No abstract

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.

No abstract

Human embryonic stem (hES) cells can be maintained in a proliferative undifferentiated state in vitro by growing them on feeder layers of mouse embryonic fibroblast (MEF) cells along with basic fibroblast growth factor (bFGF/FGF-2). To understand the molecular mechanisms involved in the requirement of bFGF in human ES cells, we investigated expression of FGF receptors and intracellular signaling events in response to bFGF in human ES cell line MizhES1. On the basis of the results of RT-PCR, clear expression of FGF receptors FGFR1, FGR2, and FGFR3 was noticed. Because MAPK, PI3K, and PKC pathways are well-known pathways triggered by bFGF in other cells, these pathways were investigated after stimulation with bFGF. bFGF did not induce activation of PI3K or PKC, but induced activation of ERK (extracellular signal-regulated kinase). To monitor the consequences of ERK activation, we examined expression of the immediate early gene c-fos, one downstream target of the MEK1/ERK pathway. mRNA and protein levels of the c-fos gene were increased by bFGF. Induction of c-Fos was dependent on MEKl. Therefore, it is likely that bFGF contributes to maintenance of human ES cells, at least in part, through the MEK1/ERK pathway.

These results indicated that the pro-inflammatory activity of saturated acyl LPCs could be antagonized by the actions of polyunsaturated acyl LPCs, anti-inflammatory lipid mediators.