Please use this identifier to cite or link to this item:
10.1016/j.freeradbiomed.2021.10.035
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DC Field | Value | Language |
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dc.contributor.author | Liepinsh, Edgars | - |
dc.contributor.author | Kuka, Janis | - |
dc.contributor.author | Vilks, Karlis | - |
dc.contributor.author | Svalbe, Baiba | - |
dc.contributor.author | Stelfa, Gundega | - |
dc.contributor.author | Vilskersts, Reinis | - |
dc.contributor.author | Sevostjanovs, Eduards | - |
dc.contributor.author | Goldins, Niks Ricards | - |
dc.contributor.author | Groma, Valerija | - |
dc.contributor.author | Grinberga, Solveiga | - |
dc.contributor.author | Plaas, Mario | - |
dc.contributor.author | Makrecka-Kuka, Marina | - |
dc.contributor.author | Dambrova, Maija | - |
dc.date.accessioned | 2021-11-11T07:45:01Z | - |
dc.date.available | 2021-11-11T07:45:01Z | - |
dc.date.issued | 2021-12 | - |
dc.identifier.citation | Liepinsh , E , Kuka , J , Vilks , K , Svalbe , B , Stelfa , G , Vilskersts , R , Sevostjanovs , E , Goldins , N R , Groma , V , Grinberga , S , Plaas , M , Makrecka-Kuka , M & Dambrova , M 2021 , ' Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage ' , Free Radical Biology and Medicine , vol. 177 , pp. 370-380 . https://doi.org/10.1016/j.freeradbiomed.2021.10.035 | - |
dc.identifier.issn | 0891-5849 | - |
dc.identifier.uri | https://dspace.rsu.lv/jspui/handle/123456789/6815 | - |
dc.description | Copyright © 2021. Published by Elsevier Inc. | - |
dc.description.abstract | Increased tissue content of long-chain acylcarnitines may induce mitochondrial and cardiac damage by stimulating ROS production. N6-trimethyllysine dioxygenase (TMLD) is the first enzyme in the carnitine/acylcarnitine biosynthesis pathway. Inactivation of the TMLHE gene (TMLHE KO) in mice is expected to limit long-chain acylcarnitine synthesis and thus induce a cardio- and mitochondria-protective phenotype. TMLHE gene deletion in male mice lowered acylcarnitine concentrations in blood and cardiac tissues by up to 85% and decreased fatty acid oxidation by 30% but did not affect muscle and heart function in mice. Metabolome profile analysis revealed increased levels of polyunsaturated fatty acids (PUFAs) and a global shift in fatty acid content from saturated to unsaturated lipids. In the risk area of ischemic hearts in TMLHE KO mouse, the OXPHOS-dependent respiration rate and OXPHOS coupling efficiency were fully preserved. Additionally, the decreased long-chain acylcarnitine synthesis rate in TMLHE KO mice prevented ischaemia-reperfusion-induced ROS production in cardiac mitochondria. This was associated with a 39% smaller infarct size in the TMLHE KO mice. The arrest of the acylcarnitine biosynthesis pathway in TMLHE KO mice prevents ischaemia-reperfusion-induced damage in cardiac mitochondria and decreases infarct size. These results confirm that the decreased accumulation of ROS-increasing fatty acid metabolism intermediates prevents mitochondrial and cardiac damage during ischaemia-reperfusion. | en |
dc.format.extent | 5009208 | - |
dc.language.iso | eng | - |
dc.relation.ispartof | Free Radical Biology and Medicine | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | 3.1 Basic medicine | - |
dc.subject | 1.6 Biological sciences | - |
dc.subject | 1.1. Scientific article indexed in Web of Science and/or Scopus database | - |
dc.title | Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage | en |
dc.type | /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article | - |
dc.identifier.doi | 10.1016/j.freeradbiomed.2021.10.035 | - |
dc.contributor.institution | Rīga Stradiņš University | - |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85118848478&partnerID=8YFLogxK | - |
dc.description.status | Peer reviewed | - |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
Files in This Item:
File | Size | Format | |
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Low_cardiac_content_of_long_chain_acylcarnitines.pdf | 4.89 MB | Adobe PDF | View/Open |
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