NADPH oxidases promote apoptosis by activating ZNRF1 ubiquitin ligase in neurons treated with an exogenously applied oxidant

Wakatsuki, Soichi; Araki, Toshiyuki

doi:10.1080/19420889.2016.1143575

Cited by 14 publications

(10 citation statements)

References 9 publications

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“…Mounting evidence now suggests an increase in the level of activated EGFR (p-EGFR/EGFR) in the adult brains of neurodegenerative diseases, such as AD, Parkinson's disease, and ALS, as well as brain and spinal cord injuries. This activation and upregulation of EGFR are reported in both reactive astrocytes and neurons (Liu and Neufeld, 2004;Zhang and Neufeld, 2005;Liu et al, 2006;Erschbamer et al, 2007;Li et al, 2011Li et al, , 2014Yang et al, 2011;Qu et al, 2012;Wang et al, 2012aWang et al, , 2013Kjell et al, 2014;Wakatsuki et al, 2015;Wakatsuki and Araki, 2016;Zhang et al, 2016;Chen et al, 2017).…”

Section: Egfr Expression Level and Its Role Inmentioning

confidence: 82%

“…In the adult brain, injuries and pathologic conditions activate EGFR in both neurons and astrocytes (Liu and Neufeld, 2004;Zhang and Neufeld, 2005;Liu et al, 2006;Wakatsuki et al, 2015;Wakatsuki and Araki, 2016;Chen et al, 2017). This includes Huntington disease (Gu et al, 2005;Faideau et al, 2010;Abjean et al, 2018), AD (Jo et al, 2014;Ceyzériat et al, 2018), Parkinson's disease (Bandopadhyay et al, 2004;Neumann et al, 2004;Koprich et al, 2008), ALS (Kushner et al, 1991;Tripathi et al, 2017), amyloid structure formation such as a-synuclein (Chavarría et al, 2018;Duffy et al, 2018) and b-amyloid (Pike et al, 1994;Söllvander et al, 2016), and traumatic brain injuries such as weight-drop technique (Erschbamer et al, 2007;Li et al, 2011Li et al, , 2014Qu et al, 2012;Kjell et al, 2014;Shandra et al, 2019), oxygen/glucose deprivation (OGD) (Wang et al, 2012b;Liu et al, 2019), and ischemic injury (Morizawa et al, 2017;Laug et al, 2019).…”

Section: Egfr Activation In the Pathologic Adult Brainmentioning

confidence: 99%

“…1). Besides the indirect effect of EGFR activation in reactive astrocytes on neuronal degeneration, it has been reported that oxidative stress can directly activate EGFR in neuronal cells and finally lead to degeneration and apoptosis in neurons (Wakatsuki et al, 2015;Wakatsuki and Araki, 2016). Oxidative stress induced by treatment of neuronal cells with 6-hydroxydopamine or H 2 O 2 as well as in vivo by traumatic injury induction in animals, which causes the generation of NADPH oxidases in axons, stimulates neuronal EGFR tyrosine kinase activity.…”

Section: Egfr Activation In the Pathologic Adult Brainmentioning

confidence: 99%

“…causes microtubule disassembly and axonal degeneration (Wakatsuki et al, 2015;Wakatsuki and Araki, 2016). The same pathway in soma activates EGFR and downstream ZNRF1 signaling pathway, which leads to an increase in the caspase 3 cleavage, annexin V-positive staining, lactate dehydrogenase release, and neuronal apoptosis.…”

Section: Egfr Activation In the Pathologic Adult Brainmentioning

confidence: 99%

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Inhibition of Brain Epidermal Growth Factor Receptor Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries

2020

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Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathologic and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal cord injuries (SCI). Despite successful therapeutic effects of EGFR inhibition in these pathologic conditions, there is still no report of proof-of-concept studies in well-characterized animal models using recently developed blood-brain barrier (BBB)-penetrating EGFR inhibitors, which is due to previous conflicting reports concerning the level of EGFR or activated EGFR in normal and pathologic conditions that caused target engagement to be a concern in any future EGFR inhibition therapy. In this review, the level of EGFR expression and activation in the developing central nervous system (CNS) compared with the adult CNS will be explained as well as how neuronal injury or pathologic conditions, especially inflammation and amyloid fibrils, induce reactive astrocytes leading to an increase in the expression and activation of EGFR and, finally, neurodegeneration. Furthermore, in this review, we will discuss two main molecular mechanisms that can be proposed as the neuroprotective effects of EGFR inhibition in these pathologic conditions. We will also review the recent advances in the development of BBB-penetrating EGFR inhibitors in cancer therapy, which may eventually be repositioned for NDDs and SCI therapy in the future. SIGNIFICANCE STATEMENTBased on the lessons from the applications of EGFR inhibitors in oncology, it is concluded that EGFR inhibitors can be beneficial in treatment of neurodegenerative diseases and spinal cord injuries. They carry their therapeutic potentials through induction of autophagy and attenuation of reactive astrocytes.O.T. is supported by a grant from the W. Garfield Weston Foundation (Weston Brain Institute) [RR171033].

