摘要

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.

  • 出版日期2018-2