Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells.

Previous studies have demonstrated that apolipoprotein E (ApoE) genotype and melatonin are closely associated with Alzheimer's disease (AD). However, the relationship between ApoE genotype and melatonin remains unclear. Recently, we reported that cultured rat cortical astrocytes and glioma C6 cells synthesize melatonin. In the current study, we investigated the effect of ApoE genotype on melatonin biosynthesis. C6 cells with stable expression of ApoE isoforms (ApoE 2, 3 and 4) were established. A higher level of melatonin was demonstrated in cultured ApoE4-C6 cells than that in ApoE3-C6 cells. In addition, we found that N-acetyltransferase (NAT) protein level was up-regulated in ApoE4-C6 cells compared with ApoE3-C6 cells. Further study suggested that mRNA expression of monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) decreased in ApoE4-C6 cells. In conclusion, the increased melatonin level in ApoE4-C6 cells results from up-regulation of NAT expression, a key enzyme for melatonin synthesis, and down-regulation of MAOA and MAOB expression, the metabolic enzyme for its precursor serotonin.