Role of sestrin2 in the regulation of proinflammatory signaling in macrophages

Yang, Ji Hye; Kim, Kyu Min; Kim, Mi Gwang; Seo, Kyu Hwa; Han, Jae Yoon; Ka, Sun-O; Park, Byung‐Hyun; Shin, Sook; Ku, Sae Kwang; Cho, Il Je; Ki, Sung Hwan

doi:10.1016/j.freeradbiomed.2014.11.002

Cited by 95 publications

(70 citation statements)

References 44 publications

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“…Sesn2 also plays an essential role in protecting cells against various stresses [13]. Accumulated evidence indicates that Sesn2 induction is transcriptionally regulated by the activations of Nrf2 [17], HIF, p53 [14], c-jun [18], and ATF4 [43]. We previously reported antioxidant response element (ARE) is located from -550 to -539 bp in human Sesn2 promoter and that Nrf2 activation regulates Sesn2 expression [17].…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant adenovirus to express murine Sesn2 was generated as previously described [18], and adenovirus expressing green fluorescence protein (Ad-GFP) was used as an infection control. Virus titer was calculated from TCID 50 method.…”

Section: Preparation Of Recombinant Adenovirus and Transductionmentioning

confidence: 99%

“…We previously reported Sesn2 is upregulated by NF-E2-related factor 2 (Nrf2), an essential transcription factor for the induction of antioxidant genes, and that Sesn2 induction protects hepatocytes from oxidative damages [17]. In addition, growing evidence indicates Sesn2 induction might be promising strategy for the treatment of many liver diseases, such as hepatitis [18], metabolic liver diseases [19] and even hepatocellular carcinoma [20].…”

Section: Introductionmentioning

confidence: 99%

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Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Jegal

Park

et al. 2016

Apoptosis

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Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) has many pharmacological activities including anti-inflammation, anti-oxidant and anti-cancer effects. Autophagy is the basic cellular machinery involving the digestion of damaged cellular components. In the present study, we investigated the protection effects of eupatilin against arachidonic acid (AA) and iron-induced oxidative stress in HepG2 cells and tried to elucidate the molecular mechanisms responsible. Eupatilin increased cell viability against AA + iron in a concentration-dependent manner and prevented mitochondrial dysfunction and reactive oxygen species (ROS) production. In addition, AA + iron increased the levels of pro-apoptotic proteins and these changes were prevented by eupatilin. Eupatilin also induced autophagy, as evidenced by the accumulation of microtubule-associated protein 1 light chain3-II and the detection of autophagic vacuoles. Furthermore, the protective effects of eupatilin on mitochondrial dysfunction and ROS production were significantly abolished by autophagy inhibitors. Eupatilin also increased the mRNA level of sestrin-2 and its promoter-driven reporter gene activity, which resulted in the up-regulation of sestrin-2 protein. Finally, gene silencing using sestrin-2 siRNA and the ectopic expression of recombinant adenoviral sestrin-2 indicated that sestrin-2 induction by eupatilin was required for autophagy-mediated cytoprotection against AA + iron. Our results suggest that eupatilin activates sestrin-2-dependent autophagy, thereby preventing oxidative stress induced by AA + iron.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Recombinant Adenovirus and Transductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Jegal

Park

et al. 2016

Apoptosis

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“…Therefore, the function of Sesns in different immune cells including macrophage, T cells has received much attention. In RAW 264.7 cells, a widely used model of mouse macrophages, the expression of Sesn2 was up-regulated upon different stresses, such as hypoxia, nitric oxide, oxidized low-density lipoprotein (oxLDL) and lipopolysaccharide (LPS) [69-73]. The upstream regulators responsible for the Sesn2 expression in macrophages could be different.…”

Section: Sesns In Immune Systemmentioning

confidence: 99%

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

Wang

Liu

et al. 2017

Cell Physiol Biochem

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Sestrins (Sesns) have been identified as a family of highly conserved stress-inducible proteins that are strongly up-regulated by various stresses, including DNA damage, oxidative stress, and hypoxia. The Sesns play protective roles in most physiological and pathological conditions mainly through the regulation of oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and metabolic homeostasis. In this review, we discussed the possible regulators of Sesns expression, such as p53, forkhead box O, nuclear factor erythroid 2 like 2 (Nrf2), NH (2)-terminal kinase (JNK)/c-Jun pathway and hypoxia-inducible factor-1α (Hif-1α), and the downstream pathways regulated by the Sesns including AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, mitogen-activated protein kinases (MAPKs) signaling, Nrf2 signaling, NADPH oxidase signaling and transforming growth factor β (TGF-β) signaling in heart diseases, lung diseases, gastrointestinal tract diseases, liver and metabolism diseases, neurological diseases, kidney diseases and immunological diseases. This review aims to provide a comprehensive understanding the protective effects of Sesns.

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“…Sesn2 expression reduced the serum ALT and AST levels induced by Gal/LPS. 37) Gal/LPS treatment increased the degeneration of hepatocytes and the number of infiltrated inflammatory cells, which were attenuated by Sesn2. In addition, Sesn2 restored depleted GSH content and blocked inflammatory cytokine production (e.g., tumor necrosis factoralpha (TNF-α), interleukin-6 (IL-6), and IL-1β) induced by Gal/LPS.…”

Section: Role Of Sestrin2 As a Regulator Of Redox-homeostasismentioning

confidence: 95%

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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Role of sestrin2 in the regulation of proinflammatory signaling in macrophages

Cited by 95 publications

References 44 publications

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

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

Sestrin2: A Promising Therapeutic Target for Liver Diseases

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