Sestrin2 overexpression alleviates hydrogen peroxide-induced apoptosis and oxidative stress in retinal ganglion cells by enhancing Nrf2 activation via Keap1 downregulation

Fan, Ya-Zhi; Yao, Xing; Xiong, Lei; Wang, Jianming

doi:10.1016/j.cbi.2020.109086

Cited by 34 publications

(32 citation statements)

References 39 publications

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“…Their study demonstrated that SESN2, as a target gene of P53, could activate the AMP‐responsive protein kinase (AMPK) and inhibit mTOR. Subsequently, studies have confirmed that SESN2 is a stress‐inducible protein that responds to various insults, such as hypoxia, oxidative stress, endoplasmic reticulum (ER) stress and DNA damage 8,12,15 . In addition, SESN2 plays a crucial role in cancer, metabolic disorders, cardiovascular diseases and neurodegenerative disorders 10,13,16,17 …”

Section: General Background Of Sesn2mentioning

confidence: 99%

“…The accumulation of the products of oxidative stress causes ageing, 22 neurodegenerative diseases, 23 cardiovascular diseases, 24 inflammatory response 25 and metabolic syndrome 26 . Recent studies demonstrated that SESN2 plays a crucial role in oxidative stress through the nuclear factor erythroid 2‐related factor 2 (NRF2) pathway 15,27‐29 . The mechanism by which SESN2 activates NRF2 expression was revealed by Bae et al, 30 who showed that the antioxidant function of SESN2 was mediated through activation of NRF2 in a manner reliant on p62‐dependent autophagic degradation of Kelch‐like ECH‐associated protein 1 (KEAP1).…”

Section: Sesn2 and Signalling Pathwaysmentioning

confidence: 99%

“…Fan et al 15 proved that SESN2 overexpression markedly decreased H 2 O 2 ‐induced apoptosis and ROS generation. A study by Ro et al 31 demonstrated that uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT) and generates heat by uncoupling oxidative phosphorylation, can be inhibited by SESN2 via a reduction in ROS accumulation.…”

Section: Sesn2 and Signalling Pathwaysmentioning

confidence: 99%

“…Bae et al 30 suggested the antioxidant activity of SESN2 was mediated by NRF2 activation, which was dependent on p62‐dependent autophagy of KEAP1. Fan et al 15 found that SESN2 played an essential role in retinal degeneration in glaucoma by enhancing NRF2 activation via KEAP1 downregulation. Moreover, obesity‐related nonalcoholic fatty liver disease could be improved via the SESN2/NRF2/haeme oxygenase 1 (HO‐1) pathway 27 .…”

Section: Sesn2 and Signalling Pathwaysmentioning

confidence: 99%

See 3 more Smart Citations

Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia‐related diseases

Pan

Chen²,

Li³

et al. 2021

J Cellular Molecular Medi

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Sestrin2 (SESN2) is a conserved stress‐inducible protein (also known as hypoxia‐inducible gene 95 (HI95)) that is induced under hypoxic conditions. SESN2 represses the production of reactive oxygen species (ROS) and provides cytoprotection against various noxious stimuli, including hypoxia, oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. In recent years, the determination of the regulation and signalling mechanisms of SESN2 has increased our understanding of its role in the hypoxic response. SESN2 has well‐documented roles in hypoxia‐related diseases, making it a potential target for diagnosis and treatment. This review discusses the regulatory mechanisms of SESN2 and highlights the significance of SESN2 as a biomarker and therapeutic target in hypoxia‐related diseases, such as cancer, respiratory‐related diseases, cardiovascular diseases and cerebrovascular diseases.

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Section: General Background Of Sesn2mentioning

confidence: 99%

Section: Sesn2 and Signalling Pathwaysmentioning

confidence: 99%

Section: Sesn2 and Signalling Pathwaysmentioning

confidence: 99%

Section: Sesn2 and Signalling Pathwaysmentioning

confidence: 99%

See 2 more Smart Citations

Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia‐related diseases

Pan

Chen²,

Li³

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Furthermore, Nrf2/ARE was a downstream antioxidant signal contributing to the observed protective effects through miR-148b-3p inhibition, and hence sestrin2 induction, in response to OGD/R injury [117]. In the H 2 O 2 -stimulated retinal ganglion cells (RGCs), sestrin2 overexpression increased the nuclear translocation of Nrf2, thereby upregulating the Nrf2/ARE target genes, including HO-1 and NAD(P)H quinone oxidoreductase-1 [118]. As mentioned above, sestrin2 itself may be a downstream target of Nrf2 [48,49].…”

Section: Potential Roles Of Sestrin2 In Age-related Neurodegenerative Diseases: Focusing On Admentioning

confidence: 99%

Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

et al. 2021

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Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

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HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress

Shi

Zhang

Wang

et al. 2021

Clinical & Translational Med

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BackgroundThe key role of hypoxia‐inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative stress and HIF2α in ccRCC remain unclear. This research attempts to explore the effect of oxidative stress on the cancer‐promoting effect of HIF2α in ccRCC and reveal its mechanism of action.MethodsThe bioinformatics analysis for ccRCC is based on whole transcriptome sequencing and TCGA database. The detection of the expression level of related molecules is realised by western blot and PCR. The expression of Nucleoside diphosphate‐linked moiety X‐type motif 1 (NUDT1) was knocked down by lentiviral infection technology. The functional role of NUDT1 were further investigated by CCK8 assays, transwell assays and cell oxidative stress indicator detection. The exploration of related molecular mechanisms is realised by Luciferase assays and Chromatin immunoprecipitation (ChIP) assays.ResultsMolecular screening based on knockdown HIF2α sequencing data and oxidative stress related data sets showed that NUDT1 is considered to be an important molecule for the interaction of HIF2α with oxidative stress. Subsequent experimental results showed that NUDT1 can cooperate with HIF2α to promote the progression of ccRCC. And this biological effect was found to be caused by the oxidative stress regulated by NUDT1. Mechanistically, HIF2α transcription activates the expression of NUDT1, thereby inhibiting oxidative stress and promoting the progression of ccRCC.ConclusionsThis research clarified a novel mechanism by which HIF2α stabilises sirtuin 3 (SIRT3) through direct transcriptional activation of NUDT1, thereby inhibiting oxidative stress to promote the development of ccRCC. It provided the possibility for the selection of new therapeutic targets for ccRCC and the study of combination medication regimens.

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Sestrin2 overexpression alleviates hydrogen peroxide-induced apoptosis and oxidative stress in retinal ganglion cells by enhancing Nrf2 activation via Keap1 downregulation

Cited by 34 publications

References 39 publications

Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia‐related diseases

Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia‐related diseases

Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress

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