Upregulation of sestrin-2 expression protects against endothelial toxicity of angiotensin II

Liu, Yi; Li, Feng; Yuan, Yu‐He; Dong, Jianting; Zhang, Liting; Xuansheng, Huang; Fei, Li; Jiewen, Li

doi:10.1007/s10565-014-9276-3

Cited by 46 publications

(37 citation statements)

References 32 publications

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“…In human umbilical vein endothelial cells, the expression of Sesn2 was induced after AngII stimulation with a time-dependent and dose-dependent manner. Also, knockdown of Sesn2 using small RNA interference promoted cellular toxicity of AngII, as demonstrated by the reduced cell viability, exacerbated oxidative stress, and increased apoptosis [21]. …”

Section: Sesns In Heartmentioning

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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Section: Sesns In Heartmentioning

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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“…In hypoxic-ischemic encephalopathy, Sestrin 2 has been shown to reverse neurological dysfunction and provide a neuroprotective effect [18]. Additional evidence has indicated that Sestrin 2 upregulation protects against angiotensin II-induced endothelial dysfunction [19]. Our results unveiled that administration of Sestrin 2 ameliorates liver fibrosis in vivo.…”

Section: Discussionmentioning

confidence: 55%

Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl₄), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl₄ model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway.

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“…Fhit (fragile histidine triad gene transcript) whose protein promotes apoptosis and suppresses cell proliferation (Huang et al , 2014); and 4. Ace (angiotensin converting enzyme transcript), an enzyme which converts angiotensin I to the physiologic active peptide angiotensin II, a proapoptotic protein (Wang et al , 2015, Yi et al , 2014). Two other transcripts downregulated were Ermn whose protein is an oligodendrocyte-specific protein surrounding myelin axons necessary for action potentials (Brockschnieder et al , 2006) and Nrgn involved in promoting synaptic transmission (Zhong et al , 2009).…”

Section: Discussionmentioning

confidence: 99%

Molecular Changes in the Nasal Cavity after N, N-dimethyl-p-toluidine Exposure

et al. 2016

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N,N-Dimethyl-p-toluidine (DMPT) (Cas No. 99-97-8), an accelerant for methyl methacrylate monomers in medical devices, is a nasal cavity carcinogen in a 2-year cancer study in male and female F344/N rats, with the nasal tumors arising from the transitional cell epithelium. In this study we exposed male F344/N rats for five days to DMPT (0, 1, 6, 20, 60 or 120 mg/kg (oral gavage)) to explore early changes in the nasal cavity after short-term exposure. Lesions occurred in the nasal cavity including hyperplasia of transitional cell epithelium (60 and 120 mg/kg). Nasal tissue was rapidly removed and preserved for subsequent laser capture microdissection and isolation of the transitional cell epithelium (0 and 120 mg/kg) for transcriptomic studies. DMPT transitional cell epithelium gene transcript patterns were characteristic of an anti-oxidative damage response (e.g. Akr7a3, Maff, Mgst3), cell proliferation, and decrease in signals for apoptosis. Amino acid transporters transcripts were upregulated (e. g, Slc7a11). The DMPT nasal transcript expression pattern was similar to that found in the rat nasal cavity after formaldehyde exposure with over 1000 transcripts in common. Molecular changes in the nasal cavity after DMPT exposure suggest that oxidative damage is a mechanism for the DMPT toxic and/or carcinogenic effects.

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Upregulation of sestrin-2 expression protects against endothelial toxicity of angiotensin II

Cited by 46 publications

References 32 publications

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

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

Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

Molecular Changes in the Nasal Cavity after N, N-dimethyl-p-toluidine Exposure

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