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Article ; Online: Comparison of secreted miRNAs and proteins during proliferation and differentiation of bovine satellite cells in culture implies potential roles in regulating myogenesis.

Nielsen, Søren Drud-Heydary / Sahebekhtiari, Navid / Huang, Ziyu / Young, Jette Feveile / Rasmussen, Martin Krøyer

2023 Volume 894, Page(s) 147979

Abstract: Cultivated meat is an emerging new technology to produce sustainable meat for the future. The common approach for cultivated meat, is the isolation of satellite cells from donor animals, followed by in vitro proliferation and differentiation into ... ...

Abstract	Cultivated meat is an emerging new technology to produce sustainable meat for the future. The common approach for cultivated meat, is the isolation of satellite cells from donor animals, followed by in vitro proliferation and differentiation into primitive muscle fibers. The transformation of satellite cells into myofibers is tightly orchestrated by intra-cellular signaling, while the inter-cellular signaling is less well understood. Thus, the current study was conducted to map the secretion of potential signaling molecules (MicroRNAs and proteins) during proliferation and differentiation. Primary cultures of satellite cells were grown to 50% and 80% confluence, representing the proliferative phase or serum-starved for 1 and 3 days to induce differentiation. Post incubation in FBS-free media, the media were collected and analyzed for miRNA and protein content using gene-arrays and LC-MS/MS, respectively. When comparing the miRNA secretome at 50% and 80% confluence, we observed four differentially expressed miRNA, while only five were differentially expressed when comparing Day 1 to Day 3. A subsequent in silico analysis suggested that pathways of importance for myogenesis, e.g., MAPK and AMPK signaling, could be regulated by the secreted miRNAs. In addition, >300 proteins were secreted, including insulin-like growth factor 1 binding proteins 2, 3, 4, 5 and 6. In conclusion, this study demonstrated differential secretion of several miRNAs and proteins during both proliferation and differentiation of bovine satellite cells in vitro.
MeSH term(s)	Animals ; Cattle ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Muscle, Skeletal/metabolism ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Cell Differentiation/genetics ; Muscle Development/genetics ; Satellite Cells, Skeletal Muscle ; Cell Proliferation/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2023-11-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2023.147979
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Article ; Online: Satellite cells sourced from bull calves and dairy cows differs in proliferative and myogenic capacity - Implications for cultivated meat.

Skrivergaard, Stig / Krøyer Rasmussen, Martin / Sahebekhtiari, Navid / Feveile Young, Jette / Therkildsen, Margrethe

Food research international (Ottawa, Ont.)

2023 Volume 173, Issue Pt 1, Page(s) 113217

Abstract: Cultivated meat produced with primary muscle satellite cells (SCs) will need a continuous supply of isolated cell material from relevant animal donors. Factors such as age, sex, and breed, along with the sustainability and availability of donor animals, ... ...

Abstract	Cultivated meat produced with primary muscle satellite cells (SCs) will need a continuous supply of isolated cell material from relevant animal donors. Factors such as age, sex, and breed, along with the sustainability and availability of donor animals, could determine the most appropriate donor type for an efficient production. In this study, we focus on the proliferation and differentiation of bovine SCs isolated from bull calf and dairy cow muscle samples. The proliferative performance of bull calf SCs was significantly better than SCs from dairy cows, however a dynamic differentiation assay revealed that the degree of fusion and formation of myotubes were similar between donor types. Furthermore, the proliferation of SCs from both donor types was enhanced using an in-house developed serum-free media compared to 10% FBS, which also delayed myogenic differentiation and increased final cell population density. Using gene chip transcriptomics, we identified several differentially expressed genes between the two donor types, which could help explain the observed cellular differences. This data also revealed a high biological variance between the three replicate animals within donor type, which seemed to be decreased when using our in-house serum-free media. With the use of the powerful imaging modalities of Cytation 5, we developed a novel high contrast brightfield-enabled label-free myotube quantification method along with a more efficient end-point fusion analysis using Phalloidin-staining. The results give new insights into the bovine SC biology and potential use of bull calves and dairy cows as relevant donor animals for cultivated beef cell sourcing. The newly developed differentiation assays will further enhance future research within the field of cultivated meat and SC biology.
MeSH term(s)	Female ; Animals ; Cattle ; Male ; Satellite Cells, Skeletal Muscle/metabolism ; Culture Media, Serum-Free/metabolism ; Muscle Fibers, Skeletal ; Cell Differentiation ; Meat
Chemical Substances	Culture Media, Serum-Free
Language	English
Publishing date	2023-07-01
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1111695-x
ISSN	1873-7145 ; 0963-9969
ISSN (online)	1873-7145
ISSN	0963-9969
DOI	10.1016/j.foodres.2023.113217
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Article ; Online: The Mitochondrial Proteomic Signatures of Human Skeletal Muscle Linked to Insulin Resistance.

