NADPH oxidase: A possible link between lipoprotein lipase hydrolysis products-induced ROS production and snoRNA overexpression in macrophages.

Mariam Tijani
M.Sc Student
Department of Biochemistry

Date: October 23, 2023
Time: 1:00-2:00 p.m.
Room: CSF-1302

Lipids are a crucial part of the human body's homeostatic process. Lipoproteins, a complex assembly of lipid and protein, carries lipids through the blood to different tissues. Lipoprotein lipase (LPL) hydrolyzes the triglycerides and phospholipids transported in lipoproteins to release free fatty acids (FFA) for the cell’s needs.  High serum lipid levels are strongly related to the development of atherosclerosis. An increase in FFA was found to contribute to one of the fundamental pathogenetic processes of atherosclerosis, oxidative stress. Oxidative stress is marked by increased reactive oxygen species (ROS) generation. ROS are produced from multiple cellular processes and by specialized enzymes, including nicotinamide adenine dinucleotide phosphate oxidases (NOX) in the cell. At high concentrations, excess cellular levels of ROS trigger oxidative stress, causing excessive oxidative damage to proteins, nucleic acids, lipids, membranes, and organelles such as mitochondria. Prior studies from our laboratory have shown increased expression of transcripts related to endoplasmic reticulum (ER) stress, and also the overexpression of 63 small nucleolar RNAs (snoRNA) in macrophages treated with lipid hydrolysis products generated by LPL. The mediators of these transcript changes are unclear. The aim of this research is to determine if NOX is a mediator of lipoprotein lipid hydrolysis product-induced ROS production and if this ultimately results in the overexpression of snoRNAs. Lipid hydrolysis products-induced ROS production, lipid peroxidation, RNA integrity, and expression of snoRNAs will be analyzed in macrophages, with or without NOX inhibitors. It is anticipated that lipoprotein lipid hydrolysis products made by LPL are the mediator between ROS production by NOX, and snoRNA overexpression in macrophages.