Multimodal Molecular Imaging Demonstrates Myeloperoxidase Regulation of Matrix Metalloproteinase Activity in Neuroinflammation.

Animals Brain / drug effects Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental / chemically induced Female Magnetic Resonance Imaging / methods Matrix Metalloproteinase Inhibitors / pharmacology Matrix Metalloproteinases / metabolism Mice Molecular Imaging / methods Peroxidase / metabolism
Experimental autoimmune encephalomyelitis Fluorescence molecular tomography Magnetic resonance imaging Matrix metalloproteinases Myeloperoxidase Neuroinflammation

Journal

Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963

Informations de publication

Date de publication:
Feb 2019
Historique:
received: 08 09 2017
accepted: 18 05 2018
pubmed: 29 5 2018
medline: 12 7 2019
entrez: 30 5 2018
Statut: ppublish

Résumé

Myeloperoxidase (MPO) has paradoxically been found to be able to both activate matrix metalloproteinases (MMPs) as well as inhibit MMPs. However, these regulatory effects have not yet been observed in vivo, and it is unclear which pathway is relevant in vivo. We aim to track MPO regulation of MMP activity in living animals in neuroinflammation. Mice induced with experimental autoimmune encephalomyelitis (EAE), a mouse model of neuroinflammation and multiple sclerosis, were treated with either the MPO-specific inhibitor 4-aminobenzoic acid hydrazide or saline as control. Mice underwent concurrent magnetic resonance imaging (MRI) with the MPO-specific molecular imaging agent MPO-Gd and fluorescence molecular tomography (FMT) with the MMP-targeting agent MMPsense on day 12 after induction. Biochemical and histopathological correlations were performed. Utilizing concurrent MRI and FMT imaging, we found reduced MMP activity in the brain with MPO inhibition, demonstrating MPO activity positively regulates MMP activity in vivo. In vivo MMPSense activation and MMP-9 activity correlated with MPO-Gd

Identifiants

DOI: 10.1007/s12035-018-1137-2 PMID: 29808380 PMC: PMC6261713
pubmed: 29808380
doi: 10.1007/s12035-018-1137-2
pii: 10.1007/s12035-018-1137-2
pmc: PMC6261713
mid: NIHMS971099
doi:

Substances chimiques

Matrix Metalloproteinase Inhibitors 0
Peroxidase EC 1.11.1.7
Matrix Metalloproteinases EC 3.4.24.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

954-962

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS072167
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS070835
Pays : United States
Organisme : National Institute of Neurological Disorders and Stroke
ID : R01-NS070835
Organisme : National Natural Science Foundation of China
ID : 81771297
Organisme : National Natural Science Foundation of China
ID : 81501116
Organisme : National Institute of Neurological Disorders and Stroke
ID : R01-NS072167

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Auteurs

Yinian Zhang (Y)

Department of Neurosurgery, Institute of Neurology, Lanzhou University Second Hospital, 82 Cuiying Men Road, Lanzhou, 730030, China.
Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

Huateng Dong (H)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.
Department of Pediatric Neurology, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, 730050, China.

Daniel P Seeburg (DP)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.
Neuroradiology Section, Charlotte Radiology, 1701 East Blvd, Charlotte, NC, 28203, USA.

Gregory R Wojtkiewicz (GR)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

Peter Waterman (P)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

Benjamin Pulli (B)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

Reza Forghani (R)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.
Department of Radiology, Jewish General Hospital and McGill University, 3755 Cote Ste-Catherine Road, Montreal, QC, Canada.

Muhammad Ali (M)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

Yoshiko Iwamoto (Y)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

Filip K Swirski (FK)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA.

John W Chen (JW)

Center for Systems Biology and Institute for Innovation in Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 185 Cambridge Street, 5.210 Richard B. Simches Research Building, Boston, MA, 02114, USA. jwchen@mgh.harvard.edu.
ORCID: 0000-0001-7388-9590

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Classifications MeSH

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questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Maladie neurologique auto-immune expérimentale › Encéphalomyélite auto-immune expérimentale › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéases › Inhibiteurs de métalloprotéinases matricielles › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Metalloproteases › Metalloendopeptidases › Matrix metalloproteinases › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Imagerie moléculaire › Multimodal Molecular Imaging Demonstrates...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Peroxidases › Myeloperoxidase › Multimodal Molecular Imaging Demonstrates...