Harvard
Nochi, Z, Birkler, RID, Fernandez-Guerra, P, Hansen, J
, Wibrand, F, Corydon, TJ, Gregersen, N & Olsen, RKJ 2020, '
Increased antioxidant response in medium-chain acyl-CoA dehydrogenase deficiency: does lipoic acid have a protective role?',
Pediatric Research, bind 88, nr. 4, s. 556-564.
https://doi.org/10.1038/s41390-020-0801-1
APA
Nochi, Z., Birkler, R. I. D., Fernandez-Guerra, P., Hansen, J.
, Wibrand, F., Corydon, T. J., Gregersen, N., & Olsen, R. K. J. (2020).
Increased antioxidant response in medium-chain acyl-CoA dehydrogenase deficiency: does lipoic acid have a protective role? Pediatric Research,
88(4), 556-564.
https://doi.org/10.1038/s41390-020-0801-1
CBE
MLA
Vancouver
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Bibtex
@article{256d65c92a5345c6bef6264973508b86,
title = "Increased antioxidant response in medium-chain acyl-CoA dehydrogenase deficiency: does lipoic acid have a protective role?",
abstract = "BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls.METHODS: Herein we investigate the antioxidant response and mitochondrial function in fibroblasts from MCAD-deficient patients (c.985 A>G/c.985 A>G) and healthy controls.RESULTS: MCAD-deficient fibroblasts showed increased level of mitochondrial superoxide, while lipids were less oxidatively damaged, and higher amount of manganese superoxide dismutase were detected compared to healthy controls, showing forceful antioxidant system in MCADD. We showed increased maximal respiration and reserve capacity in MCAD-deficient fibroblasts compared to controls, indicating more capacity through the tricarboxylic acid (TCA) cycle and subsequently respiratory chain. This led us to study the pyruvate dehydrogenase complex (PDC), the key enzyme in the glycolysis releasing acetyl-CoA to the TCA cycle. MCAD-deficient fibroblasts displayed not only significantly increased PDC but also increased lipoylated PDC protein levels compared to healthy controls.CONCLUSIONS: Based on these findings, we raise the interesting hypothesis that increased PDC-bound lipoic acid, synthesized from accumulated octanoic acid in MCADD, may affect the cellular antioxidant pool in MCADD.",
author = "Zahra Nochi and Birkler, {Rune Isak Dupont} and Paula Fernandez-Guerra and Jakob Hansen and Flemming Wibrand and Corydon, {Thomas Juhl} and Niels Gregersen and Olsen, {Rikke Katrine Jentoft}",
year = "2020",
month = oct,
doi = "10.1038/s41390-020-0801-1",
language = "English",
volume = "88",
pages = "556--564",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Nature Publishing Group",
number = "4",
}
RIS
TY - JOUR
T1 - Increased antioxidant response in medium-chain acyl-CoA dehydrogenase deficiency
T2 - does lipoic acid have a protective role?
AU - Nochi, Zahra
AU - Birkler, Rune Isak Dupont
AU - Fernandez-Guerra, Paula
AU - Hansen, Jakob
AU - Wibrand, Flemming
AU - Corydon, Thomas Juhl
AU - Gregersen, Niels
AU - Olsen, Rikke Katrine Jentoft
PY - 2020/10
Y1 - 2020/10
N2 - BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls.METHODS: Herein we investigate the antioxidant response and mitochondrial function in fibroblasts from MCAD-deficient patients (c.985 A>G/c.985 A>G) and healthy controls.RESULTS: MCAD-deficient fibroblasts showed increased level of mitochondrial superoxide, while lipids were less oxidatively damaged, and higher amount of manganese superoxide dismutase were detected compared to healthy controls, showing forceful antioxidant system in MCADD. We showed increased maximal respiration and reserve capacity in MCAD-deficient fibroblasts compared to controls, indicating more capacity through the tricarboxylic acid (TCA) cycle and subsequently respiratory chain. This led us to study the pyruvate dehydrogenase complex (PDC), the key enzyme in the glycolysis releasing acetyl-CoA to the TCA cycle. MCAD-deficient fibroblasts displayed not only significantly increased PDC but also increased lipoylated PDC protein levels compared to healthy controls.CONCLUSIONS: Based on these findings, we raise the interesting hypothesis that increased PDC-bound lipoic acid, synthesized from accumulated octanoic acid in MCADD, may affect the cellular antioxidant pool in MCADD.
AB - BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls.METHODS: Herein we investigate the antioxidant response and mitochondrial function in fibroblasts from MCAD-deficient patients (c.985 A>G/c.985 A>G) and healthy controls.RESULTS: MCAD-deficient fibroblasts showed increased level of mitochondrial superoxide, while lipids were less oxidatively damaged, and higher amount of manganese superoxide dismutase were detected compared to healthy controls, showing forceful antioxidant system in MCADD. We showed increased maximal respiration and reserve capacity in MCAD-deficient fibroblasts compared to controls, indicating more capacity through the tricarboxylic acid (TCA) cycle and subsequently respiratory chain. This led us to study the pyruvate dehydrogenase complex (PDC), the key enzyme in the glycolysis releasing acetyl-CoA to the TCA cycle. MCAD-deficient fibroblasts displayed not only significantly increased PDC but also increased lipoylated PDC protein levels compared to healthy controls.CONCLUSIONS: Based on these findings, we raise the interesting hypothesis that increased PDC-bound lipoic acid, synthesized from accumulated octanoic acid in MCADD, may affect the cellular antioxidant pool in MCADD.
U2 - 10.1038/s41390-020-0801-1
DO - 10.1038/s41390-020-0801-1
M3 - Journal article
C2 - 32045933
VL - 88
SP - 556
EP - 564
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 4
ER -