Effect of lipopolysaccharide (LPS) on HAEC cells. Does nicotinamide N-methyltransferase sensitize HAEC cells to LPS?

Abstract

Treatment of endothelial cells with bacterial lipopolysaccharide (LPS) evokes a number of metabolic and functional consequences which built a multifaceted physiological response of endothelium to bacterial infection. Here effects of LPS on human aortic endothelial cells (HAEC) have been investigated. Among the spectrum of biochemical changes substantially elevated N-nicotinamide methyltransferase (NNMT) protein level was particularly intriguing. It has been shown that silencing of the NNMT-encoding gene prevented several changes which are observed in control HAECs due to treatment with LPS. They include significantly increased cytosolic Ca2+ concentration and abnormally strong calcium response to thapsigargin, altered energy metabolism which is switched to anaerobic glycolysis and rearrangement of the mitochondrial network organization. Biochemical mechanisms behind protecting effect of partial NNMT deficiency remains unknown but we speculate that the primary role in this phenomenon is attributed to normalized Ca2+ response in cells partially deprived of the NNMT gene. However, this assumption needs to be verified experimentally. Nevertheless, this paper focuses the reader attention on NNMT, which is an important enzyme that potentially may affect cellular metabolism by two means: direct influence based on a regulation of NAD+ synthesis through modulation of nicotinamide availability, and a regulation of S-adenosylmethionine concentration and therefore controlling of methylation processes including modification of chromatin and epigenetic effects