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Iron regulation by hepatocytes and free radicals.

Takami T, Sakaida I - J Clin Biochem Nutr (2011)

Bottom Line: Produced free radicals attack cellular proteins, lipids and nucleic acid.Several detoxification system and anti-oxidant defense mechanisms exist to prevent cellular damage by free radicals.Excessive free radicals can lead to hepatocellular damage, liver fibrosis, and hepatocarcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Laboratory, Yamaguchi University Hospital, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.

ABSTRACT
Iron is an essential metallic microelement for life. However, iron overload is toxic. The liver serves an important role as a storehouse for iron in the body. About 20-25 mg of iron is required each day for hemoglobin synthesis. To maintain iron homeostasis, transferrin and transferrin receptors are primarily involved in the uptake of iron into hepatocytes, ferritin in its storage, and ferroportin in its export. Moreover, hepcidin controls ferroportin and plays a central role in the iron metabolism. Excess "free" reactive iron produces damaging free radicals via Fenton or Harber-Weiss reactions. Produced free radicals attack cellular proteins, lipids and nucleic acid. Several detoxification system and anti-oxidant defense mechanisms exist to prevent cellular damage by free radicals. Excessive free radicals can lead to hepatocellular damage, liver fibrosis, and hepatocarcinogenesis.

No MeSH data available.


Related in: MedlinePlus

The IRP-IRE regulatory system. A: Regulation of TfR1; at the high level of iron, the IRPs binding with multiple IREs in the 3' UTRs of TfR1 mRNA promotes TfR1 mRNA’s translation via mRNA stabilization. B: Regulation of ferritin; the IRP binding with the single IRE in the 5' UTRs of ferritin mRNA blocks the translation of ferritin message. In iron overload, the IRP contained the Fe-S cluster cannot bind with the IRE in the 5' UTRs of ferritin mRNA, resulting in the increased translation of ferritin message.
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Figure 1: The IRP-IRE regulatory system. A: Regulation of TfR1; at the high level of iron, the IRPs binding with multiple IREs in the 3' UTRs of TfR1 mRNA promotes TfR1 mRNA’s translation via mRNA stabilization. B: Regulation of ferritin; the IRP binding with the single IRE in the 5' UTRs of ferritin mRNA blocks the translation of ferritin message. In iron overload, the IRP contained the Fe-S cluster cannot bind with the IRE in the 5' UTRs of ferritin mRNA, resulting in the increased translation of ferritin message.

Mentions: Fe2-Tf binds with TfR1 on the cell membrane surface and forms a complex that is then taken up into hepatocytes by endocytosis.(14) Mice lacking TfR1 die during mid-gestation from reduction in erythrocyte sell size and hemoglobin content, an indication of its physiological essentiality.(15) TfR1 expression is controlled by the excess or deficiency of iron within cells, and is regulated by interactions between trans-acting iron regulatory proteins (IRP1 and IRP2) and multiple iron-responsive elements (IREs) present in the 3'-untranslated regions (UTRs) of TfR1 mRNA (The IRP-IRE regulatory system).(16–18) When there is insufficient iron, IRP binds with multiple IREs in the 3' UTR of TfR1 mRNA, and TfR1 protein levels increase via stabilization of the mRNA. In a state of excess iron, on the other hand, IRP is released from multiple IREs.(19) Thus, IRP acts as a sensor protein for intracellular iron and regulates the expression of IRE genes (Fig. 1A).


Iron regulation by hepatocytes and free radicals.

Takami T, Sakaida I - J Clin Biochem Nutr (2011)

The IRP-IRE regulatory system. A: Regulation of TfR1; at the high level of iron, the IRPs binding with multiple IREs in the 3' UTRs of TfR1 mRNA promotes TfR1 mRNA’s translation via mRNA stabilization. B: Regulation of ferritin; the IRP binding with the single IRE in the 5' UTRs of ferritin mRNA blocks the translation of ferritin message. In iron overload, the IRP contained the Fe-S cluster cannot bind with the IRE in the 5' UTRs of ferritin mRNA, resulting in the increased translation of ferritin message.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045680&req=5

Figure 1: The IRP-IRE regulatory system. A: Regulation of TfR1; at the high level of iron, the IRPs binding with multiple IREs in the 3' UTRs of TfR1 mRNA promotes TfR1 mRNA’s translation via mRNA stabilization. B: Regulation of ferritin; the IRP binding with the single IRE in the 5' UTRs of ferritin mRNA blocks the translation of ferritin message. In iron overload, the IRP contained the Fe-S cluster cannot bind with the IRE in the 5' UTRs of ferritin mRNA, resulting in the increased translation of ferritin message.
Mentions: Fe2-Tf binds with TfR1 on the cell membrane surface and forms a complex that is then taken up into hepatocytes by endocytosis.(14) Mice lacking TfR1 die during mid-gestation from reduction in erythrocyte sell size and hemoglobin content, an indication of its physiological essentiality.(15) TfR1 expression is controlled by the excess or deficiency of iron within cells, and is regulated by interactions between trans-acting iron regulatory proteins (IRP1 and IRP2) and multiple iron-responsive elements (IREs) present in the 3'-untranslated regions (UTRs) of TfR1 mRNA (The IRP-IRE regulatory system).(16–18) When there is insufficient iron, IRP binds with multiple IREs in the 3' UTR of TfR1 mRNA, and TfR1 protein levels increase via stabilization of the mRNA. In a state of excess iron, on the other hand, IRP is released from multiple IREs.(19) Thus, IRP acts as a sensor protein for intracellular iron and regulates the expression of IRE genes (Fig. 1A).

Bottom Line: Produced free radicals attack cellular proteins, lipids and nucleic acid.Several detoxification system and anti-oxidant defense mechanisms exist to prevent cellular damage by free radicals.Excessive free radicals can lead to hepatocellular damage, liver fibrosis, and hepatocarcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Laboratory, Yamaguchi University Hospital, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.

ABSTRACT
Iron is an essential metallic microelement for life. However, iron overload is toxic. The liver serves an important role as a storehouse for iron in the body. About 20-25 mg of iron is required each day for hemoglobin synthesis. To maintain iron homeostasis, transferrin and transferrin receptors are primarily involved in the uptake of iron into hepatocytes, ferritin in its storage, and ferroportin in its export. Moreover, hepcidin controls ferroportin and plays a central role in the iron metabolism. Excess "free" reactive iron produces damaging free radicals via Fenton or Harber-Weiss reactions. Produced free radicals attack cellular proteins, lipids and nucleic acid. Several detoxification system and anti-oxidant defense mechanisms exist to prevent cellular damage by free radicals. Excessive free radicals can lead to hepatocellular damage, liver fibrosis, and hepatocarcinogenesis.

No MeSH data available.


Related in: MedlinePlus