Carnosine protects against cerebral ischemic injury by inhibiting matrix-metalloproteinases

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dc.authorid0000-0002-6242-3709
dc.contributor.authorKim, Eun-Hye
dc.contributor.authorKim, Eun-Sun
dc.contributor.authorShin, Donggeun
dc.contributor.authorKim, Donghyun
dc.contributor.authorChoi, Sungbin
dc.contributor.authorShin, Young-Jun
dc.contributor.authorKim, Kyeong-A
dc.contributor.authorNoh, Dabi
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorRajanikant, G. K.
dc.contributor.authorMajid, Arshad
dc.contributor.authorBae, Ok-Nam
dc.date.accessioned2021-08-03T09:53:53Z
dc.date.available2021-08-03T09:53:53Z
dc.date.issued2021
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractStroke is one of the leading causes of death and disability worldwide. However, treatment options for ischemic stroke remain limited. Matrix-metalloproteinases (MMPs) contribute to brain damage during ischemic strokes by disrupting the blood-brain barrier (BBB) and causing brain edemas. Carnosine, an endogenous dipeptide, was found by us and others to be protective against ischemic brain injury. In this study, we investigated whether carnosine influences MMP activity. Brain MMP levels and activity were measured by gelatin zymography after permanent occlusion of the middle cerebral artery (pMCAO) in rats and in vitro enzyme assays. Carnosine significantly reduced infarct volume and edema. Gelatin zymography and in vitro enzyme assays showed that carnosine inhibited brain MMPs. We showed that carnosine inhibited both MMP-2 and MMP-9 activity by chelating zinc. Carnosine also reduced the ischemia-mediated degradation of the tight junction proteins that comprise the BBB. In summary, our findings show that carnosine inhibits MMP activity by chelating zinc, an essential MMP co-factor, resulting in the reduction of edema and brain injury. We believe that our findings shed new light on the neuroprotective mechanism of carnosine against ischemic brain damage.
dc.description.sponsorshipMinistry of Health & Welfare, Republic of Korea ; National Research Foundation of Korea ; Ministry of Science, ICT & Future Planning ; NIHR Sheffield Biomedical Research Centre (BRC)en_US
dc.identifier.citationKim, E.-H., Kim, E.-S., Shin, D., Kim, D., Choi, S., Shin, Y.-J. ... Bae, O.-N. (2021). Carnosine protects against cerebral ischemic injury by inhibiting matrix-metalloproteinases. International Journal of Molecular Sciences, 22(14). https://dx.doi.org/10.3390/ijms22147495
dc.identifier.doi10.3390/ijms22147495
dc.identifier.issn1422-0067
dc.identifier.issue14
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.3390/ijms22147495
dc.identifier.urihttps://hdl.handle.net/20.500.12511/7660
dc.identifier.volume22
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMDPI
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectBrain Edema
dc.subjectCarnosine
dc.subjectIschemic Stroke
dc.subjectMatrix-Metalloproteinases
dc.subjectTight Junction
dc.titleCarnosine protects against cerebral ischemic injury by inhibiting matrix-metalloproteinases
dc.typeArticle

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