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An elastase activity reporter for Electronic Paramagnetic Resonance (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a line-shifting nitroxide

hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorJUGNIOT, Natacha
hal.structure.identifierInstitut de Chimie Radicalaire [ICR]
dc.contributor.authorDUTTAGUPTA, Indranil
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorRIVOT, Angelique
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorMASSOT, Philippe
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorCARDIET, Colleen
hal.structure.identifierPhysiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression [PI3]
dc.contributor.authorPIZZOCCARO, Anne
hal.structure.identifierInstitut des Sciences Moléculaires de Marseille [ISM2]
dc.contributor.authorJEAN, Marion
hal.structure.identifierInstitut des Sciences Moléculaires de Marseille [ISM2]
dc.contributor.authorVANTHUYNE, Nicolas
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorFRANCONI, Jean-Michel
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorVOISIN, Pierre
hal.structure.identifierPhysiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression [PI3]
dc.contributor.authorDEVOUASSOUX, Gilles
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorPARZY, Elodie
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorTHIAUDIERE, Eric
hal.structure.identifierInstitut de Chimie Radicalaire [ICR]
hal.structure.identifierVorozhtsov Novosibirsk Institute of Organic Chemistry [RAS, SB, NN ]
dc.contributor.authorMARQUE, Sylvain R.A.
hal.structure.identifierPhysiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression [PI3]
dc.contributor.authorBENTAHER, Abderrazzak
hal.structure.identifierInstitut de Chimie Radicalaire [ICR]
dc.contributor.authorAUDRAN, Gérard
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorMELLET, Philippe
dc.date.accessioned2021-10-07T16:30:02Z
dc.date.available2021-10-07T16:30:02Z
dc.date.issued2018
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112680
dc.description.abstractEnPulmonary inflammatory diseases are a major burden worldwide. They have in common an influx of neutrophils. Neutrophils secrete unchecked proteases at inflammation sites consequently leading to a protease/inhibitor imbalance. Among these proteases, neutrophil elastase is responsible for the degradation of the lung structure via elastin fragmentation. Therefore, monitoring the protease/inhibitor status in lungs non-invasively would be an important diagnostic tool. Herein we present the synthesis of a MeO-Suc-(Ala)(2)-Pro-Val-nitroxide, a line-shifting elastase activity probe suitable for Electron Paramagnetic Resonance spectroscopy (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI). It is a fast and sensitive neutrophil elastase substrate with K-m = 15 +/- 2.9 mu M, k(cat)/K-m = 930,000 s(-1) M-1 and K-m = 25 +/- 5.4 mu M, k(cat)/K-m = 640,000 s(-1) M-1 for the R and S isomers, respectively. These properties are suitable to detect accurately concen trations of neutrophil elastase as low as 1 nM. The substrate was assessed with broncho-alveolar lavages samples derived from a mouse model of Pseudomonas pneumonia. Using EPR spectroscopy we observed a clear-cut difference between wild type animals and animals deficient in neutrophil elastase or deprived of neutrophil Elastase, Cathepsin G and Proteinase 3 or non-infected animals. These results provide new preclinical ex vivo and in vivo diagnostic methods. They can lead to clinical methods to promote in time lung protection.
dc.description.sponsorshipImagerie des maladies inflammatoires pulmonaires via leurs activités enzymatiques à l'aide de L'IRM rehaussée par l'effet Overhauser et des substrats nitroxydes à déplacement de raies - ANR-15-CE18-0012
dc.description.sponsorshipInitiative d'excellence de l'Université de Bordeaux
dc.description.sponsorshipINITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - ANR-11-IDEX-0001
dc.language.isoen
dc.title.enAn elastase activity reporter for Electronic Paramagnetic Resonance (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a line-shifting nitroxide
dc.typeArticle de revue
dc.identifier.doi10.1016/j.freeradbiomed.2018.08.006
dc.subject.halChimie
dc.description.sponsorshipEuropePRES Towards International Gain of Excellence
bordeaux.journalFree Radical Biology and Medicine
bordeaux.page101--112
bordeaux.volume126
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536*
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-02091886
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-02091886v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Free%20Radical%20Biology%20and%20Medicine&rft.date=2018&rft.volume=126&rft.spage=101--112&rft.epage=101--112&rft.au=JUGNIOT,%20Natacha&DUTTAGUPTA,%20Indranil&RIVOT,%20Angelique&MASSOT,%20Philippe&CARDIET,%20Colleen&rft.genre=article


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