Role of sestrin2 in H 2 O 2 -induced PC12 apoptosis

Liu, Aiqun; Yu, Qingyun; Xiao, Shifu; Peng, Zhongxing; Huang, Yeqing; Diao, Sheng-Peng; Cheng, Jing; Hong, Ming‐Fan

doi:10.1016/j.neulet.2016.10.043

Cited by 6 publications

(4 citation statements)

References 29 publications

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“…We searched for a possible mechanism of how SESN2 is induced upon hemin challenge. Previous reports showed that SESN2 was highly upregulated by H 2 O 2 in different cell lines (Liu et al, 2017;Ishihara et al, 2013). Consistently, we found here that SESN2 was dosedependently upregulated by H 2 O 2 in both HCT116 and RKO CRC cells (Fig.…”

Section: Hemin-induced Sesn2 Is Dependent On Oxidative Stress and Nrf2 In Crc Cellssupporting

confidence: 92%

The interaction of Hemin and Sestrin2 modulates oxidative stress and colon tumor growth

Kim

Yin

Falcon

et al. 2019

Toxicology and Applied Pharmacology

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Several large epidemiological and animal studies demonstrate a direct correlation between dietary heme iron intake and/or systemic iron levels and cancer risk in several cancers including colorectal cancer (CRC). However, the precise mechanisms for how heme iron contributes to CRC and how cancer cells respond to heme iron-induced stress are still unclear. Previously we have shown that one of the stress-inducible proteins, Sestrin2 (SESN2), is a novel tumor suppressor in colon by limiting endoplasmic reticulum stress and mammalian target of rapamycin complex 1 (mTORC1) signaling and tumor growth. But the relationship between heme iron and SESN2, especially in the context of colon carcinogenesis, was not investigated previously. Here, we found that hemin dosedependently increased SESN2 expression in an oxidative stress and nuclear factor (erythroidderived 2)-like 2 (NFE2L2, NRF2)-dependent manner. Since SESN2 overexpression reduced hemin-induced oxidative stress, SESN2 could be an important target of NRF2 exerting antioxidant function. Indeed, expression of several oxidative stress responsive proteins such as NRF2 and its target genes was reduced by SESN2. Although we formerly reported that SESN2 expression was reduced after p53 mutation in colon tumors, mouse colon tumors, which have intact p53 and NRF2, induced SESN2 expression in response to iron stimulus. Although SESN2 overexpression decreased murine colon tumor cell growth both in vitro and in vivo, it rendered colon cancer cells more resistant to hemin-induced apoptosis and therefore promoted tumor growth during hemin treatment. Taken together, although SESN2 generally suppresses tumorigenesis, it can produce tumor-promoting role in iron-rich environment by suppressing oxidative stress-associated cancer cell death.

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Section: Hemin-induced Sesn2 Is Dependent On Oxidative Stress and Nrf2 In Crc Cellssupporting

confidence: 92%

The interaction of Hemin and Sestrin2 modulates oxidative stress and colon tumor growth

Kim

Yin

Falcon

et al. 2019

Toxicology and Applied Pharmacology

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“…The increased ROS levels and increased expression of activating transcription factor 3 may contribute to the exacerbated neuropathic pain behavior in Sesn2 –/– mice [52]. In PC12 cells, a widely used neuron-like cell model for studying neurotoxicity and neuroprotection, researchers found that the expression of Sesn2 was induced by H 2 O 2 in a time-dependent and dose-dependent manner through the c-Jun NH (2)-terminal kinase (JNK)/c-Jun pathway [53]. The H 2 O 2 induced apoptosis of PC12 cells was further aggravated after Sesn2 knockdown.…”

Section: Sesns In the Nervous 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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“…For example, under oxidative stress, knockdown of SESN2 promoted cell apoptosis in neurological diseases. 33 It was also found that SESN2 protected dendritic cells from endoplasmic reticulum stress-related apoptosis. 34 Moreover, Hanus J, et al found that SESN2 activated by gossypol acetic acid could prevent H 2 O 2 -induced apoptosis of retinal pigment epithelial cells.…”

Section: Discussionmentioning

confidence: 97%

Sestrin 2 protects human lens epithelial cells from oxidative stress and apoptosis induced by hydrogen peroxide by regulating the mTOR/Nrf2 pathway

Tian,

Wei

2024

Int J Immunopathol Pharmacol

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Objective We aimed to explore the effect and potential mechanism of Sestrin 2 (SESN2) in human lens epithelial cells (HLECs). Methods To mimic the oxidative stress environment, SAR01/04 cells were treated with 200 μM hydrogen peroxide (H2O2) for 24 h. Cell viability and apoptosis were checked by cell counting kit-8 and flow cytometry. Western blot was taken to check the protein changes of SESN2, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, ribosomal protein S6 kinase B1 (p70S6K), p-p70S6K, and nuclear factor erythroid 2-related factor 2 (Nrf2). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected via the corresponding reagent kit. The levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay. Results SESN2 was down-regulated in cataract lens tissue and up-regulated in SAR01/04 cells treated with H2O2. Under treatment of H2O2, up-regulation of SESN2 improved cell viability, enhanced the activity of SOD and CAT, inhibited cell apoptosis, and reduced the levels of MDA, ROS, IL-1β, IL-18, and TNF-α, while down-regulation of SESN2 caused the contrary effects. Further bioinformatics analysis suggested that SESN2 regulated the mTOR signaling pathway. Treatment of H2O2 inhibited p-mTOR and p-p70S6K protein expression, while overexpression of SESN2 increased p-mTOR and p-p70S6K protein expression in the H2O2 group and down-regulation of SESN2 further decreased p-mTOR and p-p70S6K protein expression in the H2O2 group. Additionally, H2O2 increased Nrf2 protein expression, and overexpression of SESN2 further increased Nrf2 protein expression in the H2O2 group. Importantly, rapamycin (an inhibitor of mTOR signaling pathway) and knockdown of Nrf2 reversed the promotive effects of SESN2 on cell viability and the inhibitive effects of SESN2 on cell apoptosis, oxidative stress, and inflammatory reaction. Conclusion SESN2 protected HLECs damage induced by H2O2, which was related to the activation of mTOR/Nrf2 pathway.

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Role of sestrin2 in H 2 O 2 -induced PC12 apoptosis

Cited by 6 publications

References 29 publications

The interaction of Hemin and Sestrin2 modulates oxidative stress and colon tumor growth

The interaction of Hemin and Sestrin2 modulates oxidative stress and colon tumor growth

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

Sestrin 2 protects human lens epithelial cells from oxidative stress and apoptosis induced by hydrogen peroxide by regulating the mTOR/Nrf2 pathway

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