiac hypertrophy is one of the major risk factors of cardiovascular morbidity and mortality. Autophagy is acknowledged to be an important mechanism regulating cardiac hypertrophy. Sestrin 1, a downstream target gene of p53, has been proven to regulate autophagy. However, the role of Sestrin 1 in cardiac hypertrophy remains unknown. Our study showed that Sestrin 1 mRNA and protein expression declined in pressure overload cardiac hypertrophy and phenylephrine (PE)-induced cardiac hypertrophy. Knockdown of Sestrin 1 by RNAi deteriorated PE-induced cardiac hypertrophy, whereas the overexpression of Sestrin 1 by adenovirus transfection blunted hypertrophy. We discovered that knockdown of Sestrin 1 resulted in impaired autophagy while overexpression of Sestrin 1 resulted in increased autophagy without affecting lysosomal function. In addition, the antihypertrophic effect of Sestrin 1 overexpression was eliminated by autophagy blockade. Importantly, Sestrin 1 targets at the AMPK/mTORC1/autophagy pathway to inhibit cardiac hypertrophy by interaction with AMPK which is responsible for autophagy regulation. Taken together, our data indicate that Sestrin 1 regulates AMPK/mTORC1/autophagy axis to attenuate cardiac hypertrophy.
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Ruicong
R
Xue
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Junyi
J
Zeng
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Yili
Y
Chen
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Cong
C
Chen
Department of Respiratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Weiping
W
Tan
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Jingjing
J
Zhao
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Bin
B
Dong
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Yu
Y
Sun
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Yugang
Y
Dong
Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.|Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.
Chen
C
Liu
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001343:Autophagy / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000235:genetics*; D051379:Mice; D010656:Phenylephrine / Q000633:toxicity; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D000084622:Sestrins
D000091162:AMP-Activated Protein Kinase Kinases; D018797:Cell Cycle Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D010656:Phenylephrine; D011494:Protein Kinases; C531059:Sesn1 protein, mouse; D000084622:Sestrins

AMPK
; Sestrin 1; autophagy; cardiac hypertrophy; phenylephrine