Quantitative proteomics reveals decreased expression of major urinary proteins in the liver of apoE/eNOS‐DKO mice

• Published in: Clinical and experimental pharmacology & physiology Vol. 45; no. 7; pp. 711 - 719
• Main Authors: Stachowicz, Aneta, Olszanecki, Rafał, Suski, Maciej, Wiśniewska, Anna, Kuś, Katarzyna, Białas, Magdalena, Jawień, Jacek, Korbut, Ryszard
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01-07-2018
• Subjects: Apolipoprotein E; Arteriosclerosis; Atherosclerosis; Biosynthesis; Cholesterol; Electron transport; Endoplasmic reticulum; endothelial NOS; Endothelium; Fatty acids; Fatty liver; Gluconeogenesis; Glucose; Glucose metabolism; Homeostasis; Lipid metabolism; Liver; major urinary proteins; Metabolism; Mice; Mitochondria; Nitric oxide; Nitric-oxide synthase; Protein transport; Proteins; Proteomics; Rodents; Steatosis; Transcription; Vasodilation; apolipoprotein E; major urinary proteins; endothelial NOS; proteomics; liver
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12927

Summary
Endothelial nitric oxide synthase (eNOS)‐derived nitric oxide (NO) plays an important role, not only in endothelium‐dependent vasodilation but also in lipid and glucose homeostasis in the liver and exerts beneficial effects on mitochondrial biogenesis and respiration. Thus, the aim of our study was to use iTRAQ‐based quantitative proteomics to investigate the changes in protein expression in the mitochondrial and cytosolic fractions isolated from the liver of the double (apolipoprotein E (apoE) and eNOS) knockout (apoE/eNOS‐DKO) mice as compared to apoE KO mice (apoE−/−) – an animal model of atherosclerosis and hepatic steatosis. Collectively, the deficiency of eNOS resulted in increased expression of proteins related to gluconeogenesis, fatty acids and cholesterol biosynthesis as well as the decreased expression of proteins participated in triglyceride breakdown, cholesterol transport, protein transcription & translation and processing in endoplasmic reticulum (ER). Moreover, one of the most downregulated proteins were major urinary proteins (MUPs), which are abundantly expressed in the liver and were shown to be involved in the regulation of lipid and glucose metabolism. The exact functional consequences of the revealed alterations require further investigation.