Апелин: Адам ағзасындағы маңызды белок

Mammalian protein found in Homo sapiens

Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene. Apelin is one of two endogenous ligands for the G protein coupled APJ receptor that is expressed at the surface of some cell types. It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.

Apelin is a peptide hormone that was identified in 1998 by Masahiko Fujino and his colleagues at Gunma University and Takeda Pharmaceutical Company. Recently, 46 different apelin peptides ranging from apelin 55 to apelin 12 have been identified in bovine colostrum, including C ter truncated isoforms.

The sites of receptor expression are linked to the different functions played by apelin in the organism.

Vascular expression of the receptor participates in the control of blood pressure The blood pressure lowering (hypotensive) effect of apelin results from the activation of receptors expressed at the surface of endothelial cells. a potent vasodilator, which induces relaxation of the smooth muscle cells of artery wall. Studies performed on mice knocked out for the apelin receptor gene have suggested the existence of a balance between angiotensin II signalling (which increases blood pressure)e and apelin signalling (which lowers it). The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates signal transduction cascades inside the cell, including extracellular signal regulated kinases (ERKs), protein kinase B (PKB, also known as Akt), and p70 s6 kinase phosphorylation, which lead to the proliferation of endothelial cells and the formation of new blood vessels.

The apelin receptor is expressed early during the embryonic development of the heart, where it regulates the migration of cell progenitors fated to differentiate into cardiomyocytes, the contractile cells of the heart. Its expression is also detected in the cardiomyocytes of the adult where apelin behaves as one of the most potent stimulator of cardiac contractility. Aged apelin knockout mice develop progressive impairment of cardiac contractility. Apelin acts as a mediator of the cardiovascular control, including for blood pressure and blood flow. It is one of the most potent stimulators of cardiac contractility yet identified, and plays a role in cardiac tissue remodeling. Apelin levels are increased in left ventricles of patients with chronic heart failure and also in patients with chronic liver disease.

The plasma concentration of apelin is shown to increase during exercise. Paradoxically, exogenous apelin in healthy volunteers reduced VO2 peak (peak oxygen consumption) in an endurance test.

Apelin receptor is also expressed in the neurons of brain areas involved in regulating water and food intake. Apelin injection increases water intake This diuretic effect of apelin in association with its hypotensive effect participates in the homeostatic regulation of body fluid. Apelin is also detected in brain areas which control appetite, but its effects on food intake are very contradictory.

Apelin is expressed and secreted by adipocytes, and its production is increased during adipocyte differentiation and is stimulated by insulin. Most obese people have elevated levels of insulin, which may therefore be the reason why obese people have been reported to also have elevated levels of apelin. unknown cells of endocrine pancreas, colon epithelial cells. In stomach, activation of receptors on enterochromaffine like cells by apelin secreted by parietal cells can inhibit histamine release by enterochromaffine like cells, which in turn decreases acid secretion by parietal cells. This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production.

Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.

Muscle apelin expression decreases with age in rodents and humans. By supplementing aged mice with exogenous apelin, Cedric Dray, Philippe Valet, and their colleagues demonstrated that the peptide was able to promote muscle hypertrophy and consequently induced a gain in strength. They plan to proceed to a Phase 2 trial in older patients who are on ventilators in the intensive care unit (ICU). Such patients suffer both diaphragm atrophy (the weakening of the muscles that allow one to inhale and exhale, which atrophy dangerously due to disuse during time on a ventilator) and critical illness myopathy (the broad weakening of the muscles during extended bed rest). Each of these conditions are associated with poor functional recovery and substantially increased risk of death after illness.