Difference between revisions of "Liepinsh 2021 Free Radic Biol Med"

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|year=2021
|year=2021
|journal=Free Radic Biol Med
|journal=Free Radic Biol Med
|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.
|abstract=Increased tissue content of long-chain acylcarnitines may induce mitochondrial and cardiac damage by stimulating ROS production. N<sup>6</sup>-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.
|keywords=Acylcarnitine, Fatty acid metabolism, Gamma-butyrobetaine, Myocardial infarction, PUFA, Trimethyllysine
|keywords=Acylcarnitine, Fatty acid metabolism, Gamma-butyrobetaine, Myocardial infarction, PUFA, Trimethyllysine
|editor=[[Plangger M]]
|editor=[[Plangger M]]
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}}
}}
{{Labeling
{{Labeling
|area=Respiration
|area=Respiration, Genetic knockout;overexpression
|injuries=Ischemia-reperfusion
|organism=Mouse
|tissues=Heart
|preparations=Permeabilized tissue
|couplingstates=LEAK, OXPHOS
|pathways=F, N, S, NS, ROX
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=2021-11
|additional=2021-11
}}
}}

Revision as of 16:03, 10 November 2021

Publications in the MiPMap
Liepinsh E, Kuka J, Vilks K, Svalbe B, Stelfa G, Vilskersts R, Sevostjanovs E, Goldins NR, 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 Radic Biol Med [Epub ahead of print].

» PMID: 34728372 Open Access

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 (2021) Free Radic Biol Med

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. Keywords: Acylcarnitine, Fatty acid metabolism, Gamma-butyrobetaine, Myocardial infarction, PUFA, Trimethyllysine Bioblast editor: Plangger M O2k-Network Lab: LV Riga Makrecka-Kuka M


Labels: MiParea: Respiration, Genetic knockout;overexpression 

Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

2021-11