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  1. Article: Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis-Nitro-Redox Interconnections.

    Bonetti, Justine / Corti, Alessandro / Lerouge, Lucie / Pompella, Alfonso / Gaucher, Caroline

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 4

    Abstract: Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the ...

    Abstract Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of the local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour. Endothelial dysfunction promotes adhesion to the endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of "foam cells" within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of the underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signalling pathways implicated in plaque formation and of the effects of NO on the molecular steps of the phenotypic switch of macrophages and vSMCs.
    Language English
    Publishing date 2021-03-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10040516
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections

    Bonetti, Justine / Corti, Alessandro / Lerouge, Lucie / Pompella, Alfonso / Gaucher, Caroline

    Antioxidants. 2021 Mar. 26, v. 10, no. 4

    2021  

    Abstract: Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the ...

    Abstract Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of the local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour. Endothelial dysfunction promotes adhesion to the endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of “foam cells” within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of the underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signalling pathways implicated in plaque formation and of the effects of NO on the molecular steps of the phenotypic switch of macrophages and vSMCs.
    Keywords adhesion ; atherosclerosis ; blood pressure ; endothelium ; inflammation ; macrophages ; monocytes ; nitric oxide ; oxidative stress ; phenotype ; plasticity ; smooth muscle ; therapeutics
    Language English
    Dates of publication 2021-0326
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10040516
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos.

    Corti, Alessandro / Bonetti, Justine / Dominici, Silvia / Piaggi, Simona / Fierabracci, Vanna / Foddis, Rudy / Pompella, Alfonso

    Toxicological sciences : an official journal of the Society of Toxicology

    2019  Volume 177, Issue 2, Page(s) 476–482

    Abstract: Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact ... ...

    Abstract Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at subtoxic concentrations (50-250 ng/1000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent pro-oxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.
    MeSH term(s) Asbestos ; Asbestos, Crocidolite/toxicity ; Humans ; Macrophages ; Reactive Oxygen Species ; gamma-Glutamyltransferase
    Chemical Substances Reactive Oxygen Species ; Asbestos, Crocidolite (12001-28-4) ; Asbestos (1332-21-4) ; gamma-Glutamyltransferase (EC 2.3.2.2)
    Language English
    Publishing date 2019-08-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfz175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Glutathione: Antioxidant Properties Dedicated to Nanotechnologies.

    Gaucher, Caroline / Boudier, Ariane / Bonetti, Justine / Clarot, Igor / Leroy, Pierre / Parent, Marianne

    Antioxidants (Basel, Switzerland)

    2018  Volume 7, Issue 5

    Abstract: Which scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary ... ...

    Abstract Which scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary review aims to bring out some lesser-known aspects of GSH, for example, as an emerging tool in nanotechnologies to achieve targeted drug delivery. After recalling the biochemistry of GSH, including its metabolism pathways and redox properties, its involvement in cellular redox homeostasis and signaling is described. Analytical methods for the dosage and localization of GSH or glutathiolated proteins are also covered. Finally, the various therapeutic strategies to replenish GSH stocks are discussed, in parallel with its use as an addressing molecule in drug delivery.
    Language English
    Publishing date 2018-04-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox7050062
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Higher-energy collision-induced dissociation for the quantification by liquid chromatography/tandem ion trap mass spectrometry of nitric oxide metabolites coming from S-nitroso-glutathione in an in vitro model of the intestinal barrier.

    Yu, Haiyan / Bonetti, Justine / Gaucher, Caroline / Fries, Isabelle / Vernex-Loset, Lionel / Leroy, Pierre / Chaimbault, Patrick

    Rapid communications in mass spectrometry : RCM

    2018  Volume 33, Issue 1, Page(s) 1–11

    Abstract: Rationale: The potency of S-nitrosoglutathione (GSNO) as a nitric oxide (NO) donor to treat cardiovascular diseases (CVDs) has been highlighted in numerous studies. In order to study its bioavailability after oral administration, which represents the ... ...

