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dc.contributor.authorManasieva, Vesna
dc.contributor.authorThakur, Shori
dc.contributor.authorLione, Lisa A.
dc.contributor.authorBaydoun, Anwar R.
dc.contributor.authorSkamarauskas, John
dc.contributor.editorKarch, Jason M.
dc.contributor.editorGordon, Joseph W.
dc.date.accessioned2023-09-29T08:30:01Z
dc.date.available2023-09-29T08:30:01Z
dc.date.issued2023-03-03
dc.identifier.citationManasieva , V , Thakur , S , Lione , L A , Baydoun , A R , Skamarauskas , J , Karch , J M (ed.) & Gordon , J W (ed.) 2023 , ' The Impact of Semicarbazide Sensitive Amine Oxidase Activity on Rat Aortic Vascular Smooth Muscle Cells ' , International Journal of Molecular Sciences (IJMS) , vol. 24 , no. 5 , 4946 , pp. 1-19 . https://doi.org/10.3390/ijms24054946
dc.identifier.issn1661-6596
dc.identifier.otherJisc: 1003069
dc.identifier.otherJisc: 1003069
dc.identifier.otherpublisher-id: ijms-24-04946
dc.identifier.urihttp://hdl.handle.net/2299/26786
dc.description© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.description.abstractSemicarbazide-sensitive amine oxidase (SSAO) is both a soluble- and membrane-bound transmembrane protein expressed in the vascular endothelial and in smooth muscle cells. In vascular endothelial cells, SSAO contributes to the development of atherosclerosis by mediating a leukocyte adhesion cascade; however, its contributory role in the development of atherosclerosis in VSMCs has not yet been fully explored. This study investigates SSAO enzymatic activity in VSMCs using methylamine and aminoacetone as model substrates. The study also addresses the mechanism by which SSAO catalytic activity causes vascular damage, and further evaluates the contribution of SSAO in oxidative stress formation in the vascular wall. SSAO demonstrated higher affinity for aminoacetone when compared to methylamine (Km = 12.08 µM vs. 65.35 µM). Aminoacetone- and methylamine-induced VSMCs death at concentrations of 50 & 1000 µM, and their cytotoxic effect, was reversed with 100 µM of the irreversible SSAO inhibitor MDL72527, which completely abolished cell death. Cytotoxic effects were also observed after 24 h of exposure to formaldehyde, methylglyoxal and H 2O 2. Enhanced cytotoxicity was detected after the simultaneous addition of formaldehyde and H 2O 2, as well as methylglyoxal and H 2O 2. The highest ROS production was observed in aminoacetone- and benzylamine-treated cells. MDL72527 abolished ROS in benzylamine-, methylamine- and aminoacetone-treated cells (**** p < 0.0001), while βAPN demonstrated inhibitory potential only in benzylamine-treated cells (* p < 0.05). Treatment with benzylamine, methylamine and aminoacetone reduced the total GSH levels (**** p < 0.0001); the addition of MDL72527 and βAPN failed to reverse this effect. Overall, a cytotoxic consequence of SSAO catalytic activity was observed in cultured VSMCs where SSAO was identified as a key mediator in ROS formation. These findings could potentially associate SSAO activity with the early developing stages of atherosclerosis through oxidative stress formation and vascular damage.en
dc.format.extent19
dc.format.extent5841085
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences (IJMS)
dc.subjectArticle
dc.subjectvascular smooth muscle cells
dc.subjectsemicarbazide-sensitive amine oxidase
dc.subjectmethylamine
dc.subjectaminoacetone
dc.subjectformaldehyde
dc.subjectmethylglyoxal
dc.subjecthydrogen peroxide
dc.subjectreactive oxygen species
dc.subjectHydrogen Peroxide/pharmacology
dc.subjectReactive Oxygen Species/pharmacology
dc.subjectRats
dc.subjectFormaldehyde/pharmacology
dc.subjectMuscle, Smooth, Vascular/metabolism
dc.subjectBenzylamines/pharmacology
dc.subjectAnimals
dc.subjectEndothelial Cells/metabolism
dc.subjectMethylamines/metabolism
dc.subjectAmine Oxidase (Copper-Containing)/metabolism
dc.subjectPyruvaldehyde/pharmacology
dc.subjectMolecular Biology
dc.subjectSpectroscopy
dc.subjectCatalysis
dc.subjectInorganic Chemistry
dc.subjectComputer Science Applications
dc.subjectPhysical and Theoretical Chemistry
dc.subjectOrganic Chemistry
dc.titleThe Impact of Semicarbazide Sensitive Amine Oxidase Activity on Rat Aortic Vascular Smooth Muscle Cellsen
dc.contributor.institutionCentre for Future Societies Research
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.contributor.institutionBasic and Clinical Science Unit
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionTRP Ion channels
dc.contributor.institutionCentre for Research in Mechanisms of Disease and Drug Discovery
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85149891397&partnerID=8YFLogxK
rioxxterms.versionofrecord10.3390/ijms24054946
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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