2022
DOI: 10.3389/fmolb.2022.890653
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Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects

Abstract: Omaveloxolone (RTA408) is a second-generation oleanane triterpenoid Nrf2 inducer with antioxidant and anti-inflammatory properties and was reported to improve mitochondrial bioenergetics. It is currently being tested in medical trials for Friedrich ataxia, a genetic, multi-organ disease involving mitochondrial dysfunction. Thus, omaveloxolone could potentially be beneficial for additional disorders involving mitochondrial dysfunction. To this end, we investigated its effect on primary fibroblasts derived from … Show more

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Cited by 5 publications
(4 citation statements)
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“…Evaluation of the effect of each compound on baseline parameters of cellular and mitochondrial function in microtiter wells, was carried out essentially as we have previously described [9,10] briefly; 3x10 3 cells per well were seeded in triplicates on identical 96-well cell culture plates and incubated for 24 hours at 37°C, 5% CO2. The following day the medium was replaced with fresh GLU medium or restrictive medium, glucose-free DMEM with 5 mM galactose and 5% (FCS) and 2mM Glutamine, (GAL)in the presence of 1μM EQ1 (from a 1mM stock solution in dimethyl sulfoxide (DMSO) or vehicle DMSO.…”
Section: Assessment Of Mitochondrial Function In Microtiter Wellsmentioning
confidence: 99%
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“…Evaluation of the effect of each compound on baseline parameters of cellular and mitochondrial function in microtiter wells, was carried out essentially as we have previously described [9,10] briefly; 3x10 3 cells per well were seeded in triplicates on identical 96-well cell culture plates and incubated for 24 hours at 37°C, 5% CO2. The following day the medium was replaced with fresh GLU medium or restrictive medium, glucose-free DMEM with 5 mM galactose and 5% (FCS) and 2mM Glutamine, (GAL)in the presence of 1μM EQ1 (from a 1mM stock solution in dimethyl sulfoxide (DMSO) or vehicle DMSO.…”
Section: Assessment Of Mitochondrial Function In Microtiter Wellsmentioning
confidence: 99%
“…Oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) were measured essentially as we have previously described [9,10], briefly; fibroblast were seeded in quadruplicates on XF96-well plates in GLU medium, in the absence or presence of EQ1 or vehicle for 72 h. Prior to the measurement, the medium was changed to Seahorse XF unbuffered DMEM medium supplemented with 1 mM pyruvate, 2 mM glutamine and 10 mM glucose and OCR and ECAR were m e a s u r e d b y t h e A g i l e n t S e a h o r s e X F C e l l M i t o Stress Test according to the manufacturer's instructions, using the Seahorse XF Extracellular 96-well Flux Analyzer (Agilent Technologies, Wokingham, UK). The rates were normalized to cell content as measured by MB.…”
Section: Oxygen Consumption and Extracellular Acidification Ratesmentioning
confidence: 99%
“…Omaveloxolone (SKYCLARYS) is the only treatment with FDA approval for use in patients with mitochondrial disease (Friedreich's ataxia). Friedreich's ataxia is a disease characterized by defective Frataxin expression caused by a pathogenic repeat in the Frataxin coding gene, resulting in iron accumulation in mitochondria and increased oxidative stress in cells [167,168]. Omaveloxolone, which is a synthetic derivative of oleanolic acid, binds to Kelch-like ECH-associated protein 1 (Keap1), preventing the degradation of nuclear factor erythroid-2-related factor 2 (Nrf2).…”
Section: Mitochondrial Augmentationmentioning
confidence: 99%
“…Cont.Nrf2 degradation inhibitor; upregulates the expression of antioxidant gene, downregulates the expression of pro-inflammatory genes, and enhances mitochondrial biogenesis[167,168] …”
mentioning
confidence: 99%