Involvement of iron depletion in palmitate-induced.
Beta thalassemia is an inherited hemoglobinopathy in which the production of one or both beta globin chains is impaired. The clinical manifestations include hemolytic anemia and impaired iron handling, the severity of which depends on the degree of impairment in beta globin production.
Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes of blood loss include trauma and gastrointestinal bleeding. Causes of decreased production include iron deficiency, vitamin B12 deficiency, thalassemia, and a number of neoplasms of the bone marrow. Causes of increased breakdown include genetic conditions such as sickle cell.
Beta thalassemia major causes major problems and can result in early death. Complications may include delayed growth, bone problems causing facial changes, liver and gall bladder problems, enlarged spleen, enlarged kidneys, diabetes, hypothyroidism, and heart problems.
Pelizaeus-Merzbacher disease is a pediatric leukodystrophy causing oligodendrocyte cell death. Nobuta et al. show that mutations in human PLP1 gene cause iron-induced cell death through lipid peroxidation, abnormal iron metabolism, and hypersensitivity to free iron. Iron chelation rescues cell death, offering a therapeutic direction for a disease without current treatments.
Although red cells are very susceptible to iron-mediated cell injury, they do not bear the assault of reactive oxygen species alone. Damage to cells in other organs accumulates gradually, and eventually becomes clinically significant. Hepatocytes, the primary component cells of the liver, are the major storage site for body iron. With iron overload, these cells are relentlessly bombarded by.
In iron overload, transferrin becomes saturated, and iron that is not bound to transferrin (non-transferrin bound iron, or NTBI) accumulates in the plasma. This free iron is highly reactive and generates harmful free radicals, which can damage lipid membranes, organelles, and DNA, causing cell death and fibrosis. The distribution of NTBI and the pattern of tissue iron uptake determine the.
No one quite understands how this free iron then traverses the interior of the cell, or whether it may be chaperoned by some unknown shepherd, as it makes its way to the mitochondria or other organelles in the cell. This pool of intra-cellular free iron is a prime suspect for where iron might have opportunity to wreak havoc were it to come across a molecule or two of oxygen.