Kruse, Rikke / Sahebekhtiari, Navid / Højlund, Kurt

International journal of molecular sciences

2020 Volume 21, Issue 15

Abstract: Introduction: Mitochondria are essential in energy metabolism and cellular survival, and there is growing evidence that insulin resistance in chronic metabolic disorders, such as obesity, type 2 diabetes (T2D), and aging, is linked to mitochondrial ... ...

Abstract	Introduction: Mitochondria are essential in energy metabolism and cellular survival, and there is growing evidence that insulin resistance in chronic metabolic disorders, such as obesity, type 2 diabetes (T2D), and aging, is linked to mitochondrial dysfunction in skeletal muscle. Protein profiling by proteomics is a powerful tool to investigate mechanisms underlying complex disorders. However, despite significant advances in proteomics within the past two decades, the technologies have not yet been fully exploited in the field of skeletal muscle proteome. Area covered: Here, we review the currently available studies characterizing the mitochondrial proteome in human skeletal muscle in insulin-resistant conditions, such as obesity, T2D, and aging, as well as exercise-mediated changes in the mitochondrial proteome. Furthermore, we outline technical challenges and limitations and methodological aspects that should be considered when planning future large-scale proteomics studies of mitochondria from human skeletal muscle. Authors' view: At present, most proteomic studies of skeletal muscle or isolated muscle mitochondria have demonstrated a reduced abundance of proteins in several mitochondrial biological processes in obesity, T2D, and aging, whereas the beneficial effects of exercise involve an increased content of muscle proteins involved in mitochondrial metabolism. Powerful mass-spectrometry-based proteomics now provides unprecedented opportunities to perform in-depth proteomics of muscle mitochondria, which in the near future is expected to increase our understanding of the complex molecular mechanisms underlying the link between mitochondrial dysfunction and insulin resistance in chronic metabolic disorders.
MeSH term(s)	Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Humans ; Insulin Resistance ; Mitochondria, Muscle/metabolism ; Mitochondria, Muscle/pathology ; Mitochondrial Proteins/metabolism ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Proteome/metabolism ; Proteomics
Chemical Substances	Mitochondrial Proteins ; Proteome
Language	English
Publishing date	2020-07-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21155374
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Article ; Online: A simple and robust serum-free media for the proliferation of muscle cells.

Skrivergaard, Stig / Young, Jette Feveile / Sahebekhtiari, Navid / Semper, Cameron / Venkatesan, Meenakshi / Savchenko, Alexei / Stogios, Peter J / Therkildsen, Margrethe / Rasmussen, Martin Krøyer

Food research international (Ottawa, Ont.)

2023 Volume 172, Page(s) 113194

Abstract: Cultivated meat production requires an efficient, robust and highly optimized serum-free cell culture media for the needed upscaling of muscle cell expansion. Existing formulations of serum-free media are complex, expensive and have not been optimized ... ...

