Recent Insights into the Biological Functions of Sestrins in Health and Disease

Wang, Menglong; Xu, Yao; Liu, Jianfang; Ye, Jing; Yuan, Wancheng; Jiang, Huimin; Wang, Zhen; Jiang, Hong; Wan, Jun

doi:10.1159/000484060

Cited by 61 publications

(46 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMPK induces autophagy in response to different cellular stresses, including oxidative stress [5][6][7][8]. Although the molecular mechanism underlying how ROS modulates AMPK has not been fully established, a role for the sestrin (SESN) family has been proposed [9]. SESN2 belongs to the family of highly conserved antioxidant proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Although it does not possess intrinsic catalytic antioxidant activity, SESN2 plays an important role in suppressing ROS [10]. As a family of stress-inducible proteins, SESNs have been reported to be up-regulated and activated upon exposure to DNA damage, oxidative stress, and hypoxia [9]. There are three isoforms, including Sestrin1 (Sesn1), Sestrin2 (Sesn2), and Sestrin3 (Sesn3).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice

et al. 2019

View full text Add to dashboard Cite

2019) Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice, ABSTRACT Many pathological conditions linked to cigarette smoking are caused by the production of reactive oxygen species (ROS). The present study was conducted to analyze the effect of ROS on the lungs of Swiss mice exposed to cigarette smoking, focusing on autophagy-mediated mechanisms, and investigate the involvement of SESN2, AMPK, and mTOR signaling. Mice were exposed to cigarette smoke (CS) for 7, 15, 30, 45, and 60 days; the control group was not exposed to CS. Only mice exposed to CS for 45 days were selected for subsequent N-acetylcysteine (NAC) supplementation and smoke cessation analyses. Exposure to CS increased the production of ROS and induced molecular changes in the autophagy pathway, including an increase in phosphorylated AMPK and ULK1, reduction in phosphorylated mTOR, and increases in SESN2, ATG12, and LC3B levels. NAC supplementation reduced ROS levels and reversed all molecular changes observed upon CS treatment, suggesting the involvement of oxidative stress in inducing autophagy upon CS exposure. When exposure to CS was stopped, there were decreases in the levels of oxidative stress, AMPK and ULK1 phosphorylation, and autophagy-initiating molecules and increase in mTOR phosphorylation. In conclusion, these results suggest the involvement of ROS, SESN2, AMPK, and mTOR in the CS-induced autophagic process in the lung.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…They validated this candidate in multiple animal models, demonstrating its role as a proconvulsive gene. Prior work showed that SESN3 is a regulator of the intracellular response to reactive oxygen species 15,16 and therefore is not a "classical" epilepsy gene producing an intrinsic effect on membrane excitability, such as an ion channel or neurotransmitter receptor. This work adds to the growing literature showing how deeply intertwined signaling cascades are within neural tissue, and that this interconnectedness provides novel opportunities to intervene to block seizures and comorbidities outside of traditional efforts to target channels and receptors.…”

Section: Key Pointsmentioning

confidence: 99%

2017 WONOEP appraisal: Studying epilepsy as a network disease using systems biology approaches

et al. 2019

View full text Add to dashboard Cite

The revolution in high‐throughput omics technologies has dramatically expanded our understanding of the epilepsies as complex diseases. It is now clear that further progress in treating the full spectrum of seizure disorders requires a systems‐level framework for analyzing and integrating data from multiple omics technologies that moves beyond the search for single molecular alterations to an understanding of dysregulated pathways in epilepsy. Taking such a pathway‐centered view requires further integrating the tools of systems biology into epilepsy research. In this appraisal, we highlight and summarize systems biology approaches in basic epilepsy studies as they were discussed during the 2017 Workshop on the Neurobiology of Epilepsy (WONOEP). During the 3‐day event, participants exchanged emerging results and thoughts on developing the systems biology of epilepsy, and the promise and limitations of these approaches for the near term.

show abstract

“…For example, the paradoxical trend towards increase in glycogen content after IH, despite inhibition of AKT/GSK-3β, may implicate hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1 [33]. Third, in addition to JNK, changes in other stress/hypoxia-inducible pathways including Sestrins, oxidative stress, as well as microRNA profiles should be considered in interpreting the metabolic consequences of IH in liver cells [34][35][36].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

Gu¹,

Yi²,

Feng³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH) on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH₂-terminal-kinase (JNK) contributed to metabolic responses to IH in liver cells. Methods: The human HepG₂ cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O₂ for 60 s followed by 21% O₂ for 60s, 7.5 cycles per hour) or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. Results: IH decreased insulin-stimulated protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1) expression and phosphoenolpyruvate carboxykinase (PEPCK) transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3β phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. Conclusion: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3β phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.

show abstract

Recent Insights into the Biological Functions of Sestrins in Health and Disease

Cited by 61 publications

References 75 publications

Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice

Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice

2017 WONOEP appraisal: Studying epilepsy as a network disease using systems biology approaches

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

Contact Info

Product

Resources

About