Inhibition of phosphatidylserine biosynthesis in developing rat brain by maternal exposure to ethanol.

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Wen Z, Kim HY

Inhibition of phosphatidylserine biosynthesis in developing rat brain by maternal exposure to ethanol.

J Neurosci Res. 2007 May 15;85(7):1568-78.

PubMed ID

17387686 [ View in PubMed

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Abstract

Phosphatidylserine (PtdSer), major acidic phospholipids in neuronal membranes, participate in important cell signaling processes. The PtdSer in brain is highly enriched with docosahexaenoic acid (DHA; 22:6n-3), and the DHA status or ethanol exposure has been shown to influence the PtdSer level. This study shows that ethanol exposure during prenatal and developmental period significantly attenuates microsomal PtdSer biosynthetic activities and reduces PtdSer, particularly 18:0, 22:6-PtdSer, in developing rat brain cortices. Brain microsomes were incubated with deuterium labeled exogenous substrates in vitro and the products formed were detected by reversed phase HPLC-electrospray ionization mass spectrometry (ESI-MS). These in vitro bioassays showed that 1-stearoyl-2-docosahexaenoyl (18:0, 22:6) species is the best substrate for PtdSer synthesis from both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn). The PtdSer biosynthetic activity of brain, especially for 18:0, 22:6-PtdSer production, was hampered significantly by maternal exposure to ethanol. PtdSer levels were consistently reduced significantly in brain cortices of the pups from ethanol-exposed dams, due mainly to the depletion of 18:0, 22:6-PtdSer. The mRNA expression of PtdSer synthase 1 (PSS1) and PtdSer synthase 2 (PSS2) was not reduced by ethanol. Similarly, the PSS1 enzyme level did not change after ethanol exposure but PSS2 could not be probed with the antibody available currently. Degradation of PtdSer by mitochondrial PtdSer decarboxylation was not enhanced but also inhibited. Taken together, attenuated PtdSer biosynthetic activities are largely responsible for the PtdSer reduction observed in developing rat brains after maternal exposure to ethanol.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phosphatidyl serine	Phosphatidylserine synthase 2	Protein	Humans	Unknown	Not Available	Details