Homer1a Attenuates Hydrogen Peroxide-Induced Oxidative Damage in HT-22 Cells through AMPK-Dependent Autophagy

Wu, Xiuquan; Luo, Peng; Rao, Wei; Dai, Shuhui; Zhang, Lei; Ma, Wenke; Pu, Jingnan; Yu, Yang; Wang, Jiu; Zhou, Fei

doi:10.3389/fnins.2018.00051

Cited by 15 publications

(14 citation statements)

References 24 publications

(33 reference statements)

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“…We therefore made an assumption that TLB controls mtROS homeostasis via activating the AMPK-PGC-1α- Sirt3 axis. As expected, the results indicated that H 2 O 2 decreased p-AMPK, in keeping with the theory that oxidative stress acts as a trigger for AMPK (Wu et al, 2018 ). Whereas, TLB promoted AMPK phosphorylation, thereby triggered activation of PGC-1α and ERRα, suggesting that AMPK-PGC-1α-Sirt3 axis was necessary for the protective effect of TLB on regulation of mtROS homeostasis in neuronal cells.…”

Section: Discussionsupporting

confidence: 90%

Trilobatin Protects Against Oxidative Injury in Neuronal PC12 Cells Through Regulating Mitochondrial ROS Homeostasis Mediated by AMPK/Nrf2/Sirt3 Signaling Pathway

Gao

Liu

et al. 2018

Front. Mol. Neurosci.

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Oxidative stress-induced neuronal cell damage is a crucial factor in the pathogenesis of mitochondria-associated neurological diseases. Therefore, elimination of overproduction of mitochondrial reactive oxygen species (mtROS) may be a potential strategy for prevention and treatment of neurological diseases. In the present study, the neuroprotective effects of trilobatin (TLB), a novel small molecule monomer derived from Lithocarpus polystachyus Rehd, and its underlying mechanisms were investigated in vitro using hydrogen peroxide (H2O2)-induced oxidative stress model in a neuron-like PC12 cell. The findings revealed that pre-treatment with TLB dramatically concentration-dependently suppressed H2O2-induced PC12 cells damage by enhancing cell viability, repressed reduction of mitochondrial membrane potential (MMP) and decreased mtROS overgeneration, thereby deferring cell apoptosis. Further study demonstrated that TLB not only increased the enzymatic activities of glutathione peroxidase (GPx), isocitrate dehydrogenase 2 (IDH2),superoxide dismutase 2 (SOD2) and deacetylation of SOD2, but also activated silent mating-type information regulation 2 homolog 3 (Sirt3) within the mitochondria and thereby upregulating forkheadboxO3a (FoxO3a), which regulated mitochondrial DNA genes, then led to improving complex I activity and adenosine triphosphate (ATP) synthesis. What’s more, TLB up-regulated p-adenosine monophosphate-activated protein kinase (AMPK) level, the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α), and ERRα. Intriguingly, TLB failed to mitigate H2O2-induced PC12 injury in the presence of the AMPK inhibitor (Compound C), indicating that the beneficial effects of TLB on the regulation of mtROS homeostasis were reliance on AMPK -Sirt3 signaling pathway. Moreover, TLB also facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted antioxidant gene expression in turn, and knockdown of Nrf2 by siRNA dramatically reduced the neuroprotective effects of TLB. Notably, AMPK inhibitor abolished the activation of Nrf2 and Sirt3, whereas, knockdown of Nrf2 blocked the upregulation of Sirt3, but it did not affect p-AMPK level. In conclusion, our findings demonstrate that TLB protects against oxidative injury in neuronal PC12 cells through regulating mtROS homeostasis in the first time, which is, at least partly, mediated through the AMPK/Nrf2/Sirt3 signaling pathway.

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Section: Discussionsupporting

confidence: 90%

Trilobatin Protects Against Oxidative Injury in Neuronal PC12 Cells Through Regulating Mitochondrial ROS Homeostasis Mediated by AMPK/Nrf2/Sirt3 Signaling Pathway

Gao

Liu

et al. 2018

Front. Mol. Neurosci.

