Erythroferrone
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Erythroferrone
Erythroferrone is a protein hormone encoded in humans by the ''ERFE'' gene. Erythroferrone is produced by erythroblasts, inhibits the production of hepcidin in the liver, and so increases the amount of iron available for hemoglobin synthesis. Skeletal muscle secreted ERFE has been shown to maintain systemic metabolic homeostasis. Discovery It was identified in 2014 in mice where the transcript was found in bone marrow, encoded by the mouse ''Fam132b'' gene. The homologous gene in humans is ''FAM132B'' and the sequence is conserved in other species. The protein is synthesized by erythroblasts and secreted. This sequence had previously been found expressed in mouse skeletal muscle, called myonectin (CTRP15), and linked to lipid homeostasis. Seldin and his colleagues have written: "Myonectin is expressed and secreted predominantly by skeletal muscle.... (Our) results suggest that myonectin is a nutrient-responsive metabolic regulator secreted by skeletal muscle in response to ch ...
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Hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. During conditions in which the hepcidin level is abnormally high, such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red blood cells. When the hepcidin level is abnormally low such as in hemochromatosis, iron overload occurs due to increased ferroportin mediated iron efflux from storage and increased gut iron absorption. Structure Hepcidin exists as a preprohormone (84 amino acids), prohormone (60 amino acids), and hormone (25 amino acids). Twenty- and 22-amino acid metabolites of hepcidin also exist in the urine. Deletion of 5 ''N''-terminal amino acids results in loss of function. The conversion of prohepcidin to hepcidin is mediated by the pr ...
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Iron Metabolism
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically important part of many aspects of human health and disease. Hematologists have been especially interested in systemic iron metabolism because iron is essential for red blood cells, where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of iron overload, such as hereditary hemochromatosis, and iron deficiency, such as iron-deficiency anemia. Importance of iron regulation Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electron transfer. In the ferrous state (Fe2+), iron acts as an electron donor, while in the ferric state (Fe3+) it acts as an acceptor. Thus, iron plays a vital role in the cataly ...
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Iron Metabolism
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically important part of many aspects of human health and disease. Hematologists have been especially interested in systemic iron metabolism because iron is essential for red blood cells, where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of iron overload, such as hereditary hemochromatosis, and iron deficiency, such as iron-deficiency anemia. Importance of iron regulation Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electron transfer. In the ferrous state (Fe2+), iron acts as an electron donor, while in the ferric state (Fe3+) it acts as an acceptor. Thus, iron plays a vital role in the cataly ...
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Erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin.Sherwood, L, Klansman, H, Yancey, P: ''Animal Physiology'', Brooks/Cole, Cengage Learning, 2005. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells (erythrocytes). In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the liver. After seven months, erythropoiesis occurs in the bone marrow. Increased levels of physical ac ...
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Iron Overload
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosis (HH or HHC), a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions. Signs and symptoms Organs most commonly affected by hemochromatosis include the liver, heart, and endocrine glands. Hemochromatosis may present with the following clinical syndromes: * liver: chronic liver disease and cirrhosis of the liver. * heart: heart failure, cardiac arrhythmia. * hormones: diabetes (see below) and hypogonadism (insufficiency of the sex hormone producing glands) which leads to low sex drive and/or loss of fertility in men and loss of menstrual cycle in women. * metabolism: diabetes in people with iron overload occurs as a result of selective iron deposition in islet beta cells in the pancreas lead ...
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Anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Symptoms of anemia depend on how quickly hemoglobin decreases. Additional symptoms may occur depending on the underlying cause. Preoperative anemia can increase the risk of needing a blood transfusion following surgery. Anemia can be temporary or long term and can range from mild to severe. Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes o ...
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Jak2
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R). The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains ( SH2/ SH3) and the presence of up to seven JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of t ...
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Stat5
Signal transducer and activator of transcription 5 (STAT5) refers to two highly related proteins, STAT5A and STAT5B, which are part of the seven-membered STAT family of proteins. Though STAT5A and STAT5B are encoded by separate genes, the proteins are 90% identical at the amino acid level. STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes. Aberrant STAT5 activity has been shown to be closely connected to a wide range of human cancers, and silencing this aberrant activity is an area of active research in medicinal chemistry. Activation and function In order to be functional, STAT5 proteins must first be activated. This activation is carried out by kinases associated with transmembrane receptors: * Ligands binding to these transmembrane receptors on the outside of the cell activate the kinases; * The stimulated kinases add a phosphate group to a specific tyrosine residue on the receptor; * STAT5 then binds to these phosphoryl ...
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Thalassemia
Thalassemias are inherited blood disorders characterized by decreased hemoglobin production. Symptoms depend on the type and can vary from none to severe. Often there is mild to severe anemia (low red blood cells or hemoglobin). Anemia can result in feeling tired and pale skin. There may also be bone problems, an enlarged spleen, yellowish skin, and dark urine. Slow growth may occur in children. Thalassemias are genetic disorders inherited from a person's parents. There are two main types, alpha thalassemia and beta thalassemia. The severity of alpha and beta thalassemia depends on how many of the four genes for alpha globin or two genes for beta globin are missing. Diagnosis is typically by blood tests including a complete blood count, special hemoglobin tests, and genetic tests. Diagnosis may occur before birth through prenatal testing. Treatment depends on the type and severity. Treatment for those with more severe disease often includes regular blood transfusions, iron chel ...
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Erythroblasts
A nucleated red blood cell (NRBC), also known by several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mammals, all of these red blood cells are nucleated. In mammals, NRBCs occur in normal development as precursors to mature red blood cells in erythropoiesis, the process by which the body produces red blood cells. NRBCs are normally found in the bone marrow of humans of all ages and in the blood of fetuses and newborn infants. After infancy, RBCs normally contain a nucleus only during the very early stages of the cell's life, and the nucleus is ejected as a normal part of cellular differentiation before the cell is released into the bloodstream. Thus, if NRBCs are identified on an adult's complete blood count or peripheral blood smear, it suggests that there is a very high demand for the bone marrow to produce RBCs, and immature RBCs are being relea ...
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Anemia Of Chronic Disease
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin production and release from the liver, which in turn shuts down ferroportin, a protein that controls export of iron from the gut and from iron storing cells (e.g. macrophages). As a consequence, circulating iron levels are reduced. Other mechanisms may also play a role, such as reduced erythropoiesis. It is also known as anemia of inflammation, or anemia of inflammatory response. Classification Anemia of chronic disease is usually mild but can be severe. It is usually normocytic, but can be microcytic. The presence of both anemia of chronic disease and dietary iron deficiency results in a more severe anemia. Pathophysiology Anemia is defined by hemoglobin (Hb) concentration * < 13.0 g/dL (130 g/L) in males * < 11.5 g/dL (115 g/L) in females In ...
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Red Blood Cells
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''kytos'' for "hollow vessel", with ''-cyte'' translated as "cell" in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissue (biology), tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or in fish the gills, and release it into tissues while squeezing through the body's capillary, capillaries. The cytoplasm of a red blood cell is rich in hemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells and the blood. Each human red blood cell contains approximately 270 million hemoglobin molecules. The cell membrane is composed of proteins and lipids, and this structure ...
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