Neuroprotective Effect of N-Acyl 5-Hydroxytryptamines on Glutamate-Induced Cytotoxicity in HT-22 Cells

Jin, Mei Chen; Yoo, Jae Myung; Sok, Dai‐Eun; Kim, Mee Ree

doi:10.1007/s11064-014-1448-2

Cited by 20 publications

(53 citation statements)

References 42 publications

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“…N-acyl phospholipids are considered aytipical lipids implicated in the biosynthesis of lipid mediators such as endocannabinoids. In parallel, it has been shown that phenolic endocannabinoids like N-acyl 5-HT, present in the brain exert a cytoprotective action against glutamateinduced oxidative damage of HT-22 cells possibly by an Nrf2-mediated mechanism (Jin et al, 2014).…”

Section: Nrf2 and Lipid Metabolismmentioning

confidence: 99%

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Esteras¹,

Dinkova‐Kostova²,

Abramov³

2016

Biological Chemistry

132

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Abstract:The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor wellknown for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.

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Section: Nrf2 and Lipid Metabolismmentioning

confidence: 99%

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Esteras¹,

Dinkova‐Kostova²,

Abramov³

2016

Biological Chemistry

132

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“…It prevented the convulsion in mice administered with pentylenetetrazole [27] , enhanced anxiolytic behavior in the elevated plus maze (EPM) in mice at basolateral amygdale [28] , reduced carrageenan-induced hyperalgesia in mice [29] and decreased anxiety-like behavior in EPM [30] . Recently, NA-5HT was observed to possess anti-allergic and anti-inflammatory actions in mast cells [13,14] . Very recently, NA-5HT was observed to show antioxidant action through activation of Nrf2 signaling in HT-22 cells [14] .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study indicated that N -acyl 5HTs exerted a potent antioxidant action by inducing antioxidant enzymes via the activation of PI3K/Akt signaling in HT-22 cells [14] . In this regard, we examined whether NA-5HT could affect the expression of representative antioxidant enzymes such as GCLC, HO-1 and NQO-1, which were known to suppress oxidative stress [16] .…”

Section: Regulatory Effect Of Na-5ht On Induction Of Antioxidant Enzymentioning

confidence: 99%

“…Previously, NA-5HT, which was found to be present in the vertebrates [10,11] , had been reported to be a mild inhibitor of fatty acid amide hydrolase and an antagonist of transient receptor potential vanilloid 1 channel [12] . Recently, N -acyl 5HTs were reported to show anti-allergic and anti-inflammatory actions in mast cells or nerve cells [13,14] . Besides, some endocannabinoids were known to induce antioxidant enzymes via the activation of nuclear factor-E2-related factor-2 (Nrf2) pathway [15] .…”

Section: Introductionmentioning

confidence: 99%

“…Besides, some endocannabinoids were known to induce antioxidant enzymes via the activation of nuclear factor-E2-related factor-2 (Nrf2) pathway [15] . Our recent study showed that N -palmitoyl 5HT remarkably augmented the level of antioxidant enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) or NAD(P)H quinine oxidoreductase-1 (NQO-1) via the activation of Nrf2 pathway in HT-22 cells [14] . Moreover, an increased level of HO-1 was reported to demonstrate anti-inflammatory action [16] , where oxidative stress was possibly implicated in the induction of inflammatory response [17] .…”

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory and Antioxidant Actions of <b><i>N</i></b>-Arachidonoyl Serotonin in RAW264.7 Cells