Abstract	Cultivated meat production requires an efficient, robust and highly optimized serum-free cell culture media for the needed upscaling of muscle cell expansion. Existing formulations of serum-free media are complex, expensive and have not been optimized for muscle cells. Thus, we undertook this work to develop a simple and robust serum-free media for the proliferation of bovine satellite cells (SCs) through Design of Experiment (DOE) and Response Surface Methodology (RSM) using precise and high-throughput image-based cytometry. Proliferative attributes were investigated with transcriptomics and long-term performance was validated using multiple live assays. Here we formulated a media based on three highly optimized components; FGF2 (2 ng/mL), fetuin (600 µg/mL) and BSA (75 µg/mL) which together with an insulin-transferrin-selenium (1x) supplement, sustained the proliferation of bovine SCs, porcine SCs and murine C2C12 muscle cells. Remarkably, cells cultured in our media named Tri-basal 2.0+ performed better than cell cultured in 10% FBS, with respect to proliferation. Hence, the optimized Tri-basal 2.0+ enhanced serum-free cell attachment and long-term proliferation, providing an alternative solution to the use of FBS in the production of cultivated meat.
MeSH term(s)	Animals ; Cattle ; Mice ; Swine ; Culture Media, Serum-Free ; Muscle Cells ; Muscles ; Biological Assay ; Cell Proliferation
Chemical Substances	Culture Media, Serum-Free
Language	English
Publishing date	2023-06-29
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1111695-x
ISSN	1873-7145 ; 0963-9969
ISSN (online)	1873-7145
ISSN	0963-9969
DOI	10.1016/j.foodres.2023.113194
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Article ; Online: Satellite cells sourced from bull calves and dairy cows differs in proliferative and myogenic capacity – Implications for cultivated meat

Skrivergaard, Stig / Krøyer Rasmussen, Martin / Sahebekhtiari, Navid / Feveile Young, Jette / Therkildsen, Margrethe

Food Research International. 2023 Nov., v. 173 p.113217-

2023

Abstract	Cultivated meat produced with primary muscle satellite cells (SCs) will need a continuous supply of isolated cell material from relevant animal donors. Factors such as age, sex, and breed, along with the sustainability and availability of donor animals, could determine the most appropriate donor type for an efficient production. In this study, we focus on the proliferation and differentiation of bovine SCs isolated from bull calf and dairy cow muscle samples. The proliferative performance of bull calf SCs was significantly better than SCs from dairy cows, however a dynamic differentiation assay revealed that the degree of fusion and formation of myotubes were similar between donor types. Furthermore, the proliferation of SCs from both donor types was enhanced using an in-house developed serum-free media compared to 10% FBS, which also delayed myogenic differentiation and increased final cell population density. Using gene chip transcriptomics, we identified several differentially expressed genes between the two donor types, which could help explain the observed cellular differences. This data also revealed a high biological variance between the three replicate animals within donor type, which seemed to be decreased when using our in-house serum-free media. With the use of the powerful imaging modalities of Cytation 5, we developed a novel high contrast brightfield-enabled label-free myotube quantification method along with a more efficient end-point fusion analysis using Phalloidin-staining. The results give new insights into the bovine SC biology and potential use of bull calves and dairy cows as relevant donor animals for cultivated beef cell sourcing. The newly developed differentiation assays will further enhance future research within the field of cultivated meat and SC biology.
Keywords	DNA microarrays ; beef ; calves ; dairy cows ; food research ; gene expression regulation ; muscle development ; muscles ; myotubes ; population density ; transcriptomics ; variance ; Cellular agriculture ; Donor type ; Bovine satellite cell sourcing ; Cell proliferation ; Myogenic differentiation ; Label-free quantification ; Image-based cytometry ; Transcriptomics.
Language	English
Dates of publication	2023-11
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	1111695-x
ISSN	1873-7145 ; 0963-9969
ISSN (online)	1873-7145
ISSN	0963-9969
DOI	10.1016/j.foodres.2023.113217
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Article ; Online: The Mitochondrial Proteomic Signatures of Human Skeletal Muscle Linked to Insulin Resistance

