title: Activity of matrix metallo proteinases (MMPs) and the tissue inhibitor of MMP (TIMP)-1 in electromagnetic field-exposed THP-1 cells.
abstract: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are the main determinants of tissue remodeling in both physiological and pathological processes. Metabolic processes, which generate oxidants and antioxidants can be influenced by environmental factors such as electromagnetic fields (EMF). We analyzed the effects of EMF on the activity and expression of MMPs in THP-1 cells. Cells were exposed to a 50 Hz, 1 mT EMF for 24 h and incubated with or without LPS. Our data indicate that THP-1 cells exposed to EMF causes a reduction of anti-oxidant enzyme activity and an enhancement of nitrogen intermediates involving the iNOS pathway. We then analyzed the role of nitration of TIMP-1 in increasing the activity of MMPs in EMF exposed cells. Molecular modeling tools were employed to identify the most plausible sites in the active conformation of TIMP-1; at least two protein sites, Y120 and Y38 and/or Y72 were identified. Reactive nitrogen species (RNS) may affect protein targets, such as TIMP-1, which are crucial for the regulation of MMP activities by oxidation of sulfydryl groups, or by nitration of tyrosine residues. These results may suggest a pathway connecting an imbalance of MMPs and their cognate inhibitor TIMP-1.
authors.affiliation: Department of Drug Sciences, University G. d'Annunzio, Chieti, Italy. antoniapatruno@unich.it
authors.forename: Antonia
authors.initials: A
authors.lastname: Patruno
authors.forename: Mirko
authors.initials: M
authors.lastname: Pesce
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marrone
authors.forename: Lorenza
authors.initials: L
authors.lastname: Speranza
authors.forename: Alfredo
authors.initials: A
authors.lastname: Grilli
authors.forename: Maria Anna
authors.initials: MA
authors.lastname: De Lutiis
authors.forename: Mario
authors.initials: M
authors.lastname: Felaco
authors.forename: Marcella
authors.initials: M
authors.lastname: Reale
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D004574:Electromagnetic Fields; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014443:Tyrosine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9