Hemosiderin is type of Iron storage
Hemosiderin is defined as non-heme, cytoplasmic iron that is insoluble Hemosiderin iron can be used physiologically. A variety of studies converge on the conclusion that hemosiderin is derived from ferritin.
Hemosiderin is an iron-storage complex that is composed of partially digested
ferritin and lysosomes. The breakdown of heme gives rise to biliverdin and
iron. The body then traps the released iron and stores it as hemosiderin in
tissues. Hemosiderin is also generated from the abnormal metabolic pathway of
ferritin.
It
is only found within cells (as opposed to circulating in blood) and appears to
be a complex of ferritin, denatured ferritin and other material. The iron
within deposits of hemosiderin is very poorly available to supply iron when
needed.
Hemosiderin
is most commonly found in macrophages and is especially abundant in situations
following hemorrhage, suggesting that its formation may be related to
phagocytosis of red blood cells and hemoglobin. Hemosiderin can accumulate in
different organs in various diseases.
Iron Regulation & Hemostasis
Iron Regulatory Proteins
A
number of genes associated with the maintenance of iron homeostasis are tightly
regulated in response to the prevailing intracellular iron levels through
post-transcriptional mechanisms that involve interactions between cytosolic
iron regulatory proteins (IRP) and stem-loop structures known as iron
responsive elements (IRE).
HFE
Hereditary
hemochromatosis is a common inborn error of iron metabolism (approximately
1:200 people mainly of northern European decent are affected) that is
characterized by excess iron accumulation and deposition within several
tissues, especially the liver. The most common form of hemochromatosis arises
from an autosomal recessive mutation that leads to the substitution of tyrosine
for cysteine at amino acid 282 (C282Y) of the HFE protein.
Hepcidin
Hepcidin
is central to regulation of iron metabolism. Its effect on a cellular level
involves binding ferroportin, the main iron export protein, resulting in its
internalization and degradation and leading to iron sequestration within
ferroportin-expressing cells.
Hepcidin
deficiency is the cause of iron overload in hereditary hemochromatosis, iron
loading anemias, and hepatitis C. Hepcidin excess is associated with anemia of
inflammation, chronic kidney disease and iron-refractory iron deficiency
anemia.
Dysregulation of
hepcidin production results in a variety of iron disorders. Hepcidin deficiency
is the cause of iron overload in hereditary hemochromatosis, iron-loading
anemias, and hepatitis C. Hepcidin excess is associated with anemia of
inflammation, chronic kidney disease and iron-refractory iron deficiency
anemia.
Iron overload
occurs
by two basic mechanisms: too much is absorbed or too many erythrocytes are
destroyed.
In
the first case, iron in excess of the iron-binding capacity of transferrin is
deposited in parenchymal cells of the liver, heart, and some endocrine tissues.
In
the second case, iron accumulates in the reticuloendothelial macrophages. If
this capacity is exceeded, iron is then stored in the parenchyma. It should be
apparent that the first situation is far more serious and can lead to tissue
damage and fibrosis if not corrected.
Both
types of overloads can be dangerous and lead to damage, but macrophages
function to protect organs as long as possible.
Genuine
iron overload situations arise either through a biologically inappropriate
increase in the absorption of iron despite adequate iron reserves, or
iatrogenically as a result of frequent blood transfusions or inappropriate iron
therapy oral/parenteral.
The
former condition occurs mainly as a result of the disturbance of negative
feedback mechanisms, which in hemochromatosis is manifested as a failure of the
protective mechanism in the mucosa cell due to a defective HFE protein.
Conditions
characterized by ineffective erythropoiesis, such as MDS, thalassemia,
porphyrias, and sideroachrestic as well as hemolytic anemias, presumably lead
to increased absorption of iron as result of hypoxia, despite adequate or even increased
iron reserves.
The iron overload in
these cases is aggravated by the necessary transfusions and by the body's
inability to actively excrete iron. All the mechanisms mentioned ultimately
lead to overloading of the iron stores, and hence redistribution to the
parenchymal cells of many organs, such as the liver, heart, pancreas, and
gonads.
Hemochromatosis represents the most important form of hereditary iron overload. The cys-282-tyr mutation is by far the most. The less common variant is the his-63-asp mutation. The mutations obviously give rise to an abnormal HFE protein in the epithelial cells of the mucosa of the small intestine in the region which is relevant for iron absorption.
Haemochromatosis
is an inherited condition where iron levels in the body slowly build up over
many years. This build-up of iron, known as iron overload, can cause unpleasant
symptoms. If it is not treated, this can damage parts of the body such as the
liver, joints, pancreas and heart.
Iron
overload treatment include:
Dietary
advice (decrease intake or iron, increase intake of natural chelators)
Chelating
therapy – desferrioxamine is an iron-chelating agent that is administered
subcutaneously.
It
is important to start therapy as soon as possible to prevent irreversible organ
damage.
Iron Detoxification
Iron
is required by most organisms, but is potentially toxic due to the low
solubility of the stable oxidation state, Fe(III), and to the tendency to
potentiate the production of reactive oxygen species, ROS.
The
reactivity of iron is counteracted by bacteria with the same strategies
employed by the host, namely by sequestering the metal into ferritin, the
ubiquitous iron storage protein.
Ferritins
are highly conserved, hollow spheres constructed from 24 subunits that are
endowed with ferroxidase activity and can harbor up to 4500 iron atoms as
oxy-hydroxide micelles.
The
release of the metal upon reduction can alter the microorganism-host iron
balance and hence permit bacteria to overcome iron limitation. In bacteria, the
relevance of the Dps (DNA-binding proteins from starved cells) family in iron
storage-detoxification has been recognized recently.
This
latter function allows bacterial pathogens that lack catalase, e.g.
Porphyromonas gingivalis, to survive in an aerobic environment and resist to
peroxide stress.