SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells

Chen, Mengfan; Wang, Zheng; Zhou, Wenying; Lu, Chenxi; Ji, Ting; Yang, Wenwen; Jin, Zhenxiao; Tian, Ye; Lei, Wangrui; Wu, Songdi; Fu, Qi; Wu, Zhen; Wu, Xue; Han, Mengzhen; Fang, Min-Feng; Yang, Yang

doi:10.1016/j.ejphar.2021.174236

Cited by 25 publications

(23 citation statements)

References 39 publications

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“…Resveratrol treatment reversed the levels of anti-apoptotic proteins and reduced the pro-apoptotic factors in the presence of H/R injury ( Gao et al, 2019 ). Moreover, our study found that mangiferin treatment remarkably decreased the cell apoptotic rate and increased the antiapoptosis molecule Bcl2 induced by H/R injury ( Chen et al, 2021 ). In this study, rh-omentin treatment could significantly reduce H/R-induced injury by inhibiting neuroblastoma apoptosis, as evidenced by remarkably decreased the cell apoptotic rate, Bax expression and increased Bcl2 expression.…”

Section: Discussionmentioning

confidence: 84%

Neuroprotective Effects of Omentin-1 Against Cerebral Hypoxia/Reoxygenation Injury via Activating GAS6/Axl Signaling Pathway in Neuroblastoma Cells

Niu

Cheng

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Ischemic stroke is characterized by insufficient blood supply to brain tissue and is associated with increased morbidity and mortality in adults worldwide. Growth arrest-specific protein 6 (GAS6) is a vitamin K-dependent protein and is widely expressed in the central nervous system. The biological functions of GAS6 are mediated by the interaction with TAM (Tyro3, Axl and Mertk) receptors, including cell survival and proliferation, immune regulation and apoptosis. Omentin-1, also known as intelectin-1 (ITLN-1), is a novel adipocytokine that is involved in a variety of biological events, such as insulin resistance, endothelial dysfunction, programmed cell death and metabolic disorders. Our previous study has found that omentin-1 act as a novel regulator of vascular and anti-apoptotic response in cerebral ischemia. However, the specific molecular mechanism of omentin-1’s protective effect on cerebral ischemia-reperfusion injury (IRI) is still unclear. First, the toxicity of recombinant human omentin-1 (rh-omentin) was assessed and a safe concentration was chosen for the next experiments. Then, rh-omentin exerted neuroprotection against hypoxia/reoxygenation (H/R) injury in N2a cells, indicated by increased cell viability, decreased LDH, ROS generation, and cell apoptotic rate. Furthermore, the similar protective effect was observed in omentin-1 overexpression cells constructed by lentivirus transfection. Rh-omentin could also inhibit H/R-induced apoptotic molecules, oxidative stress molecules, and GAS6/Axl signaling molecules which as evidence by increased omentin-1, GAS6, Axl, p-Axl, NQO1, HO-1, Nrf2, Bcl2 and decreased Bax expressions. However, GAS6 siRNA could reverse rh-omentin-induced neuroprotection and the levels of these molecules mentioned above. In conclusion, these findings suggest that omentin-1 treatment exerts neuroprotection against H/R injury partly via activating GAS6/Axl signaling at least. Therefore, these finding may favor omentin-1 a potential neuroprotective drug candidate to alleviate ischemia-reperfusion injury in clinic.

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Section: Discussionmentioning

confidence: 84%

Neuroprotective Effects of Omentin-1 Against Cerebral Hypoxia/Reoxygenation Injury via Activating GAS6/Axl Signaling Pathway in Neuroblastoma Cells

Niu

Cheng

Zhang

et al. 2022

Front. Cell Dev. Biol.

