Nrf2-ARE pathway regulates induction of Sestrin-2 expression

Shin, Bo Yeon; Jin, Sung-Chul; Cho, Il Je; Ki, Sung Hwan

doi:10.1016/j.freeradbiomed.2012.06.026

Cited by 185 publications

(140 citation statements)

References 30 publications

(42 reference statements)

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“…23) Cells were seeded in 12-well plates and incubated overnight. Serum was removed for 6 h and transient transfection with the luciferase construct and pRL-TK plasmid (a plasmid that encodes for Renilla luciferase and is used to normalize transfection efficacy) was conducted for 3 h using Lipofectamine (Invitrogen, San Diego, CA, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

“…23) Recently, it has been reported as an upstream regulator of AMPK in response to various stresses. 2,28) Given that compound C inhibits AMPK activity and also affects Nrf2-ARE signaling, 9) the effects of compound C on SESN2 expression were tested in HepG2 cells.…”

Section: Compound C-induced Sesn2 Expression In Hepg2mentioning

confidence: 99%

“…19,21) ROS are important stimuli necessary to induce SESN2. 22,23) Recently, Shin et al directly showed that SESN2 protects cells from hydrogen peroxide-induced oxidative stress. 23) Beyond its antioxidant activity, SESN2 influences cell growth by inhibition of mammalian target of rapamycin (mTOR) activity, a kinase complex that regulates protein synthesis.…”

mentioning

confidence: 99%

“…22,23) Recently, Shin et al directly showed that SESN2 protects cells from hydrogen peroxide-induced oxidative stress. 23) Beyond its antioxidant activity, SESN2 influences cell growth by inhibition of mammalian target of rapamycin (mTOR) activity, a kinase complex that regulates protein synthesis. 24) Moreover, SESN2-mediated AMPK signaling protects glucose-depleted cells by mTOR inhibition.…”

mentioning

confidence: 99%

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Compound C Increases Sestrin2 Expression <i>via</i> Mitochondria-Dependent ROS Production

Seo

et al. 2016

Biological & Pharmaceutical Bulletin

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Compound C is a widely used chemical inhibitor that down-regulates AMP-activated protein kinase (AMPK) activity. However, it has been suggested that compound C exerts AMPK-independent effects in various cells. Here, we investigated whether compound C induces Sestrin2 (SESN2), an antioxidant enzyme induced by diverse stress. In addition, the mechanism responsible for SESN2 induction by compound C was determined. Our results showed that compound C increased SESN2 protein expression in HepG2 cells in a concentration-and time-dependent manner. The induction of SESN2 mRNA was also observed in cells treated with compound C. Increase of SESN2 luciferase activity confirmed transcriptional regulation by compound C and this substance also increased nuclear factor erythroid 2 (NF-E2)-related factor-2 (Nrf2) phosphorylation, which implies that Nrf2 was involved in SESN2 induction. Next, we sought to demonstrate whether production of reactive oxygen species (ROS) accompanied SESN2 expression. Compound C increased ROS production, but this effect was prevented by pretreatment with antioxidants or the mitochondrial complex I inhibitor. Moreover, cyclosporin A, an inhibitor of pore formation in the mitochondrial membrane, attenuated compound C-induced SESN2 induction. However, overexpression of a constitutively active form of AMPK was not able to abolish SESN2 induction by compound C, which implies that its action is independent of AMPK inhibition. In conclusion, this is the first study demonstrating that compound C alters mitochondrial function and induces ROS production, which ultimately leads to phosphorylation of Nrf2 and induction of SESN2.

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Section: Methodsmentioning

confidence: 99%

Section: Compound C-induced Sesn2 Expression In Hepg2mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Compound C Increases Sestrin2 Expression <i>via</i> Mitochondria-Dependent ROS Production

Seo

et al. 2016

Biological & Pharmaceutical Bulletin

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“…21,22) Previously, we reported that Nrf2 pathway regulates Sesn2 gene induction. 23,24) Moreover, Sesn2 small interfering RNA (siRNA) abolished the cytoprotective effect of the Nrf2 activator against H 2 O 2 . Inversely, it is also feasible that Sesn2 regulates the Nrf2 pathway.…”

Section: )mentioning

confidence: 99%

Sestrin2: A Promising Therapeutic Target for Liver Diseases

Kim

Yang

Shin

et al. 2015

Biological & Pharmaceutical Bulletin

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Sestrin2 (Sesn2), a highly conserved antioxidant protein, is induced by various stresses, including oxidative and energetic stress, and protects cells against those stresses. In normal physiological conditions, redoxhomeostasis plays an essential role in cell survival and performs the cellular functions to protect the cells against oxidative damage. The liver is susceptible to oxidative stress, since it is responsible for xenobiotic detoxification and energy metabolism. For this reason, oxidative stress is associated with the pathogenesis of liver diseases. Recently, the role of Sesn2 has been investigated in liver injury and related diseases. In this paper, we review the role of Sesn2 in the pathophysiology of liver diseases and the potential clinical applications of Sesn2 as a therapeutic target to prevent/treat liver diseases. This article promotes our understanding of liver disease progression and advances the development of strategies for pharmacological intervention.

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