Please use this identifier to cite or link to this item:
10.1016/j.freeradbiomed.2021.10.035
Title: | Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage |
Authors: | Liepinsh, Edgars Kuka, Janis Vilks, Karlis Svalbe, Baiba Stelfa, Gundega Vilskersts, Reinis Sevostjanovs, Eduards Goldins, Niks Ricards Groma, Valerija Grinberga, Solveiga Plaas, Mario Makrecka-Kuka, Marina Dambrova, Maija Rīga Stradiņš University |
Keywords: | 3.1 Basic medicine;1.6 Biological sciences;1.1. Scientific article indexed in Web of Science and/or Scopus database |
Issue Date: | Dec-2021 |
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 |
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. |
Description: | Copyright © 2021. Published by Elsevier Inc. |
DOI: | 10.1016/j.freeradbiomed.2021.10.035 |
ISSN: | 0891-5849 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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Low_cardiac_content_of_long_chain_acylcarnitines.pdf | 4.89 MB | Adobe PDF | View/Open |
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