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Heme and Iron in oxidative stress and inflammation (HIROS)

Team Gouya / Puy

Department Nephrology, Immunology and Hematology

 

Leader

 

Line-up

 

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.

 

Landmark publications

  • Publication date : 07 February 2019 More

    Erythroid-Progenitor-Targeted Gene Therapy Using Bifunctional TFR1 Ligand-Peptides in Human Erythropoietic Protoporphyria. Am J Hum Genet.

    Autors : Mirmiran Arienne Martin-Schmitt Caroline Lefebvre Thibaud Manceau Hana Daher Raed Oustric V Poli A Lacapère JJ Moulouel Boualem Puy Hervé Peoch'h Katell Lenglet H Simonin S Deybach Jean-Charles Nicolas Gaël Gouya Laurent

  • Publication date : 01 July 2018 More

    Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. J Intern Med.

    Autors : Martin-Schmitt Caroline Lenglet H Yu A Delaby C Benecke A Lefebvre Thibaud Letteron Philippe Paradis Valérie Wahlin S Sandberg S Harper P Sardh E Sandvik AK Hov JR Aarsand AK Chiche L Bazille C Scoazec JY To-Figueras J Carrascal M Abian J Mirmiran Arienne Deybach Jean-Charles Puy Hervé Peoch'h Katell Manceau Hana Gouya Laurent

  • Publication date : 01 April 2018 More

    Involvement of hepcidin in iron metabolism dysregulation in Gaucher disease. Haematologica.

    Autors : Lefebvre Thibaud Reihani N Daher Raed de Villemeur TB Belmatoug N Rose C Colin-Aronovicz Y Puy Hervé Le Van Kim C Franco M

  • Publication date : 19 September 2017 More

    Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Proc Natl Acad Sci U S A

    Autors : Yien YY Ducamp S Van der Vorm LN Kardon JR Manceau Hana Kannengiesser Caroline Bergonia HA Kafina MD Gouya Laurent Baker TA Puy Hervé Phillips JD Nicolas Gaël Paw BH

  • Publication date : 02 March 2017 More

    Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med.

    Autors : Ribeil JA Hacein-Bey-Abina S Payen E Magnani A Semeraro M Magrin E Caccavelli L Neven B Bourget P El Nemer W Bartolucci P Weber L Puy Hervé Meritet JF Grevent D Beuzard Y Chrétien S Lefebvre Thibaud Ross RW Negre O Veres G Sandler L Soni S De Montalembert M Blanche S Leboulch P Cavazzana M

  • Publication date : 01 March 2016 More

    Heterozygous Mutations in BMP6 Pro-peptide Lead to Inappropriate Hepcidin Synthesis and Moderate Iron Overload in Humans. Gastroenterology.

    Autors : Daher Raed Kannengiesser Caroline Houamel D Lefebvre Thibaud Bardou-Jacquet E Ducrot Nicolas De Kerguenec C Jouanolle AM Robreau AM Oudin C Le Gac C Moulouel Boualem Loustaud-Ratti V Bedossa Pierre Valla Dominique Gouya Laurent Beaumont Carole Brissot P Puy Hervé Tchernitchko Dimitri

  • Publication date : 01 March 2016 More

    Hepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coli. J Am Soc Nephrol

    Autors : Houamel D Ducrot Nicolas Lefebvre Thibaud Daher Raed Moulouel Boualem Sari MA Letteron Philippe Lyoumi Said Millot Sarah Tourret J Bouvet O Vaulont S Vandewalle A Denamur E Puy Hervé Beaumont Carole Gouya Laurent

 
 

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Latest Publications

  • Publication date : 23 March 2021 More

    Diverse innate stimuli activate basophils through pathways involving Syk and IκB kinases PNAS

    Autors : Pellefigues Christophe Palak Mehta Sally Chappell Bibek Yumnam Sam Old Mali Camberis Graham Le Gros

  • Publication date : 30 December 2020 More

    Mast Cell Chymase and Kidney Disease International Journal of Molecular Sciences

    Autors : Vibhushan Shamila Bratti Manuela Juan Eduardo Montero-Hernández Alaa El Ghoneimi Benhamou Marc Charles Nicolas Daugas Eric Blank Ulrich

  • Publication date : 21 December 2020 More

    Liver stiffness by transient elastography to detect porto-sinusoidal vascular liver disease with portal hypertension Hepatology

    Autors : Elkrief Laure Marie Lazareth Sylvie Chevret Paradis Valérie Marta Magaz Lorraine Blaise Laura Rubbia-Brandt Moga Lucile Durand François Audrey Payancé Plessier Aurélie Cendrine Chaffaut Valla Dominique Marion Malphettes Alba Diaz Jean-Charles Nault Pierre Nahon Etienne Audureau Vlad Ratziu Castera Laurent Juan-Carlos Garcia Pagan Nathalie Ganne-Carrie Rautou Pierre-Emmanuel ANRS CO12 CirVir group