NCoR1 – coordinator of cholesterol metabolism
Cholesterol metabolism is regulated by the corepressor of 1 liver cells
It is well known that in the vast majority of cases these diseases are provoked by a change in the state of the vascular wall after the introduction of cholesterol contained in the blood into it (Nabel, Braunwald, A Tale of Coronary Artery Disease and Myocardial Infarction // N. Engl. J. Med., 2012; A new look at the development of atherosclerosis).
Cholesterol is a substance that is extremely necessary for the vital activity of the body. Almost 80% of it is used for the production of bile acids by hepatocytes (liver cells), the synthesis of steroid hormones (in the adrenal glands and gonads), the formation of myelin sheaths and other structures of nervous tissue; it is also part of cell membranes as a specific stabilizer, etc. About one third of the required amount enters the human body with food every day cholesterol, called exogenous; the other two-thirds are synthesized by the tissues of the body (such cholesterol is called endogenous), in particular, it is produced by liver cells (80%), the walls of the small intestine (10%) and skin (5%).
For the synthesis of endogenous cholesterol, products of the metabolism of amino acids, fats and carbohydrates are used, mainly acetyl-coenzyme A. Consequently, when high-calorie products enter the gastrointestinal tract, an increased amount of cholesterol is formed and the content of low-density lipoproteins in the blood increases, which provokes atherosclerotic changes in the vessels. However, in some patients, intensive cholesterol production is not associated with dietary factors, but depends on a violation of the regulation of this process in the tissues of the body; in this case, even a low-calorie diet is not able to protect against increased cholesterol synthesis and the subsequent development of atherosclerosis. Therefore, the issue of regulation of cholesterol does not lose its relevance and requires further study.
It is known that the concentration of cholesterol in the blood is influenced by numerous factors. Firstly, it is the intensity of the formation of bile acids in the liver, the rate of excretion of cholesterol with bile into the intestine and the degree of absorption of cholesterol by the tissues of the body. Secondly, the metabolism of cholesterol is actively influenced by the endocrine system, for example, thyroid hormones, somatotropic hormone, insulin, adrenal hormones and a number of special bioregulators, such as the liver X receptor (more precisely, its two forms - LXR–alfa and LXR-beta), etc. Nevertheless, the main coordinators of the processes of absorption of food cholesterol in the intestine and synthesis of endogenous cholesterol in the liver have not yet been identified.
A group of scientists from the USA led by Inna Astapova conducted a complex experimental study to test the hypothesis that the main coordinating regulator of cholesterol metabolism is corepressor 1, conventionally designated as NCoR1. This substance is located inside the nuclei of cells; it is represented by a small molecule capable of binding to a special protein that affects the functioning of one of the DNA sites. Scientists, by influencing the genetic apparatus, obtained laboratory animals with a deficiency of a number of receptors and corepressors (including NCoR1) in liver cells, after which metabolic changes in the body of these animals associated with cholesterol metabolism were analyzed in detail.
As a result of the study, it was found that the NCoR1 corepressor of liver cell nuclei effectively affects a number of biochemical processes, during which the activity of certain enzymes increases, the conversion of cholesterol into bile acids increases, the absorption of cholesterol in the intestine decreases, its concentration in the blood decreases, etc. In addition, NCoR1 interacts with cellular receptors of thyroid hormones, thereby changing the intensity of metabolic reactions associated with the synthesis and metabolism of cholesterol in body tissues (Astapova et al., Hepatic nuclear corepressor 1 regulates cholesterol absorption through a TRbeta1-governed pathway // J. Clin. Invest., 2014).
Thus, it has been proved that the corepressor 1 of the nuclei of liver cells (NCoR1) is able to actively regulate the concentration of cholesterol in the blood, and the development of pharmaceuticals that affect NCoR1 is a new promising direction in the prevention and treatment of atherosclerosis.
Portal "Eternal youth" http://vechnayamolodost.ru03.06.2014