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Lipid peroxidation is involved in calcium dependent upregulation of mitochondrial metabolism in skeletal muscle

Al-Menhali, AS; Banu, S; Angelova, PR; Barcaru, A; Horvatovich, P; Abramov, AY; Jaganjac, M; (2020) Lipid peroxidation is involved in calcium dependent upregulation of mitochondrial metabolism in skeletal muscle. Biochimica et Biophysica Acta (BBA) - General Subjects , 1864 (3) , Article 129487. 10.1016/j.bbagen.2019.129487. Green open access

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Abstract

BACKGROUND: Skeletal muscle cells continuously generate reactive oxygen species (ROS). Excessive ROS can affect lipids resulting in lipid peroxidation (LPO). Here we investigated the effects of myotube intracellular calcium-induced signaling eliciting contractions on the LPO induction and the impact of LPO-product 4-hydroxynonenal (4-HNE) on physiology/pathology of myotubes using C2C12 myoblasts. METHODS: C2C12 myoblasts were differentiated into myotubes, stimulated with caffeine and analyzed for the induction of LPO and formation of 4-HNE protein adducts. Further effects of 4-HNE on mitochondrial bioenergetics, NADH level, mitochondrial density and expression of mitochondrial metabolism genes were determined. RESULTS: Short and long-term caffeine stimulation of myotubes promoted superoxide production, LPO and formation of 4-HNE protein adducts. Furthermore, low 4-HNE concentrations had no effect on myotube viability and cellular redox homeostasis, while concentrations from 10 μM and above reduced myotube viability and significantly disrupted homeostasis. A time and dose-dependent 4-HNE effect on superoxide production and mitochondrial NADH-autofluorescence was observed. Finally, 4-HNE had strong impact on maximal respiration, spare respiratory capacity, ATP production, coupling efficiency of mitochondria and mitochondrial density. CONCLUSION: Data presented in this work make evident for the first time that pathological 4-HNE levels elicit damaging effects on skeletal muscle cells while acute exposure to physiological 4-HNE induces transient adaptation. GENERAL SIGNIFICANCE: This work suggests an important role of 4-HNE on the regulation of myotube's mitochondrial metabolism and cellular energy production. It further signifies the importance of skeletal muscle cells hormesis in response to acute stress in order to maintain essential biological functions.

Type: Article
Title: Lipid peroxidation is involved in calcium dependent upregulation of mitochondrial metabolism in skeletal muscle
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbagen.2019.129487
Publisher version: https://doi.org/10.1016/j.bbagen.2019.129487
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: 4-hydroxynonenal, Calcium oscillations, Lipid peroxidation, Mitochondrial metabolism, NADH, Reactive oxygen species
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10087528
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