Rikke Kruse / Navid Sahebekhtiari / Kurt Højlund

International Journal of Molecular Sciences, Vol 21, Iss 5374, p

2020 Volume 5374

Abstract	Introduction: Mitochondria are essential in energy metabolism and cellular survival, and there is growing evidence that insulin resistance in chronic metabolic disorders, such as obesity, type 2 diabetes (T2D), and aging, is linked to mitochondrial dysfunction in skeletal muscle. Protein profiling by proteomics is a powerful tool to investigate mechanisms underlying complex disorders. However, despite significant advances in proteomics within the past two decades, the technologies have not yet been fully exploited in the field of skeletal muscle proteome. Area covered: Here, we review the currently available studies characterizing the mitochondrial proteome in human skeletal muscle in insulin-resistant conditions, such as obesity, T2D, and aging, as well as exercise-mediated changes in the mitochondrial proteome. Furthermore, we outline technical challenges and limitations and methodological aspects that should be considered when planning future large-scale proteomics studies of mitochondria from human skeletal muscle. Authors’ view: At present, most proteomic studies of skeletal muscle or isolated muscle mitochondria have demonstrated a reduced abundance of proteins in several mitochondrial biological processes in obesity, T2D, and aging, whereas the beneficial effects of exercise involve an increased content of muscle proteins involved in mitochondrial metabolism. Powerful mass-spectrometry-based proteomics now provides unprecedented opportunities to perform in-depth proteomics of muscle mitochondria, which in the near future is expected to increase our understanding of the complex molecular mechanisms underlying the link between mitochondrial dysfunction and insulin resistance in chronic metabolic disorders.
Keywords	mitochondrial proteomics ; mitochondria ; skeletal muscle ; insulin resistance ; Type 2 diabetes ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: High-throughput proteomics uncovers exercise training and type 2 diabetes-induced changes in human white adipose tissue.

Larsen, Jeppe Kjærgaard / Kruse, Rikke / Sahebekhtiari, Navid / Moreno-Justicia, Roger / Gomez Jorba, Gerard / Petersen, Maria H / de Almeida, Martin E / Ørtenblad, Niels / Deshmukh, Atul S / Højlund, Kurt

Science advances

2023 Volume 9, Issue 48, Page(s) eadi7548

Abstract: White adipose tissue (WAT) is important for metabolic homeostasis. We established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals and patients with type 2 diabetes (T2D) and the response to 8 weeks of high- ... ...

Abstract	White adipose tissue (WAT) is important for metabolic homeostasis. We established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals and patients with type 2 diabetes (T2D) and the response to 8 weeks of high-intensity interval training (HIIT). Using a high-throughput and reproducible mass spectrometry-based proteomics pipeline, we identified 3773 proteins and found that most regulated proteins displayed progression in markers of dysfunctional WAT from lean to obese to T2D individuals and were highly associated with clinical measures such as insulin sensitivity and HbA1c. We propose that these distinct markers could serve as potential clinical biomarkers. HIIT induced only minor changes in the WAT proteome. This included an increase in WAT ferritin levels independent of obesity and T2D, and WAT ferritin levels were strongly correlated with individual insulin sensitivity. Together, we report a proteomic signature of WAT related to obesity and T2D and highlight an unrecognized role of human WAT iron metabolism in exercise training adaptations.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2 ; Insulin Resistance/physiology ; Proteomics ; Adipose Tissue, White/metabolism ; Obesity/metabolism ; Exercise ; Ferritins/metabolism ; Adipose Tissue/metabolism
Chemical Substances	Ferritins (9007-73-2)
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adi7548
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Article ; Online: A simple and robust serum-free media for the proliferation of muscle cells

