Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

Pedersen, CB, Zolkipli, Z, Vang, S, Palmfeldt, J, Kjeldsen, M, Stenbroen, V, Schmidt, SP, Wanders, RJA, Ruiter, JPN, Wibrand, F, Tein, I & Gregersen, N 2010, 'Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria' Journal of Inherited Metabolic Disease, bind 33, nr. 3, s. 211-22. https://doi.org/10.1007/s10545-010-9086-6

APA

Pedersen, C. B., Zolkipli, Z., Vang, S., Palmfeldt, J., Kjeldsen, M., Stenbroen, V., ... Gregersen, N. (2010). Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria. Journal of Inherited Metabolic Disease, 33(3), 211-22. https://doi.org/10.1007/s10545-010-9086-6

CBE

Pedersen CB, Zolkipli Z, Vang S, Palmfeldt J, Kjeldsen M, Stenbroen V, Schmidt SP, Wanders RJA, Ruiter JPN, Wibrand F, Tein I, Gregersen N. 2010. Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria. Journal of Inherited Metabolic Disease. 33(3):211-22. https://doi.org/10.1007/s10545-010-9086-6

MLA

Vancouver

Author

Pedersen, Christina B ; Zolkipli, Zarazuela ; Vang, Søren ; Palmfeldt, Johan ; Kjeldsen, Margrethe ; Stenbroen, Vibeke ; Schmidt, Stinne P. ; Wanders, Ronald J A ; Ruiter, Jos P N ; Wibrand, Flemming ; Tein, Ingrid ; Gregersen, Niels. / Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria. I: Journal of Inherited Metabolic Disease. 2010 ; Bind 33, Nr. 3. s. 211-22.

Bibtex

@article{3d2c73f213064d93a9042c14a5814f06,
title = "Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria",
abstract = "Mitochondrial dysfunction and oxidative stress are central to the molecular basis of several human diseases associated with neuromuscular disabilities. We hypothesize that mitochondrial dysfunction also contributes to the neuromuscular symptoms observed in patients with ethylmalonic aciduria and homozygosity for ACADS c.625G>A-a common variant of the short-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) enzyme in the mitochondrial fatty acid oxidation pathway. This study sought to identify the specific factors that initiate cell dysfunction in these patients. We investigated fibroblast cultures from 10 patients with neuromuscular disabilities, elevated levels of ethylmalonic acid (EMA) (>50 mmol/mol creatinine), and ACADS c.625G>A homozygosity. Functional analyses, i.e., ACADS gene and protein expression as well as SCAD enzyme activity measurements, were performed together with a global nano liquid chromatography tandem mass spectroscopy (nano-LC-MS/MS)-based screening of the mitochondrial proteome in patient fibroblasts. Moreover, cell viability of patient fibroblasts exposed to menadione-induced oxidative stress was evaluated. Loss of SCAD function was detected in the patient group, most likely due to decreased ACADS gene expression and/or elimination of misfolded SCAD protein. Analysis of the mitochondrial proteome in patient fibroblasts identified a number of differentially expressed protein candidates, including reduced expression of the antioxidant superoxide dismutase 2 (SOD2). Additionally, patient fibroblasts demonstrated significantly higher sensitivity to oxidative stress than control fibroblasts. We propose that reduced mitochondrial antioxidant capacity is a potential risk factor for ACADS c.625G>A-associated ethylmalonic aciduria and that mitochondrial dysfunction contributes to the neurotoxicity observed in patients.",
author = "Pedersen, {Christina B} and Zarazuela Zolkipli and S{\o}ren Vang and Johan Palmfeldt and Margrethe Kjeldsen and Vibeke Stenbroen and Schmidt, {Stinne P.} and Wanders, {Ronald J A} and Ruiter, {Jos P N} and Flemming Wibrand and Ingrid Tein and Niels Gregersen",
year = "2010",
month = "6",
day = "1",
doi = "10.1007/s10545-010-9086-6",
language = "English",
volume = "33",
pages = "211--22",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "3",

}

RIS

TY - JOUR

T1 - Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria

AU - Pedersen, Christina B

AU - Zolkipli, Zarazuela

AU - Vang, Søren

AU - Palmfeldt, Johan

AU - Kjeldsen, Margrethe

AU - Stenbroen, Vibeke

AU - Schmidt, Stinne P.

