Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells
| العنوان: | Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells |
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| المؤلفون: | Bo Dam Lee, Jae-Myung Yoo, Jin Yuel Ma, Mee Ree Kim, Dai-Eun Sok |
| المصدر: | Redox Biology Redox Biology, Vol 11, Iss, Pp 592-599 (2017) |
| بيانات النشر: | Elsevier, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, MAPK/ERK pathway, Bcl-2, B-cell lymphoma 2, Clinical Biochemistry, MAPK, Mitogen-activated protein kinase, Apoptosis, Tropomyosin receptor kinase B, medicine.disease_cause, GCLC, Glutamate-cysteine ligase catalytic subunit, Biochemistry, Antioxidants, Mice, 0302 clinical medicine, Akt, Protein kinase B, Phosphorylation, Cyclic AMP Response Element-Binding Protein, lcsh:QH301-705.5, GSH, Glutathione, Neurons, lcsh:R5-920, Membrane Glycoproteins, biology, ERK, Extracellular signal-regulated kinase 1/2, NQO-1, NAD(P)H quinine oxidoreductase-1, DCFDA, 2, 7-Dichlorofluorescein diacetate, AIF, Apoptosis-inducing factor, Memory impairment, TrkB, Tropomyosin-related kinase receptor B, Neuroprotection, Cell biology, Oncogene Protein v-akt, N-acetyl serotonin, JNK, c-Jun N-terminal kinase 1/2, Antioxidant enzymes, HO-1, Heme oxygenase-1, lcsh:Medicine (General), Research Paper, Programmed cell death, Serotonin, NAS, N-acetyl serotonin, NF-E2-Related Factor 2, CREB, 03 medical and health sciences, Nrf2, NF-E2-related factor-2, medicine, Animals, Humans, Receptor, trkB, Protein kinase B, BDNF, Brain-derived neurotrophic factor, Brain-Derived Neurotrophic Factor, Organic Chemistry, Neurotoxicity, medicine.disease, Bax, Bcl-2-associated X protein, Oxidative Stress, 030104 developmental biology, BDNF, lcsh:Biology (General), biology.protein, CREB, cAMP response element-binding protein, calpain, Ca2+-dependent, non-lysosomal cysteine protease, 030217 neurology & neurosurgery, Oxidative stress, ROS, Reactive oxygen species |
| الوصف: | N-acetyl serotonin (NAS) as a melatonin precursor has neuroprotective actions. Nonetheless, it is not clarified how NAS protects neuronal cells against oxidative stress. Recently, we have reported that N-palmitoyl serotonins possessed properties of antioxidants and neuroprotection. Based on those, we hypothesized that NAS, a N-acyl serotonin, may have similar actions in oxidative stress-induced neuronal cells, and examined the effects of NAS based on in vitro and in vivo tests. NAS dose-dependently inhibited oxidative stress-induced cell death in HT-22 cells. Moreover, NAS suppressed glutamate-induced apoptosis by suppressing expression of AIF, Bax, calpain, cytochrome c and cleaved caspase-3, whereas it enhanced expression of Bcl-2. Additionally, NAS improved phosphorylation of tropomyosin-related kinase receptor B (TrkB) and cAMP response element-binding protein (CREB) as well as expression of brain-derived neurotrophic factor (BDNF), whereas the inclusion of each inhibitor of JNK, p38 or Akt neutralized the neuroprotective effect of NAS, but not that of ERK. Meanwhile, NAS dose-dependently reduced the level of reactive oxygen species, and enhanced the level of glutathione in glutamate-treated HT-22 cells. Moreover, NAS significantly increased expression of heme oxygenase-1, NAD(P)H quinine oxidoreductase-1 and glutamate-cysteine ligase catalytic subunit as well as nuclear translocation of NF-E2-related factor-2. Separately, NAS at 30 mg/kg suppressed scopolamine-induced memory impairment and cell death in CA1 and CA3 regions in mice. In conclusion, NAS shows actions of antioxidant and anti-apoptosis by activating TrkB/CREB/BDNF pathway and expression of antioxidant enzymes in oxidative stress-induced neurotoxicity. Therefore, such effects of NAS may provide the information for the application of NAS against neurodegenerative diseases. Graphical abstract fx1 Highlights • NAS protects apoptosis induced by oxidative stress in neuronal cells. • NAS exerts an antioxidant property in neuronal cells. • NAS improves activation of BDNF/TrkB/CREB pathway in neuronal cells. • NAS enhances activation of Akt/Nrf2/Antioxidant enzyme pathway in neuronal cells. • NAS recovers memory and neuronal cells in scopolamine-treated mice. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5666541f328d5af707133ed7df75f1bc http://europepmc.org/articles/PMC5247570 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5666541f328d5af707133ed7df75f1bc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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