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“…Mechanistically, MAF exerts anti-inflammatory effects by activating the SIRT1 signaling pathway ( 38 , 39 ). Various studies have revealed that SIRT1 is a key component in a number of stress-related pathways, including cell apoptosis, cellular senescence and angiogenesis ( 40 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1 activation can inhibit the cardiac inflammatory response following ischemia-reperfusion ( 44 ). Once activated, SIRT1 can mediate a wide range of downstream signaling pathways, such as AMPK, peroxisome proliferator-activated receptor γ coactivator 1α and endothelial nitric oxide synthase ( 39 , 42 , 45 ). In the present study, the protein expression of SIRT1 and AMPK was increased in a dose-dependent manner after MAF treatment.…”

Section: Discussionmentioning

confidence: 99%

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Chen

Huang

2021

Exp Ther Med

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Lung ischemia-reperfusion injury (LIRI) is one of the complications that can occur after lung transplantation and may lead to morbidity and mortality. Mangiferin (MAF) is a naturally occurring glucosyl xanthone that has been documented to possess anti-inflammatory, immunomodulatory and potent antioxidant effects. The purpose of the present study was to investigate the effect of MAF on LIRI using a hypoxia-reoxygenation (H/R) cell model. In the present study, the viability of lung alveolar epithelial cells (A549) and H/R-A549 were detected by MTT assay. ELISA was used to evaluate the expression levels of IL-6 and IL-1β. TUNEL assay and western blotting were used to evaluate the apoptosis. In addition, H/R-A549 cells were treated with sirtinol, which is known inhibitor of sirtuin 1 (SIRT1) activity, to determine the effects of MAF on proteins associated with the SIRT1/5'AMP-activate protein kinase (AMPK) signaling pathway using western blotting. The results showed that 20 µM MAF exerted a protective effect on A549 cells against H/R mediating no clear cytotoxic effects. In terms of inflammation, MAF reduced IL-6, IL-1β, cyclooxygenase-2 and inducible nitric oxide synthase expression, which was accompanied by activation of the SIRT1/AMPK signaling pathway. In addition, compared with those in the group treated with sirtinol, expression of SIRT1, Bcl-2 and AMPK activity were elevated in MAF-treated H/R-A549 cells, whereas the expression of Bax, cleaved caspase-3 and cleaved caspase-9 was suppressed. TUNEL analysis of H/R-A549 cells treated with MAF in combination with sirtinol revealed that treatment with sirtinol blocked the SIRT1/AMPK signaling pathway and increased the apoptosis rate compared with the MAF group. Taken together, results of the present study revealed that MAF could inhibit lung H/R cell injury through the SIRT1/AMPK signaling pathway.

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“…LDH release in the culture medium was determined using a commercially available kit according to the manufacturer's protocol. The detailed methods were illustrated in our previous study (Chen et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

“…2′,7′‐Dichlorofluorescin diacetate (DCF‐DA) staining was applied to measure the generation of ROS. The detailed illustration was in our previous study (Chen et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

Psoralidin protects against cerebral hypoxia/reoxygenation injury: Role of GAS6/Axl signaling

Lei

Zhao

et al. 2022

Phytotherapy Research

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Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti‐inflammatory, anti‐vitiligo, anti‐bacterial, and anti‐viral effects. Growth arrest‐specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor‐related factor 2 (Nrf‐2), NAD(P)H dehydrogenase quinone‐1 (NQO1), heme oxygenase‐1 (HO‐1), silent information regulator 1 (SIRT1), peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B‐cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR‐induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling.

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SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells

Cited by 25 publications

References 39 publications

Neuroprotective Effects of Omentin-1 Against Cerebral Hypoxia/Reoxygenation Injury via Activating GAS6/Axl Signaling Pathway in Neuroblastoma Cells

Neuroprotective Effects of Omentin-1 Against Cerebral Hypoxia/Reoxygenation Injury via Activating GAS6/Axl Signaling Pathway in Neuroblastoma Cells

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Psoralidin protects against cerebral hypoxia/reoxygenation injury: Role of GAS6/Axl signaling

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