Next Thursday 24th June, at 3pm, Oksana Makoveychuk, a PhD student from the Laboratory of Cellular Metabolism led by prof. Krzysztof Zabłocki, will give a lecture entitled: Role of nicotinamide N-methyltransferase in the LPS-induced endothelial dysfunction
The vascular endothelium is an endocrine organ that lines the inner walls of all blood vessels in the human body. Until the 1980s, it was considered only a "cellophane cover", however, it turned out that it has numerous functions related to maintaining blood pressure, homeostasis, hormone transport or a pro-inflammatory response. Because of its location endothelium monolayer is notably exposed to bacterial toxins, which may impact endothelial key functions.
Nicotinamide N-methyltransferase (NNMT, EC 22.214.171.124.) is a cytosolic enzyme that catalyzes the methylation reaction of nicotinamide (MNA) to form N1-methylnicotinamide (MNAM) while consuming the methyl donor S-Adenosyl methionine (SAM). Its role has been underestimating for years considering that NNMT is only a vitamin B3 clearance enzyme but further research on liver, cancer and adipose cells have disproved this theory. In mentioned organs it has already been shown that NNMT may affect different metabolic pathways through depleting of methyl donors and producing active metabolites but its role in endothelium still remains unknown.
We found that treatment of Human Endothelial Aortic Cells with bacterial lipopolisacharide cause increase in NNMT protein level. To shed some light on biochemical mechanisms linking the NNMT activity and mitochondrial energy metabolism further experiments compared the response to LPS in cells with silenced NNMT and normal levels of this protein. Data shown significant differences between those two groups, pointing to the protective effect of NNMT silencing on endothelial response to septic-like conditions. Differences were found in such important aspects as mitochondrial network structure organization, level of some mitochondrial fission/fusion and mitochondrial biogenesis-related proteins, ROS production, calcium level or glycolysis and Crebs cycle metabolites level.
This findings may indicate that NNMT is a potential important target involved in endothelial defense response to inflammatory stimuli but the precise role of this enzyme under such challenging conditions needs to be elucidated.
Meeting ID: 966 1729 0469