PMID- 32505836
OWN - NLM
STAT- MEDLINE
DCOM- 20210705
LR  - 20211204
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 159
DP  - 2020 Sep
TI  - Sestrin2 as a potential therapeutic target for cardiovascular diseases.
PG  - 104990
LID - S1043-6618(20)31298-6 [pii]
LID - 10.1016/j.phrs.2020.104990 [doi]
AB  - Sestrin2 is a cysteine sulfinyl reductase that plays crucial roles in regulation 
      of antioxidant actions. Sestrin2 provides cytoprotection against multiple stress 
      conditions, including hypoxia, endoplasmic reticulum (ER) stress and oxidative 
      stress. Recent research reveals that upregulation of Sestrin2 is induced by 
      various transcription factors such as p53 and activator protein 1 (AP-1), which 
      further promotes AMP-activated protein kinase (AMPK) activation and inhibits 
      mammalian target of rapamycin protein kinase (mTOR) signaling. Sestrin2 triggers 
      autophagy activity to reduce cellular reactive oxygen species (ROS) levels by 
      promoting nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) activation 
      and Kelch-like ECH-associated protein 1 (Keap1) degradation, which plays a 
      pivotal role in homeostasis of metabolic regulation. Under hypoxia and ER stress 
      conditions, elevated Sestrin2 expression maintains cellular homeostasis through 
      regulation of antioxidant genes. Sestrin2 is responsible for diminishing cellular 
      ROS accumulation through autophagy via AMPK activation, which displays 
      cardioprotection effect in cardiovascular diseases. In this review, we summarize 
      the recent understanding of molecular structure, biological roles and biochemical 
      functions of Sestrin2, and discuss the roles and mechanisms of Sestrin2 in 
      autophagy, hypoxia and ER stress. Understanding the precise functions and exact 
      mechanism of Sestrin2 in cellular homeostasis will provide the evidence for 
      future experimental research and aid in the development of novel therapeutic 
      strategies for cardiovascular diseases.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Gao, Anbo
AU  - Gao A
AD  - Institute of Pharmacy and Pharmacology, Hengyang Medical School, University of 
      South China, Hengyang 421002, Hunan, People's Republic of China; Hunan Province 
      Cooperative Innovation Center for Molecular Target New Drug Study, University of 
      South China, Hengyang 421002, Hunan, People's Republic of China.
FAU - Li, Feng
AU  - Li F
AD  - Medical Shcool, Hunan University of Chinese Medicine, Changsha 410000, Hunan, 
      People's Republic of China.
FAU - Zhou, Qun
AU  - Zhou Q
AD  - Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery 
      System, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 
      418000, Hunan, People's Republic of China. Electronic address: 51281656@qq.com.
FAU - Chen, Linxi
AU  - Chen L
AD  - Institute of Pharmacy and Pharmacology, Hengyang Medical School, University of 
      South China, Hengyang 421002, Hunan, People's Republic of China; Hunan Province 
      Cooperative Innovation Center for Molecular Target New Drug Study, University of 
      South China, Hengyang 421002, Hunan, People's Republic of China; Hunan Provincial 
      Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan 
      Provincial Science and Technology Department, 28 Western Changshen Road, Hengyang 
      421002, Hunan, People's Republic of China. Electronic address: lxchen6@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200604
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Cardiovascular Agents)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nuclear Proteins)
RN  - 0 (SESN2 protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - *Autophagy/drug effects
MH  - Cardiovascular Agents/therapeutic use
MH  - Cardiovascular Diseases/drug therapy/*enzymology/pathology
MH  - Cardiovascular System/drug effects/*enzymology/pathology
MH  - Cell Hypoxia
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - NF-E2-Related Factor 2/metabolism
MH  - Nuclear Proteins/drug effects/*metabolism
MH  - Oxidative Stress
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Cardiovascular diseases
OT  - Endoplasmic reticulum stress
OT  - Oxidative stress
OT  - Sestrin2
EDAT- 2020/06/09 06:00
MHDA- 2021/07/06 06:00
CRDT- 2020/06/08 06:00
PHST- 2020/04/17 00:00 [received]
PHST- 2020/05/17 00:00 [revised]
PHST- 2020/05/31 00:00 [accepted]
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2021/07/06 06:00 [medline]
PHST- 2020/06/08 06:00 [entrez]
AID - S1043-6618(20)31298-6 [pii]
AID - 10.1016/j.phrs.2020.104990 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Sep;159:104990. doi: 10.1016/j.phrs.2020.104990. Epub 2020 
      Jun 4.