Lipopolysaccharide affects energy metabolism and elevates nicotinamide N-methyltransferase level in human aortic endothelial cells (HAEC).

Abstract

This study aimed to investigate the putative role of nicotinamide N-methyltransferase in the metabolic response of human aortic endothelial cells. This enzyme catalyses S-adenosylmethionine-mediated methylation of nicotinamide to methylnicotinamide. This reaction is accompanied by the reduction of the intracellular nicotinamide and S-adenosylmethionine content. This may affect NAD+ synthesis and various processes of methylation, including epigenetic modifications of chromatin. Particularly high activity of nicotinamide N-methyltransferase is detected in liver, many neoplasms as well as in various cells in stressful conditions. The elevated nicotinamide N-methyltransferase content was also found in endothelial cells treated with statins. Although the exogenous methylnicotinamide has been postulated to induce a vasodilatory response, the specific metabolic role of nicotinamide N-methyltransferase in vascular endothelium is still unclear. Treatment of endothelial cells with bacterial lipopolysaccharide evokes several metabolic and functional consequences which built a multifaceted physiological response of endothelium to bacterial infection. Among the spectrum of biochemical changes substantially elevated protein level of nicotinamide N-methyltransferase was particularly intriguing. Here it has been shown that silencing of the nicotinamide N-methyltransferase gene influences several changes which are observed in cells treated with lipopolysaccharide. They include altered energy metabolism and rearrangement of the mitochondrial network. A complete explanation of the mechanisms behind the protective consequences of the nicotinamide N-methyltransferase deficiency in cells treated with lipopolysaccharide needs further investigation.

• Authors: Oksana Stępińska, Dorota Dymkowska, Łukasz Mateuszuk, Krzysztof Zabłocki
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 151 Pg. 106292 (10 2022) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 36038127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Chromatin
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipopolysaccharides
• NAD
• Niacinamide
• S-Adenosylmethionine
• Nicotinamide N-Methyltransferase

Topics

• Chromatin (metabolism)
• Endothelial Cells (metabolism)
• Endothelium (metabolism)
• Energy Metabolism
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipopolysaccharides (pharmacology)
• NAD (metabolism)
• Niacinamide (metabolism, pharmacology)
• Nicotinamide N-Methyltransferase (genetics, metabolism)
• S-Adenosylmethionine (metabolism)