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Accueil > Equipes de recherche > Chimie Bio-inorganique des Dérivés Soufrés et Pharmacochimie > Thémes de recherche

Redox Homeostasis and Bio(in)organic Chemistry of Reactive Sulfur Species

publié le , mis à jour le

E. Galardon, D. Over, D. Padovani

Collaborators :
Dr. V. Baland (LEM - Université Paris Diderot), Dr. A. Lan and Dr. M. Andriamihaja (AgroParisTech), Dr. F. Bouillaud and Dr. C. Prip-Buus (Institut Cochin - Université Paris Descartes), Dr. X. Norel (Hôpital Bichat - Université Paris Nord), Pr. Dr. P. Hildebrandt (Technische Universität Berlin, Germany), Dr. B. Kloesh (Ludwig Boltzmann Institute for Rheumatology, Balneology and Rehabilitation, Vienna, Austria), Dr S. Sen (Department of Obstetrics and Gynecology, UCLA, USA).

Scientific context

Mammalian cells contain a vast network of redox-based effector signals that regulate critical biological functions to suit the homeostatic metabolic balance and that participate to both our health and the initiation and/or progression of many diseases, such as inflammatory bowel diseases, rheumatoid arthritis, liver diseases, metabolic syndrome, atherosclerosis, etc. Such redox signals include various biosynthetic pathways providing small redox regulatory molecules that may act as “on and off” switches to regulate protein function and redox signaling pathways. The redox effector toolkit, which includes for instance the redox biochemistry of transition metals and reactive sulfur species (RSS) derived from hydrogen sulfide (H2S), is then sourced at multiple spatial and temporal levels to exert diverse functions. It thus appears critical to better understand such redox effector molecules and their biological implications, from redox homeostasis to homeostatic imbalance during physiological or pathological settings. As such, our project relies on a multi-scale and multidisciplinary approach, possible through our collaborative network, to decrypt the intrinsic molecular properties of these redox effector molecules, the redox control of their production and their redox signaling capacity in diverse experimental models and conditions.

  • Intrinsic molecular properties of H2S signaling species (E. Galardon & D. Over)

While general properties regarding H2S reactivity have emerged during this last decade, the fundamental chemistry of its signaling species such as persulfides (RSSH) is currently underdeveloped. This is true, not only because the biological significance of these species has just been acknowledged, but also because persulfides are metastable species that decompose mainly into polysulfides (RS(S)nH, n = 2-6), especially in aqueous buffers. Therefore, establishing reliable chemical tools (design/synthesis of proper model compounds based on the uncommon redox properties of RSSH) to access to persulfides and select relevant model compounds and suitable biological targets for reactivity and structural studies should be critical for this field by gaining a much needed fundamental knowledge on RSS chemical properties. Key words: redox, coordination chemistry, (in)organic chemistry, bio(in)organic chemistry

  • Production and signaling functions of H2S signaling species (E. Galardon & D. Padovani)

In spite of impressive macroscopic observations at the pharmacological level regarding the various signaling properties of H2S and RSS (regulation of the vascular tone, neuromodulation, anti-inflammatory properties), their different levels of integration in biological systems remain obscure. Particularly, the full arrays of H2/RSS effects and signaling pathways are still being elucidated in various systems where H2 displays a wide range of contradictory effects. As a result, we will examine the evidence relating to H2/RSS as modulators of various physiological and pathological functions by using reliable (bio)chemical tools as well as an integrated approach to decipher their mechanisms of action on relevant model compounds and biological targets, and decode their implication and signaling functions in various conditions and systems (molecule, cell, animal). Key words: redox signaling, biochemistry, chemical biology, bio(in)organic chemistry

Recent publications

Reactions of persulfides with the heme cofactor of oxidized myoglobin and microperoxidase 11: reduction or coordination.
Galardon E, Huguet F, Herrero C, Ricoux R, Artaud I, Padovani D.
Dalton Trans. 2017 Jun 28;46(24):7939-7946.
A new link between high homocysteine levels, cancers and neurodegenerative diseases.
Padovani D.
Med Sci (Paris). 2017 May;33(5):494-497.
Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.
Padovani D, Hessani A, Castillo FT, Liot G, Andriamihaja M, Lan A, Pilati C, Blachier F, Sen S, Galardon E, Artaud I.
Nat Commun. 2016 Nov 16;7:13386.
Reverse Regulatory Pathway (H2S / PGE2 / MMP) in Human Aortic Aneurysm and Saphenous Vein Varicosity.
Gomez I, Ozen G, Deschildre C, Amgoud Y, Boubaya L, Gorenne I, Benyahia C, Roger T, Lesèche G, Galardon E, Topal G, Jacob MP, Longrois D, Norel X.
PLoS One. 2016 Jun 30;11(6):e0158421.
Positive feedback during sulfide oxidation fine-tunes cellular affinity for oxygen.
Abou-Hamdan A, Ransy C, Roger T, Guedouari-Bounihi H, Galardon E, Bouillaud F.
Biochim Biophys Acta. 2016 Sep;1857(9):1464-72.
Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation
Wedmann R, Onderka C, Wei S, Szijártó IA, Miljkovic JL, Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, Harrer EG, Harrer T, Ishii I, Gollasch M, Wood ME, Galardon E, Xian M, Whiteman M, Banerjee R, Filipovic M.R
Chem. Sci. . 2016, May 25;7(5):3414-3426.
Reactivity of Persulfides Towards Strained Bicyclo[6.1.0]nonyne Derivatives: Relevance to Chemical Tagging of Proteins.
E. Galardon, D. Padovani
Bioconj. Chem., 2015, 26, 1013-1016
A Persulfide Analog of the Nitrosothiol SNAP: Formation, characterization and Reactivity.
I. Artaud, E. Galardon
ChemBioChem, 2014, 15(16), 2361- 4, also see: Nat. Chem. Biol, 2014, 10,876
Electrophilic Sulfhydration of 8-nitro-cGMP Involves Sulfane Sulfur
V. Terzic, D. Padovani, V. Balland, I. Artaud, E. Galardon
Org. Biomol. Chem, 2014, 12, 5360-5364
New Biologically Active H2S Donors 
T. Roger, F. Raynaud ,  F. Bouillaud, C. Ransy, S. Simonet, C. Crespo,  M.-P. Bourguignon, N. Villeneuve, J.-P. Vilaine, I. Artaud, E. Galardon
ChemBioChem, 2013, 14,2268-2271