Folinic acid increases protein arginine methylation in human endothelial cells

Ruben Esse, Tom Teerlink, Pieter Koolwijk, Isabel Tavares de Almeida, Henk J. Blom, Rita Castro

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 culturemedium, and protein-incorporatedmethylarginineswere 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.
Original languageEnglish
Article number404
JournalNutrients
Volume10
Issue number4
DOIs
Publication statusPublished - 2018

Cite this

Esse, R., Teerlink, T., Koolwijk, P., Tavares de Almeida, I., Blom, H. J., & Castro, R. (2018). Folinic acid increases protein arginine methylation in human endothelial cells. Nutrients, 10(4), [404]. https://doi.org/10.3390/nu10040404