Liepinsh 2021 Free Radic Biol Med
| 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 177:370-80. |
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
On terminology
- For harmonization of terminology on respiratory states and rates, see
- Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. https://doi.org/10.26124/bec:2020-0001.v1
- For harmonization of terminology on respiratory states and rates, see
Labels:
MitoEAGLE terminology
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