Jeon

Yoo²,

Lee³

et al. 2016

Pharmacology

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The purpose of this study is to evaluate the effect of N-arachidonoyl serotonin (NA-5HT) on inflammatory response or oxidative stress in RAW264.7 cells exposed to lipopolysaccharide (LPS). When RAW264.7 cells were pre-incubated with NA-5HT before LPS treatment, NA-5HT was found to suppress LPS-induced formation of nitric oxide (NO), tumor necrosis factor-a or interleukins as well as expression of inducible NO synthase and cyclooxygenase-2 at non-cytotoxic concentrations. Consistent with this, NA-5HT efficiently reversed LPS-induced phosphorylative activation of nuclear factor-κB pathway probably through the suppression of mitogen-activated protein kinases (MAPKs) pathway or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Separately, NA-5HT enhanced the antioxidant capacity accompanied by nuclear translocation of nuclear factor-E2-related factor-2 (Nrf2) in RAW264.7 cells. Additionally, NA-5HT-induced nuclear translocation of Nrf2 was suppressed significantly by the inhibition of c-Jun N-terminal kinase1/2 or PI3K/Akt pathways, although NA-5HT phosphorylated signal molecules in MAPKs and PI3K/Akt pathways. Taken together, NA-5HT is proposed to exert anti-inflammatory and antioxidant actions in RAW264.7 cells.

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Anti‐Apoptotic Effect of N‐Palmitoyl Serotonin on Glutamate‐Mediated Apoptosis Through Secretion of BDNF and Activation of TrkB/CREB Pathway in HT‐22 Cells

Yoo

Lee

et al. 2017

Euro J Lipid Sci & Tech

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Recently, N‐acyl serotonins have been reported to exert neuroprotective actions against oxidative stress by inducing antioxidant enzymes. However, the mechanisms for the neuroprotective action of N‐acyl serotonins are still not clarified. In this study, we focuse on the suppressive effect of N‐palmitoyl serotonin on glutamate‐induced apoptosis in HT‐22 cells, and then examine the molecular mechanism for anti‐apoptotic action of N‐palmitoyl serotonin. For this purpose, flow cytometry, immunoblotting analysis and antibody‐mediated neutralization is formed. When HT‐22 cells are preincubated with N‐palmitoyl serotonin prior to glutamate treatment, N‐palmitoyl serotonin dose‐dependently reduces apoptotic bodies, and recoveres mitochondrial potential in glutamate‐treated HT‐22 cells. Further, N‐palmitoyl serotonin concentration‐dependently increases the expression of B‐cell lymphoma 2 (Bcl‐2), an anti‐apoptotic factor, whereas it reduces the expression of Bcl‐2‐associated X protein, apoptosis‐inducing factor, Ca2+‐dependent non‐lysosomal cysteine protease, cytochrome c, and cleaves caspase‐3. Meanwhile, N‐palmitoyl serotonin enhanced phosphorylation of tropomyosin‐related kinase receptors (TrkB) and cAMP response element‐binding protein (CREB) as well as expression of brain‐derived neurotrophic factor (BDNF). Separately, the inclusion of anti‐BDNF antibody neutralizes the neuroprotective action of N‐palmitoyl serotonin against glutamate‐induced cell death. In addition, K252a, a TrkB inhibitor, also reverses neuroprotective effect of N‐palmitoyl serotonin, suggesting that the action of N‐palmitoyl serotonin may be expressed through the formation of BDNF. Based on these results, it is proposed that N‐palmitoyl serotonin promotes formation and secretion of BDNF, and then protects neuronal cells against oxidative stress‐induced apoptosis through activation of TrkB/CREB pathway. Practical Applications: The results may provide further information for the application of N‐acyl serotonins as a therapeutic or preventive agent for neurodegenerative diseases. N‐Palmitoyl 2 serotonin (Pal‐5HT) not only induces brain‐derived neurotrophic factor (BDNF) expression but also protects neuronal cells against oxidative stress.

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Neuroprotective Effect of N-Acyl 5-Hydroxytryptamines on Glutamate-Induced Cytotoxicity in HT-22 Cells

Cited by 20 publications

References 42 publications

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Anti-Inflammatory and Antioxidant Actions of <b><i>N</i></b>-Arachidonoyl Serotonin in RAW264.7 Cells

Anti‐Apoptotic Effect of N‐Palmitoyl Serotonin on Glutamate‐Mediated Apoptosis Through Secretion of BDNF and Activation of TrkB/CREB Pathway in HT‐22 Cells

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