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标题：Folinic Acid Increases Protein Arginine Methylation in Human Endothelial Cells
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作者：Ruben Esse ; Tom Teerlink ; Pieter Koolwijk 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2018
卷号：10
期号：4
页码：404
DOI：10.3390/nu10040404
语种：English
出版社：MDPI Publishing
摘要：Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, but the mechanisms underlying this association are not completely understood. Cellular hypomethylation has been suggested to be a key pathophysiologic mechanism, since S-adenosylhomocysteine (AdoHcy), the Hcy metabolic precursor and a potent inhibitor of methyltransferase activity, accumulates in the setting of hyperhomocysteinemia. In this study, the impact of folate and methionine on intracellular AdoHcy levels and protein arginine methylation status was studied. Human endothelial cells were incubated with increasing concentrations of folinic acid (FnA), a stable precursor of folate, with or without methionine restriction. The levels of intracellular AdoHcy and AdoMet, tHcy in the cell culture medium, and protein-incorporated methylarginines were evaluated by suitable liquid chromatography techniques. FnA supplementation, with or without methionine restriction, reduced the level of tHcy and did not affect intracellular AdoMet levels. Interestingly, FnA supplementation reduced intracellular AdoHcy levels only in cells grown under methionine restriction. Furthermore, these cells also displayed increased protein arginine methylation status. These observations suggest that folic acid supplementation may enhance cellular methylation capacity under a low methionine status. Our results lead us to hypothesize that the putative benefits of folic acid supplementation in restoring endothelial homeostasis, thus preventing atherothrombotic events, should be reevaluated in subjects under a methionine restriction diet.
关键词：folate; homocysteine; cellular methylation capacity; protein arginine methylation folate ; homocysteine ; cellular methylation capacity ; protein arginine methylation