Team leader

Presentation

 

The iron that is present in all the cells of the body, is necessary for life. It is used primarily to provide oxygen transport, electron transfer reactions, or DNA synthesis. However, the excess iron represents a real threat for the cell since it is able to generate free radicals (or “reactive oxygen species” (ROS)) during the Fenton reaction (chemical reaction, which produces from iron and oxygenated water of the hydroxyl radical: H2O2 + Fe2+®OH + OH· + Fe3+).

Iron is used mainly to produce heme, the prosthetic group of hemoproteins such as hemoglobin, myoglobin, cytochrome P450, …. In plasma, iron is bound to transferrin and its renewal is ensured on the one hand by intestinal absorption from the diet at the duodenal enterocytes (about 2 mg of iron absorbed per day) and by tissue macrophages recycling of hemoglobin, following phagocytosis of senescent red blood cells (approximately 25 mg / day). Both intestinal absorption of iron and recycling of heme-iron are controlled by hepcidin, a small peptide synthesized and secreted by the liver.

The expression of hepcidin is upregulated by iron overload and inflammation, but repressed by iron deficiency and by all the situations that stimulate erythropoiesis. The newly available hepcidin assay provides a new tool for optimizing intravenous iron treatment of anemia, particularly in inflammatory conditions.

Hepcidin is also expressed in many other organs, albeit at a much lower level. It could play a role of anti-bacterial defense.

The main pathologies linked to iron and heme metabolism disorders are: iron deficiency, hypochromic genetic microcytic anemia (sideroblastic or not), anemia of inflammation, iron overload (genetic and secondary hemochromatosis, inflammatory states), and porphyria.

Our projects allow to explore:

  • Axis 1. iron metabolism and hepcidin in the control of bacterial infections and in inflammatory conditions (deciphering the role of extrahepatic hepcidin versus hepatic hepcidin).
  • Axis 2.Pathophysiology and treatment of acute Intermittent Porphyria (AIP): oxidative stress and inflammation in resistance to heme treatment.
  • Axis 3.iron, heme and erythropoiesis in erythropoietic porphyria and genetic microcytic anemias related to abnormalities of iron metabolism.

The HIROS team brings together doctors and researchers specialized in the metabolism of heme and iron and related pathologies. Our projects are dictated in large part by our connections to the French Porphyries Center (Louis Mourier Hospital), the molecular diagnostic activity of rare microcytic anemias APHP HUPNVS (Bichat Hospital), the « Epnet » network, the laboratory of excellence GRex, and DHU Unity.

L’équipe HIROS est responsable de la plateforme Biochimie & Métabolisme (http://www.cri1149.fr/v3/) et du dosage de l’hepcidine par spectroscopie de masse LCMSMS.