Skrivergaard, Stig / Young, Jette Feveile / Sahebekhtiari, Navid / Semper, Cameron / Venkatesan, Meenakshi / Savchenko, Alexei / Stogios, Peter J. / Therkildsen, Margrethe / Rasmussen, Martin Krøyer

Food Research International. 2023 Oct., v. 172 p.113194-

2023

Abstract	Cultivated meat production requires an efficient, robust and highly optimized serum-free cell culture media for the needed upscaling of muscle cell expansion. Existing formulations of serum-free media are complex, expensive and have not been optimized for muscle cells. Thus, we undertook this work to develop a simple and robust serum-free media for the proliferation of bovine satellite cells (SCs) through Design of Experiment (DOE) and Response Surface Methodology (RSM) using precise and high-throughput image-based cytometry. Proliferative attributes were investigated with transcriptomics and long-term performance was validated using multiple live assays. Here we formulated a media based on three highly optimized components; FGF2 (2 ng/mL), fetuin (600 µg/mL) and BSA (75 µg/mL) which together with an insulin-transferrin-selenium (1x) supplement, sustained the proliferation of bovine SCs, porcine SCs and murine C2C12 muscle cells. Remarkably, cells cultured in our media named Tri-basal 2.0+ performed better than cell cultured in 10% FBS, with respect to proliferation. Hence, the optimized Tri-basal 2.0+ enhanced serum-free cell attachment and long-term proliferation, providing an alternative solution to the use of FBS in the production of cultivated meat.
Keywords	cattle ; cell culture ; fetuins ; food research ; meat ; meat production ; mice ; muscles ; response surface methodology ; swine ; transcriptomics ; Bovine satellite cells ; Serum-free media optimization ; Cultivated meat ; Image-based cytometry
Language	English
Dates of publication	2023-10
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	1111695-x
ISSN	1873-7145 ; 0963-9969
ISSN (online)	1873-7145
ISSN	0963-9969
DOI	10.1016/j.foodres.2023.113194
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Article ; Online: Deficiency of the mitochondrial sulfide regulator ETHE1 disturbs cell growth, glutathione level and causes proteome alterations outside mitochondria.

Sahebekhtiari, Navid / Fernandez-Guerra, Paula / Nochi, Zahra / Carlsen, Jasper / Bross, Peter / Palmfeldt, Johan

Biochimica et biophysica acta. Molecular basis of disease

2018 Volume 1865, Issue 1, Page(s) 126–135

Abstract: The mitochondrial enzyme ETHE1 is a persulfide dioxygenase essential for cellular sulfide detoxification, and its deficiency causes the severe and complex inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of well-described clinical ... ...