    Abstract Rationale: The potency of S-nitrosoglutathione (GSNO) as a nitric oxide (NO) donor to treat cardiovascular diseases (CVDs) has been highlighted in numerous studies. In order to study its bioavailability after oral administration, which represents the most convenient route for the chronic treatment of CVDs, it is essential to develop an analytical method permitting (i) the simultaneous measurement of GSNO metabolites, i.e. nitrite, S-nitrosothiols (RSNOs) and nitrate and (ii) to distinguish them from other sources (endogenous synthesis and diet).
    Methods: Exogenous GSNO was labeled with
    Results: A LC/ITMS/MS method based on an original transition (m/z 171 to 156) for sodium
    Conclusions: A quantitative LC/ITMS/MS method using HCD was developed for the first time to selectively monitor GS
    MeSH term(s) 2-Naphthylamine/analogs & derivatives ; 2-Naphthylamine/chemistry ; Caco-2 Cells ; Chromatography, Liquid/methods ; Humans ; Intestinal Absorption/drug effects ; Limit of Detection ; Nitric Oxide/analysis ; Nitric Oxide/metabolism ; Nitrites/chemistry ; Reproducibility of Results ; S-Nitrosoglutathione/metabolism ; S-Nitrosoglutathione/pharmacokinetics ; Tandem Mass Spectrometry/instrumentation ; Tandem Mass Spectrometry/methods
    Chemical Substances Nitrites ; 2,3-diaminonaphthalene (2BNZ6BRS87) ; Nitric Oxide (31C4KY9ESH) ; S-Nitrosoglutathione (57564-91-7) ; 2-Naphthylamine (CKR7XL41N4)
    Language English
    Publishing date 2018-09-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 58731-x
    ISSN 1097-0231 ; 0951-4198
    ISSN (online) 1097-0231
    ISSN 0951-4198
    DOI 10.1002/rcm.8287
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Intestinal absorption of S-nitrosothiols: Permeability and transport mechanisms.

    Bonetti, Justine / Zhou, Yi / Parent, Marianne / Clarot, Igor / Yu, Haiyan / Fries-Raeth, Isabelle / Leroy, Pierre / Lartaud, Isabelle / Gaucher, Caroline

    Biochemical pharmacology

    2018  Volume 155, Page(s) 21–31

    Abstract: S-Nitrosothiols, a class of NO donors, demonstrate potential benefits for cardiovascular diseases. Drugs for such chronic diseases require long term administration preferentially through the oral route. However, the absorption of S-nitrosothiols by the ... ...

    Abstract S-Nitrosothiols, a class of NO donors, demonstrate potential benefits for cardiovascular diseases. Drugs for such chronic diseases require long term administration preferentially through the oral route. However, the absorption of S-nitrosothiols by the intestine, which is the first limiting barrier for their vascular bioavailability, is rarely evaluated. Using an in vitro model of intestinal barrier, based on human cells, the present work aimed at elucidating the mechanisms of intestinal transport (passive or active, paracellular or transcellular pathway) and at predicting the absorption site of three S-nitrosothiols: S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-l-cysteine (NACNO) and S-nitroso-N-acetyl-d-penicillamine (SNAP). These S-nitrosothiols include different skeletons carrying the nitroso group, which confer different physico-chemical characteristics and biological activities (antioxidant and anti-inflammatory). According to the values of apparent permeability coefficient, the three S-nitrosothiols belong to the medium class of permeability. The evaluation of the bidirectional apparent permeability demonstrated a passive diffusion of the three S-nitrosothiols. GSNO and NACNO preferentially cross the intestinal barrier though the transcellular pathway, while SNAP followed both the trans- and paracellular pathways. Finally, the permeability of NACNO was favoured at pH 6.4, which is close to the pH of the jejunal part of the intestine. Through this study, we determined the absorption mechanisms of S-nitrosothiols and postulated that they can be administrated through the oral route.
    MeSH term(s) Biological Transport/drug effects ; Biological Transport/physiology ; Caco-2 Cells ; Cell Membrane Permeability/drug effects ; Cell Membrane Permeability/physiology ; Cell Survival/drug effects ; Cell Survival/physiology ; Humans ; Intestinal Absorption/drug effects ; Intestinal Absorption/physiology ; S-Nitrosothiols/metabolism ; S-Nitrosothiols/pharmacology
    Chemical Substances S-Nitrosothiols
    Language English
    Publishing date 2018-06-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2018.06.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Flush with a flash: natural three-component antimicrobial combinations based on

    Alhasan, Rama / Kharma, Ammar / Nasim, Muhammad Jawad / Abdin, Ahmad Yaman / Bonetti, Justine / Giummelly, Philippe / Ejike, Chukwunonso E C C / Leroy, Pierre / Gaucher, Caroline / Jacob, Claus

    MedChemComm

    2018  Volume 9, Issue 12, Page(s) 1994–1999

    Abstract: ... ...

    Abstract S
    Language English
    Publishing date 2018-10-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2545949-1
    ISSN 2040-2511 ; 2040-2503
    ISSN (online) 2040-2511
    ISSN 2040-2503
    DOI 10.1039/c8md00414e
    Database MEDical Literature Analysis and Retrieval System OnLINE

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