Sestrin2 in hypoxia and hypoxia-related diseases

ABSTRACT

Objectives: Sestrin2 is a stress-inducible protein and play an important role in adapting stress states of cells. This article reviewed the role of Sestrin2 in hypoxia and hypoxia-related diseases to provide new perspectives for future research and new therapeutic targets for hypoxia-related diseases.

Methods: A review was conducted through an electronic search of PubMed and Medline databases. Keywords included Sestrin2, ROS, hypoxia, and hypoxia-related disease. Articles from 2008 to 2021 were mostly included and older ones were not excluded.

Results: Sestrin2 is upregulated under various stress conditions, especially hypoxia. Under hypoxic condition, Sestrin2 plays a protective role by reducing the generation of ROS through various pathways, such as adenosine monophosphatea-ctivated protein kinase (AMPK) / mammalian target of rapamycin (mTOR) pathway and nuclear factor-E2-related factor2 (Nrf2) pathway. In addition, Sestrin2 is involved in various hypoxia-related diseases, such as cerebral hypoxic disease, myocardial hypoxic disease, hypoxia-related respiratory disease, and diabetes.

Discussion: Sestrin2 is involved in various hypoxia-related diseases and maybe a therapeutic target. Furthermore, most studies focus on cerebral and myocardial ischemia reperfusion. More researches on hypoxia-related respiratory diseases, kidney injury, and diabetes are needed in future.

KEYWORDS:

• Sestrin2
• hypoxia
• reactive oxygen species (ROS)
• ischemia/reperfution (I/R)
• cardiomyocyte
• hypoxia-related diseases
• chronic obstructive pulmonary disease (COPD)
• obstructive sleep apnea (OSA)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81560589, 30960450, 81173110, 81402991], the Yunnan Provincial Science and Technology Department [grant numbers 2019FE001 (-058), 202001AY070001-044], Yunnan Provincial Department of Education [grant number 2018JS161].