Abstract	The mitochondrial enzyme ETHE1 is a persulfide dioxygenase essential for cellular sulfide detoxification, and its deficiency causes the severe and complex inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of well-described clinical symptoms of the disease, detailed cellular and molecular characterization is still ambiguous. Cellular redox regulation has been described to be influenced in ETHE1 deficient cells, and to clarify this further we applied image cytometry and detected decreased levels of reduced glutathione (GSH) in cultivated EE patient fibroblast cells. Cell growth initiation of the EE patient cells was impaired, whereas cell cycle regulation was not. Furthermore, Seahorse metabolic analyzes revealed decreased extracellular acidification, i. e. decreased lactate formation from glycolysis, in the EE patient cells. TMT-based large-scale proteomics was subsequently performed to broadly elucidate cellular consequences of the ETHE1 deficiency. More than 130 proteins were differentially regulated, of which the majority were non-mitochondrial. The proteomics data revealed a link between ETHE1-deficiency and down-regulation of several ribosomal proteins and LIM domain proteins important for cellular maintenance, and up-regulation of cell surface glycoproteins. Furthermore, several proteins of endoplasmic reticulum (ER) were perturbed including proteins influencing disulfide bond formation (e.g. protein disulfide isomerases and peroxiredoxin 4) and calcium-regulated proteins. The results indicate that decreased level of reduced GSH and alterations in proteins of ribosomes, ER and of cell adhesion lie behind the disrupted cell growth of the EE patient cells.
MeSH term(s)	Brain Diseases, Metabolic, Inborn ; Cell Adhesion ; Cell Cycle/physiology ; Down-Regulation ; Endoplasmic Reticulum/metabolism ; Fibroblasts/metabolism ; Glutathione/metabolism ; Glycolysis ; Glycoproteins/metabolism ; Humans ; LIM Domain Proteins/metabolism ; Lactic Acid/metabolism ; Male ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Nucleocytoplasmic Transport Proteins/metabolism ; Peroxiredoxins/metabolism ; Protein Disulfide-Isomerases/metabolism ; Proteome/metabolism ; Proteomics ; Purpura ; Ribosomal Proteins ; Sulfides/metabolism
Chemical Substances	ETHE1 protein, human ; Glycoproteins ; LIM Domain Proteins ; Mitochondrial Proteins ; Nucleocytoplasmic Transport Proteins ; Proteome ; Ribosomal Proteins ; Sulfides ; Lactic Acid (33X04XA5AT) ; PRDX4 protein, human (EC 1.11.1.15) ; Peroxiredoxins (EC 1.11.1.15) ; Protein Disulfide-Isomerases (EC 5.3.4.1) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2018-11-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2018.10.035
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Article ; Online: Untargeted Metabolomics Analysis Reveals a Link between ETHE1-Mediated Disruptive Redox State and Altered Metabolic Regulation.

Sahebekhtiari, Navid / Nielsen, Camilla Bak / Johannsen, Mogens / Palmfeldt, Johan

Journal of proteome research

2016 Volume 15, Issue 5, Page(s) 1630–1638

Abstract: Defects in the gene encoding the persulfide dioxygenase ETHE1 are known to cause the severe inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of known clinical characteristics, the molecular mechanisms underlying the ETHE1 ... ...

Abstract	Defects in the gene encoding the persulfide dioxygenase ETHE1 are known to cause the severe inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of known clinical characteristics, the molecular mechanisms underlying the ETHE1 deficiency are still obscure. Herein, to further analyze the molecular phenotype of the disease, we applied an untargeted metabolomics approach on cultivated fibroblasts of EE patients for pinpointing alterations in metabolite levels. Metabolites, as direct signatures of biochemical functions, can decipher biochemical pathways involved in the cellular phenotype of patient cells. Using liquid chromatography-mass spectrometry-based untargeted metabolomics, we identified 18 metabolites that have altered levels in fibroblasts from EE patients. Our data demonstrate disrupted redox state in EE patient cells, which is reflected by significantly decreased level of reduced glutathione. Furthermore, the down-regulation of several intermediate metabolites such as the redox cofactors NAD(+) and NADH as well as Krebs cycle intermediates revealed clear alteration in metabolic regulation. Pantothenic acid and several amino acids exhibited decreased levels, whereas the β-citrylglutamate with a putative role in brain development had an increased level in the EE patient cells. These observations indicate the severe impact of ETHE1 deficiency on cellular physiology and redox state, meanwhile suggesting targets for experimental studies on novel treatment options for the devastating metabolic disorder.
MeSH term(s)	Brain Diseases, Metabolic, Inborn/etiology ; Brain Diseases, Metabolic, Inborn/metabolism ; Cells, Cultured ; Chromatography, Liquid ; Down-Regulation ; Fibroblasts/cytology ; Gene Expression Regulation ; Humans ; Metabolism/genetics ; Metabolomics/methods ; Mitochondrial Proteins/deficiency ; Nucleocytoplasmic Transport Proteins/deficiency ; Oxidation-Reduction ; Purpura/etiology ; Purpura/metabolism
Chemical Substances	ETHE1 protein, human ; Mitochondrial Proteins ; Nucleocytoplasmic Transport Proteins
Language	English
Publishing date	2016-05-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.6b00100
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