Sestrin2 is an endogenous antioxidant that improves contractile function in the heart during exposure to ischemia and reperfusion stress

Li, Meina; Sun, Meihua; Zhang, Yaoting; Li, Xuan; Sun, Wanqing; Quan, Nanhu

doi:10.1016/j.freeradbiomed.2021.01.048

Cited by 17 publications

(18 citation statements)

References 58 publications

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“…Mitochondria have an important role in ROS degradation, and dysfunctional mitochondria are the main sources of pathological ROS (105,106). AMPK can protect mitochondria and play an antioxidant role during the I/R process (78). Furthermore, AMPK has an essential role in the activation of glucose uptake in the ischemic heart (107)(108)(109).…”

Section: Sestrin2 and Myocardial Ischemia/ Reperfusion Injurymentioning

confidence: 99%

“…Coronary heart disease, also known as ischemic heart disease (IHD), refers to the interruption of blood flow to the heart muscle due to atherosclerosis, coronary thrombosis, and narrowing of the small arteries of the heart, which remains the leading cause of death worldwide because the incidence of IHD increases with age ( 100 , 101 ). After an acute myocardial infarction, although early and successful myocardial reperfusion through thrombolytic or percutaneous coronary intervention is the most effective way to rescue the ischemic heart and improve the clinical outcome, the recovery of blood flow can result in myocardial injury, which reduces the efficacy of myocardial reperfusion, namely ischemia/reperfusion (I/R) injury ( 78 , 102 ). Myocardial I/R injury is closely related to ROS, calcium overload, energy metabolism disorders, acidosis, and inflammation ( 102 ).…”

Section: Role Of Sestrin2 In Diabetes Non-alcoholic Fatty Liver Disease and Myocardial Ischemia/reperfusion (I/r) Injurymentioning

confidence: 99%

“…Sestrin2 protects mitochondrial function by activating the AMPK/PGC-1α signaling pathway during myocardial ischemia ( 73 ). Sestrin2 has been shown to be upregulated under anoxic and ischemic conditions and has a protective role against myocardial ischemia ( 7 , 74 , 78 ). The loss of Sestrin2 aggravates the accumulation of fatty acids, thereby altering substrate metabolism in the heart and increasing the production of ROS ( 37 , 78 ).…”

Section: Role Of Sestrin2 In Diabetes Non-alcoholic Fatty Liver Disease and Myocardial Ischemia/reperfusion (I/r) Injurymentioning

confidence: 99%

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Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

Gong

Wang

et al. 2021

Front. Endocrinol.

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Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolism via a number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.

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Section: Sestrin2 and Myocardial Ischemia/ Reperfusion Injurymentioning

confidence: 99%

Section: Role Of Sestrin2 In Diabetes Non-alcoholic Fatty Liver Disease and Myocardial Ischemia/reperfusion (I/r) Injurymentioning

confidence: 99%

Section: Role Of Sestrin2 In Diabetes Non-alcoholic Fatty Liver Disease and Myocardial Ischemia/reperfusion (I/r) Injurymentioning

confidence: 99%

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Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

Gong

Wang

et al. 2021

Front. Endocrinol.

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“…The expression of Sestrin2 significantly increases during inflammatory response to protect against oxidative stress and confine the progressive organ damage [7,8]. Consistently, Sestrin2 knockout is associated with a burst of oxidative stress, more severe inflammatory response, and exacerbation of disease manifestations [7,8]. Redistribution and increased expression of Sestrin2 act as endogenous defense mechanisms against organ damage [9].…”

Section: Introductionmentioning

confidence: 90%

Target Sestrin2 to Rescue the Damaged Organ: Mechanistic Insight into Its Function

Ala

Eftekhar

2021

Oxidative Medicine and Cellular Longevity

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Sestrin2 is a stress-inducible metabolic regulator and a conserved antioxidant protein which has been implicated in the pathogenesis of several diseases. Sestrin2 can protect against atherosclerosis, heart failure, hypertension, myocardial infarction, stroke, spinal cord injury neurodegeneration, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, acute kidney injury (AKI), chronic kidney disease (CKD), and pulmonary inflammation. Oxidative stress and cellular damage signals can alter the expression of Sestrin2 to compensate for organ damage. Different stress signals such as those mediated by P53, Nrf2/ARE, HIF-1α, NF-κB, JNK/c-Jun, and TGF-β/Smad signaling pathways can induce Sestrin2 expression. Subsequently, Sestrin2 activates Nrf2 and AMPK. Furthermore, Sestrin2 is a major negative regulator of mTORC1. Sestrin2 indirectly regulates the expression of several genes and reprograms intracellular signaling pathways to attenuate oxidative stress and modulate a large number of cellular events such as protein synthesis, cell energy homeostasis, mitochondrial biogenesis, autophagy, mitophagy, endoplasmic reticulum (ER) stress, apoptosis, fibrogenesis, and lipogenesis. Sestrin2 vigorously enhances M2 macrophage polarization, attenuates inflammation, and prevents cell death. These alterations in molecular and cellular levels improve the clinical presentation of several diseases. This review will shed light on the beneficial effects of Sestrin2 on several diseases with an emphasis on underlying pathophysiological effects.

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“…The ROS accumulation and ATP lack are important factors of cardiomyocyte damage. Accordingly, many researchers have explored the antioxidant role of Sestrin2 in the process of myocardial hypoxia [50][51][52].…”

Section: Sestrin2 and Myocardial Hypoxic Diseasementioning

confidence: 99%

Sestrin2 in hypoxia and hypoxia-related diseases

et al. 2021

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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.

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Sestrin2 is an endogenous antioxidant that improves contractile function in the heart during exposure to ischemia and reperfusion stress

Cited by 17 publications

References 58 publications

Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

Target Sestrin2 to Rescue the Damaged Organ: Mechanistic Insight into Its Function

Sestrin2 in hypoxia and hypoxia-related diseases

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