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Section: Egfr Expression Level and Its Role Inmentioning

confidence: 82%

Section: Egfr Activation In the Pathologic Adult Brainmentioning

confidence: 99%

Section: Egfr Activation In the Pathologic Adult Brainmentioning

confidence: 99%

Section: Egfr Activation In the Pathologic Adult Brainmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Brain Epidermal Growth Factor Receptor Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries

2020

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“…Previous studies have shown that proteolysis‐inducing factor (PIF) and angiotensin II induce protein degradation through the activation of NADPH oxidase in murine myotube . Wakatsuki et al reported that activated NADPH oxidase induces the activation of a ubiquitin ligase ZNRF1 (Zinc‐ and RING‐finger 1), which elicits proteasomal degradation of AKT in neurons. Other studies have shown that oxidized proteins are subjected to proteasome degradation .…”

Section: Resultsmentioning

confidence: 99%

SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells

Wang

Chiou

Lee

et al. 2020

J Cellular Molecular Medi

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The contribution of vincristine (VCR)‐induced microtubule destabilization to evoke apoptosis in cancer cells remains to be resolved. Thus, we investigated the cytotoxic mechanism of VCR on U937 and HL‐60 human leukaemia cell lines. We discovered that VCR treatment resulted in the up‐regulation of TNF‐α expression and activation of the death receptor pathway, which evoked apoptosis of U937 cells. Moreover, VCR induced microtubule destabilization and mitotic arrest. VCR treatment down‐regulated SIRT3, and such down‐regulation caused mitochondrial ROS to initiate phosphorylation of p38 MAPK. p38 MAPK suppressed MID1‐modulated degradation of the protein phosphatase 2A (PP2A) catalytic subunit. The SIRT3‐ROS‐p38 MAPK‐PP2A axis inhibited tristetraprolin (TTP)‐controlled TNF‐α mRNA degradation, consequently, up‐regulating TNF‐α expression. Restoration of SIRT3 and TTP expression, or inhibition of the ROS‐p38 MAPK axis increased the survival of VCR‐treated cells and repressed TNF‐α up‐regulation. In contrast to suppression of the ROS‐p38 MAPK axis, overexpression of SIRT3 modestly inhibited the effect of VCR on microtubule destabilization and mitotic arrest in U937 cells. Apoptosis of HL‐60 cells, similarly, went through the same pathway. Collectively, our data indicate that the SIRT3‐ROS‐p38 MAPK‐PP2A‐TTP axis modulates TNF‐α expression, which triggers apoptosis of VCR‐treated U937 and HL‐60 cells. We also demonstrate that the apoptotic signalling is not affected by VCR‐elicited microtubule destabilization.

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Concanavalin A Induces Cortical Neuron Apoptosis by Causing ROS Accumulation and Tyrosine Kinase Activation

Jang¹,

Yayeh²,

Leem³

et al. 2017

Neurochem Res

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The lectin, concanavalin A (Con A), is the most extensively investigated member of the lectin family of plant proteins, but its effects on cortical neurons and astrocytes are poorly understood. In cultured cortical neurons and astrocytes, Con A exhibited dose-dependent neurotoxicity, but this was not observed in astrocytes. Similarly, in the cortical areas of rat brains, intracranial administration of Con A caused neuronal but no astrocyte damage. Methyl-α-D-mannopyranoside, a competitor of Con A, blocked Con A-induced cell death, whereas AMPA/KA receptor antagonists showed partial blocking effects. Furthermore, the mRNA levels of TNF-α, IL-1β, and IL-6 were elevated in astrocytes and cortical neurons treated with Con A. Intracellular reactive oxygen species (ROS) levels were increased in Con A-treated cortical neurons, and N-acetyl-cysteine (NAC, an antioxidant) and diphenyleneiodonium (DPI, a NADPH oxidase inhibitor) reduced intracellular ROS accumulation. Likewise, AG556 (a TNF-α inhibitor) and AG82 (a tyrosine kinase inhibitor) both reduced Con A-induced intracellular ROS accumulation. Furthermore, Con A-induced tyrosine phosphorylation was decreased by NAC and by AG556. Taken together, Con A-induced apoptosis in cortical neurons occurred as a sequel to Con A binding to neuronal glycoproteins and intracellular ROS accumulation. Interestingly, Con A-induced cellular damage was observed in cortical neurons but not in astrocytes or microglia.

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NADPH oxidases promote apoptosis by activating ZNRF1 ubiquitin ligase in neurons treated with an exogenously applied oxidant

Cited by 14 publications

References 9 publications

Inhibition of Brain Epidermal Growth Factor Receptor Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries

Inhibition of Brain Epidermal Growth Factor Receptor Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries

SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells

Concanavalin A Induces Cortical Neuron Apoptosis by Causing ROS Accumulation and Tyrosine Kinase Activation

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