AU - Wanders, Ronald J A

AU - Ruiter, Jos P N

AU - Wibrand, Flemming

AU - Tein, Ingrid

AU - Gregersen, Niels

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Mitochondrial dysfunction and oxidative stress are central to the molecular basis of several human diseases associated with neuromuscular disabilities. We hypothesize that mitochondrial dysfunction also contributes to the neuromuscular symptoms observed in patients with ethylmalonic aciduria and homozygosity for ACADS c.625G>A-a common variant of the short-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) enzyme in the mitochondrial fatty acid oxidation pathway. This study sought to identify the specific factors that initiate cell dysfunction in these patients. We investigated fibroblast cultures from 10 patients with neuromuscular disabilities, elevated levels of ethylmalonic acid (EMA) (>50 mmol/mol creatinine), and ACADS c.625G>A homozygosity. Functional analyses, i.e., ACADS gene and protein expression as well as SCAD enzyme activity measurements, were performed together with a global nano liquid chromatography tandem mass spectroscopy (nano-LC-MS/MS)-based screening of the mitochondrial proteome in patient fibroblasts. Moreover, cell viability of patient fibroblasts exposed to menadione-induced oxidative stress was evaluated. Loss of SCAD function was detected in the patient group, most likely due to decreased ACADS gene expression and/or elimination of misfolded SCAD protein. Analysis of the mitochondrial proteome in patient fibroblasts identified a number of differentially expressed protein candidates, including reduced expression of the antioxidant superoxide dismutase 2 (SOD2). Additionally, patient fibroblasts demonstrated significantly higher sensitivity to oxidative stress than control fibroblasts. We propose that reduced mitochondrial antioxidant capacity is a potential risk factor for ACADS c.625G>A-associated ethylmalonic aciduria and that mitochondrial dysfunction contributes to the neurotoxicity observed in patients.

AB - Mitochondrial dysfunction and oxidative stress are central to the molecular basis of several human diseases associated with neuromuscular disabilities. We hypothesize that mitochondrial dysfunction also contributes to the neuromuscular symptoms observed in patients with ethylmalonic aciduria and homozygosity for ACADS c.625G>A-a common variant of the short-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) enzyme in the mitochondrial fatty acid oxidation pathway. This study sought to identify the specific factors that initiate cell dysfunction in these patients. We investigated fibroblast cultures from 10 patients with neuromuscular disabilities, elevated levels of ethylmalonic acid (EMA) (>50 mmol/mol creatinine), and ACADS c.625G>A homozygosity. Functional analyses, i.e., ACADS gene and protein expression as well as SCAD enzyme activity measurements, were performed together with a global nano liquid chromatography tandem mass spectroscopy (nano-LC-MS/MS)-based screening of the mitochondrial proteome in patient fibroblasts. Moreover, cell viability of patient fibroblasts exposed to menadione-induced oxidative stress was evaluated. Loss of SCAD function was detected in the patient group, most likely due to decreased ACADS gene expression and/or elimination of misfolded SCAD protein. Analysis of the mitochondrial proteome in patient fibroblasts identified a number of differentially expressed protein candidates, including reduced expression of the antioxidant superoxide dismutase 2 (SOD2). Additionally, patient fibroblasts demonstrated significantly higher sensitivity to oxidative stress than control fibroblasts. We propose that reduced mitochondrial antioxidant capacity is a potential risk factor for ACADS c.625G>A-associated ethylmalonic aciduria and that mitochondrial dysfunction contributes to the neurotoxicity observed in patients.

U2 - 10.1007/s10545-010-9086-6

DO - 10.1007/s10545-010-9086-6

M3 - Journal article

VL - 33

SP - 211

EP - 222

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 3

ER -

ID: 32201868