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“…However, accumulation of excess ROS is a potent inducer of dysfunction in CNS, which results in oxidative damage and various neurodegenerative disorders. Chronically elevated levels of H 2 O 2 have been implicated in cell viability in multiple neuronal cells [23, 24]. To determine the H 2 O 2 toxicity on neural cells, alamarBlue reagent was used to assess cell viability.…”

Section: Resultsmentioning

confidence: 99%

MAPK Pathway Inhibitors Attenuated Hydrogen Peroxide Induced Damage in Neural Cells

Fan

Wang

Zhang

et al. 2019

BioMed Research International

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Background. Oxidative stress due to reactive oxygen species plays a central role in pathophysiology of neurodegenerative diseases. Inhibition of mitogen-activated protein kinase (MAPK) cascades attenuates the oxidative induced cell stress and behaves as potential neuroprotection agent. Materials and Methods. In this study, we evaluate hydrogen peroxide induced neural cell stress and determine how different MAPK inhibitors restore the cell damage. Results. The results indicated that oxidative stress induced by neural cell damage commonly exists, and MAPK inhibitors partially and selectively attenuated the cell damage by reducing ROS production and cell apoptosis. The cultured neurons are more susceptible to hydrogen peroxide than subculture cells. Conclusion. We conclude that the essential role of different MAPK inhibitors is to attenuate the hydrogen peroxide induced neuronal cell damage. Those data broaden the implication between individual neural cells and different MAPK inhibitors and give clues for oxidative stress induced neural diseases.

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“…Generation of intracellular ROS following H 2 O 2 treatment is known to contribute to oxidative stress [ 36 , 37 , 38 ]. To confirm that H 2 O 2 treatment leads to ROS generation and to further understand the modulation of the H 2 O 2 -induced oxidative stress by STING in this study, intracellular ROS levels in H 2 O 2 treated WT and STING −/− cells were measured by a 2′, 7′-dichlorofluorescin (DCF) assay.…”

Section: Resultsmentioning

confidence: 99%

“…These discrepancies observed underscore our lack of understanding of how STING modulates autophagic activity in different disease models. Evidence in the literature has also associated H 2 O 2 -induced oxidative stress with autophagy activation [ 26 , 36 ]. It is possible, therefore, that STING may act as a molecular switch in promoting either detrimental or beneficial outcomes in TBI and H 2 O 2 -induced oxidative stress, respectively, by modulating autophagy activity.…”

Section: Discussionmentioning

confidence: 99%

STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death

Abdullah

Mobilio

Crack

et al. 2020

IJMS

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Stimulator of interferon genes (STING)-mediated type-I interferon signaling is a well characterized instigator of the innate immune response following bacterial or viral infections in the periphery. Emerging evidence has recently linked STING to various neuropathological conditions, however, both protective and deleterious effects of the pathway have been reported. Elevated oxidative stress, such as neuroinflammation, is a feature of a number of neuropathologies, therefore, this study investigated the role of the STING pathway in cell death induced by elevated oxidative stress. Here, we report that the H2O2-induced activation of the STING pathway is protective against cell death in wildtype (WT) MEFSV40 cells as compared to STING−/− MEF SV40 cells. This protective effect of STING can be attributed, in part, to an increase in autophagy flux with an increased LC3II/I ratio identified in H2O2-treated WT cells as compared to STING−/− cells. STING−/− cells also exhibited impaired autophagic flux as indicated by p62, LC3-II and LAMP2 accumulation following H2O2 treatment, suggestive of an impairment at the autophagosome-lysosomal fusion step. This indicates a previously unrecognized role for STING in maintaining efficient autophagy flux and protecting against H2O2-induced cell death. This finding supports a multifaceted role for the STING pathway in the underlying cellular mechanisms contributing to the pathogenesis of neurological disorders.

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Homer1a Attenuates Hydrogen Peroxide-Induced Oxidative Damage in HT-22 Cells through AMPK-Dependent Autophagy

Cited by 15 publications

References 24 publications

Trilobatin Protects Against Oxidative Injury in Neuronal PC12 Cells Through Regulating Mitochondrial ROS Homeostasis Mediated by AMPK/Nrf2/Sirt3 Signaling Pathway

Trilobatin Protects Against Oxidative Injury in Neuronal PC12 Cells Through Regulating Mitochondrial ROS Homeostasis Mediated by AMPK/Nrf2/Sirt3 Signaling Pathway

MAPK Pathway Inhibitors Attenuated Hydrogen Peroxide Induced Damage in Neural Cells

STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death

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