Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway

Gao, Yan; Fu, Rong-Rong; Wang, Jue; Yang, Xue; Wen, Lulu; Feng, Juan

doi:10.1080/13880209.2018.1502326

Cited by 72 publications

(76 citation statements)

References 48 publications

(58 reference statements)

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“…The observed decreases in ROS and MDA upon exposure of HYPX may therefore be due to the increase repair of respiratory chain enzyme complex activity through upregulation of rGSH and GPx redox system in the mitochondria of SH-SY5Y cells. Consistent with these findings, treatment of RSV diminished mitochondrial ROS and www.nature.com/scientificreports www.nature.com/scientificreports/ MDA through upregulation of rGSH and GPx in the brain of neonatal rats with hypoxic-ischemic encephalopathy 41 and the HYPX/reoxygenation-induced H9c2 cardiomyocyte cell line 42 .…”

Section: Discussionsupporting

confidence: 67%

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

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Hypoxia (HYpX) induced-overload ca 2+ entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca 2+ permeable TRPM2 channel was gated by ADPribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 μM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl 2 (200 μM and 24 hours) incubation was used. HYPX-induced intracellular Ca 2+ responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H 2 o 2 and ADPR. RSV treatment improved intracellular ca 2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β and tnf-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn 2+ , apoptosis, cell death, PARP-1, TRPM2 expression, caspase −3 and −9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.Extensive death in neurons was induced by acute hypoxia, because disability and mortality of the neurons were increased by acute hypoxia 1 . Low blood flow to the tissue and low oxygen content of blood result in hypoxia and ischemic condition 2 . Cell survival decreased in the absence of oxygen, because ATP generation requires oxygen consumption in mitochondria 3 . Mitochondria is a main source of reactive oxygen species (ROS) generation 4 . Accumulating evidence indicates that the hypoxia and ischemic conditions result in excessive ROS generation, inflammation and apoptosis through the increase of membrane depolarization in mitochondria of neurons 5,6 . The increase of mitochondrial membrane depolarization was induced by the increase of intracellular free Ca 2+ ([Ca 2+ ] i ) concentration. Recently, hypoxia-induced mitochondria ROS generation was inhibited through modulation of voltage gated calcium channel (VGCC) in the heart cells by resveratrol (RSV) treatment 7,8 . Hence, RSV can be useful for treatment of hypoxia in neuronal cells by modulation of mitochondrial ROS generation and the subject should be clarified in the hypoxia-induced SH-SY5Y neuronal cells.Several neuronal physiological functions such as mitochondria and cell development are triggered by the changes of the [Ca 2+ ] i concentration 4 . In addition, several neurotoxicity functions such as apoptosis and inflammation in hypoxia are...

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Section: Discussionsupporting

confidence: 67%

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

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“…36 Furthermore, resveratrol mitigates hypoxicischemic induced oxidative stress and brain injury in neonatal rats via Nrf2/HO-1 pathway. 37 Presently, to investigate the underlying mechanism of the neuroprotective role of miR-146b-5p in HIE, we conducted bioinformatics analysis and found that IRAK1 was a promising candidate target of miR-146b-5p. Indeed, we found that IRAK1 was upregulated in HIE brain lesions and negatively correlated with the expression of miR-146b-5p.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

Yang

Zhao

2020

Yonsei Med J

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Purpose: Neonatal hypoxic ischemic encephalopathy (HIE) is an essential factor underlying neonatal death and disability. This study sought to explore the role of miR-146b-5p in regulating neonatal HIE. Materials and Methods: In vitro and in vivo HIE models were established in PC12 cells and 10-day neonatal Sprague Dawley rats, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess miR-146b-5p expression and inflammatory factors [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] in brain lesions and PC12 cells, while enzymelinked immunosorbent assay was employed to detect the expression of oxidative stress factors (SOD and GSH-Px). Gain-and loss-assays of miR-146b-5p were conducted to verify its role in modulating the viability and apoptosis of PC12 cells under oxygenglucose deprivation (OGD) treatment. Expression of TLR4, IRAK1, TRAF6, TAK1, and NF-κB were examined by qRT-PCR and/or Western blot. Dual luciferase activity assay was conducted to identify relationships between miR-146b-5p and IRAK1. Results: In the HIE models, significant oxidative stress and inflammatory responses emerged upon upregulation of TLR4/IRAK1/ TRAF6/TAK1/NF-κB signaling. Overexpression of miR-146b-5p greatly inhibited OGD-induced PC12 cell injury, inflammatory responses, and oxidative stress. Inhibiting miR-146b-5p, however, had the opposite effects. IRAK1 was found to be a target of miR-146b-5p, and miR-146b-5p overexpression suppressed the activation of IRAK1/TRAF6/TAK1/NF-κB signaling. Conclusion: This study demonstrated that miR-146b-5p overexpression alleviates HIE-induced neuron injury by inhibiting the IRAK1/TRAF6/TAK1/NF-κB pathway.

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“…Oxygen-glucose deprivation/reoxygenation (OGD/R) is a widely used cell model to mimic the aspects of cell death observed in a hypoxia brain injury model, including neonate HI and adult ischemic stroke (Cengiz et al, 2014; Tasca et al, 2015). Several recent studies demonstrated that Nrf2 was regulated by special compounds in the rat neonatal HI brain injury model (Cui et al, 2017; Gao et al, 2018). We speculated that TTB may offer neuroprotection in part by regulating Nrf2 in reactive astrocytes.…”

Section: Introductionmentioning

confidence: 99%

TTB Protects Astrocytes Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Activation of Nrf2/HO-1 Signaling Pathway

et al. 2019

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Neonatal hypoxic/ischemic encephalopathy (NHIE) is a severe condition that leads to death or neurological disability in newborns. The underlying pathological mechanisms are unclear, and developing the target neuroprotective strategies are urgent. 2,7,2′-trihydroxy-4,4′7′-trimethoxy-1,1′-biphenanthrene (TTB) is a natural product isolated from Cremastra appendiculata (D. Don) Makino and Liparis nervosa (Thunb.) Lindl. TTB has demonstrated potent cytotoxic activity against stomach (HGC-27) and colon (HT-29) cancer cell lines. However, none of the studies have addressed the effects of TTB in NHIE. In the present study, an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced astrocyte injury model was established to investigate the effect of TTB and its potential mechanisms. Our results showed that TTB alleviated the OGD/R-induced reactive oxygen species increase and the intracellular antioxidant capacity of superoxide dismutase activity decrease. Moreover, TTB potentially prolonged the activation state of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and maintained the protection against oxidative stress in OGD/R-induced astrocytes by inducing the nuclear translocation and up-regulation of Nrf2 along with the enhanced expression of the downstream target gene HO-1. Furthermore, TTB treatment diminished the accumulation of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression induced by OGD/R. We also found TTB-treated astrocytes reversed the inhibition of OGD/R on neurite growth of neurons by the astrocyte-neuron coculture system. In conclusion, TTB inhibited the OGD/R-induced astrocyte oxidative stress at least partially through the inhibition of HIF-1α and VEGF via the Nrf2/HO-1 signaling pathway.

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Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway

Cited by 72 publications

References 48 publications

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Overexpression of miR-146b-5p Ameliorates Neonatal Hypoxic Ischemic Encephalopathy by Inhibiting IRAK1/TRAF6/TAK1/NF-αB Signaling

TTB Protects Astrocytes Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Activation of Nrf2/HO-1 Signaling Pathway

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