Apelin
Encyclopedia
Apelin is a peptide that in humans is encoded by the APLN gene. Apelin is the endogenous ligand
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
.
in the N-terminal region. After translocation into the endoplasmic reticulum
and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and/or the concentrations of those peptides in human plasma has been questioned. Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.
and its activation promotes the formation of new blood vessels (angiogenesis
). The hypotensive effect of apelin results from the activation of receptors expressed at the surface of endothelial cells. This activation induces the release of NO, 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 and apelin signalling, which lowers blood pressure. The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates inside the cell transduction cascades (ERKs, Akt, and p70S6kinase phosphorylation), which lead to the proliferation of endothelial cells and the formation of new blood vessels It is interesting that knockout of apelin gene is associated with a delay in the development of the retinal vasculature.
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
. It is also an adipocyte endocrine secretion, making adipocytic and circulating levels of apelin higher in obesity. Insulin exerts a positive action on adipocyte apelin production. In addition, apelin regulates fluid homeostasis. It is important in the hypothalamic regulation of food and water intake, and pituitary hormone
release.
the secretion of an antidiuretic hormone
, vasopressin
. This diuretic
effect of apelin in association with its hypotensive effect participates in a global manner to the homeostatic regulation of body fluids. Apelin is also detected in brain areas, which control appetite, but its effects on food intake are very contradictory.
enterochromaffine-like cells; 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. In pancreas, apelin inhibits the insulin secretion induced by glucose. This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production. Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels glycemia
.
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
for the G-protein-coupled APJ receptor
Apelin receptor
The apelin receptor is a G protein-coupled receptor which binds apelin....
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
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
, gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, brain, adrenal glands, endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
, and human plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
.
Biosynthesis
Apelin gene encodes a pre-proprotein of 77 amino acids, with a signal peptideSignal peptide
A signal peptide is a short peptide chain that directs the transport of a protein.Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals....
in the N-terminal region. After translocation into the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and/or the concentrations of those peptides in human plasma has been questioned. Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.
Physiological functions
The sites of receptor expression are clearly linked to the different functions played by apelin in the organism.Vascular
Vascular expression of the receptor participates in the control of blood pressureBlood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and its activation promotes the formation of new blood vessels (angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
). The hypotensive effect of apelin results from the activation of receptors expressed at the surface of endothelial cells. This activation induces the release of NO, 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 and apelin signalling, which lowers blood pressure. The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates inside the cell transduction cascades (ERKs, Akt, and p70S6kinase phosphorylation), which lead to the proliferation of endothelial cells and the formation of new blood vessels It is interesting that knockout of apelin gene is associated with a delay in the development of the retinal vasculature.
Cardiac
Apelin receptor is early expressed during the embryonic formation of the heart, where it regulates the migration of cell progenitors fated to differentiate in the contractile cells, the cardiomyocytes. 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 contractilityContractility
Myocardial contractility is the intrinsic ability of the heart to contract independent of preload and afterload. Changes in the ability to produce force during contraction result from different degrees of binding between myosin and actin filaments...
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
Chronic liver disease
Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.- Causes :...
. It is also an adipocyte endocrine secretion, making adipocytic and circulating levels of apelin higher in obesity. Insulin exerts a positive action on adipocyte apelin production. In addition, apelin regulates fluid homeostasis. It is important in the hypothalamic regulation of food and water intake, and pituitary hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
release.
Brain
Apelin receptor is also expressed in the neurons of brain areas involved in water and food intake. Apelin injection increases water intake and apelin decreases in the hypothalamusHypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
the secretion of an antidiuretic hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
, vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
. This diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
effect of apelin in association with its hypotensive effect participates in a global manner to the homeostatic regulation of body fluids. Apelin is also detected in brain areas, which control appetite, but its effects on food intake are very contradictory.
Digestive
Apelin receptor is expressed in several cell types of the gastro-intestinal tract : stomachStomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
enterochromaffine-like cells; unknown cells of endocrine pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
, colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
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. In pancreas, apelin inhibits the insulin secretion induced by glucose. This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production. Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels glycemia
Glycemia
Glycemia means the presence, or the level, of glucose in one's blood. Related words include:* Hyperglycemia, an unusually high concentration of sugar in the blood* Hypoglycemia, an unusually low concentration of sugar in the blood...
.