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N-acetyl serotonin protects neuronal cell death induced by oxidative stress via elevation of TrkB/CREB/BDNF and Akt/Nrf2 pathways
7th World Congress on Chemistry
November 13-15, 2017 Athens, Greece
Mee Ree Kim
Chungnam National University, South Korea
Scientific Tracks Abstracts : J Biotech and Phyto
Abstract:
Recently, N-acyl serotonin, present in the intestine, has been reported to exert neuroprotective action against oxidative stress by inducing antioxidant enzymes. However, the mechanism for neuroprotective action of N-acetyl serotonin(NAS) as a precursor of melatonin is not clarified. In this study we focused on the suppressive effect of N-acetyl serotonin on glutamate-induced apoptosis in HT-22 cells, and then examined the molecular mechanism for its antiapoptotic action. For this purpose, we performed flow cytometry, immunoblotting analyses and antibody-mediated neutralization. When HT-22 cells were preincubated with NAS prior to glutamate treatment, NAS dose-dependently reduced apoptotic bodies and recovered mitochondrial potential in glutamate-treated HT-22 cells. NAS dose-dependently inhibited oxidative stress-induced cell death in HT-22 cells. Moreover, NAS suppressed glutamate-induced apoptosis by suppressing expression of pro-apoptotic factors such as AIF, Bax, calpain, cytochrome c and cleaved caspase-3, whereas it enhanced expression of Bcl-2, an anti-apoptotic factor. In addition, NAS improved phosphorylation of tropomyosin related kinase receptor (TrkB) and cAMP response elementbinding 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 dosedependently reduced the level of reactive oxygen species, and enhanced the level of glutathione in glutamate-treated HT-22 cells. Moreover, NAS not only increased expression of heme oxygenase-1, NAD(P)H quinine oxidoreductase-1 and glutamate-cysteine ligase catalytic subunit, but also enhanced 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 stressinduced neurotoxicity. Therefore, such effects of NAS may provide the information for the application of NAS against neurodegenerative diseases.
Biography:
Mee Ree Kim has completed her PhD from Seoul National University and is a Visiting Professor at Wisconsin-Madison University, Department of Toxicology. She is the former President of Korean Food Related Academic Association. She has published more than 120 papers in reputed journals and has been serving as an Editorial Board Member of repute such as Journal of Medicinal Food.
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