uu.seUppsala universitets publikationer
Ändra sökning
Länk till posten
Permanent länk

Direktlänk
BETA
Arvidsson, Torbjörn
Alternativa namn
Publikationer (10 of 28) Visa alla publikationer
Erngren, I., Haglöf, J., Engskog, M. K., Nestor, M., Hedeland, M., Arvidsson, T. & Pettersson, C. (2019). Adduct formation in electrospray ionisation-mass spectrometry with hydrophilic interaction liquid chromatography is strongly affected by the inorganic ion concentration of the samples. Journal of Chromatography A, 1600, 174-182
Öppna denna publikation i ny flik eller fönster >>Adduct formation in electrospray ionisation-mass spectrometry with hydrophilic interaction liquid chromatography is strongly affected by the inorganic ion concentration of the samples
Visa övriga...
2019 (Engelska)Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1600, s. 174-182Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Hydrophilic interaction liquid chromatography (HILIC)/electrospray ionisation-mass spectrometry (ESI-MS) has gained interest for the analysis of polar analytes in bioanalytical applications in recent years. However, ESI-MS is prone to adduct formation of analytes. In contrast to reversed phase chromatography, small inorganic ions have retention in HILIC, i.e. analytes and inorganic ions may co-elute, which could influence the adduct formation. In the present paper, it was demonstrated that the co-elution of sodium ions or potassium ions and analytes in HILIC/ESI-MS affect the adduct formation and that different concentrations of sodium ions and potassium ions in biological samples could have an impact on the quantitative response of the respective adducts as well as the quantitative response of the protonated adduct. The co-elution also lead to cluster formation of analytes and sodium formate or potassium formate, causing extremely complicated spectra. In analytical applications using HILIC/ESI-MS where internal standards are rarely used or not properly matched, great care needs to be taken to ensure minimal variation of inorganic ion concentration between samples. Moreover, the use of alkali metal ion adducts as quantitative target ions in relative quantitative applications should be made with caution if proper internal standards are not used.

Ort, förlag, år, upplaga, sidor
ELSEVIER SCIENCE BV, 2019
Nyckelord
Adduct formation, Hydrophilic interaction liquid chromatography, Mass spectrometry, Screening, Metabolomics, Cluster formation
Nationell ämneskategori
Analytisk kemi
Identifikatorer
urn:nbn:se:uu:diva-390383 (URN)10.1016/j.chroma.2019.04.049 (DOI)000472687800021 ()31047661 (PubMedID)
Tillgänglig från: 2019-08-12 Skapad: 2019-08-12 Senast uppdaterad: 2019-08-12Bibliografiskt granskad
Haglind, A., Hedeland, M., Arvidsson, T. & Pettersson, C. E. (2018). Major signal suppression from metal ion clusters in SFC/ESI-MS: Cause and Effects. Journal of chromatography. B, 1084, 96-105
Öppna denna publikation i ny flik eller fönster >>Major signal suppression from metal ion clusters in SFC/ESI-MS: Cause and Effects
2018 (Engelska)Ingår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 1084, s. 96-105Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The widening application area of SFC-MS with polar analytes and water-containing samples facilitates the use of quick and simple sample preparation techniques such as “dilute and shoot” and protein precipitation. This has also introduced new polar interfering components such as alkali metal ions naturally abundant in e.g. blood plasma and urine, which have shown to be retained using screening conditions in SFC/ESI-TOF-MS and causing areas of major ion suppression. Analytes co-eluting with these clusters will have a decreased signal intensity, which might have a major effect on both quantification and identification. When investigating the composition of the alkali metal clusters using accurate mass and isotopic pattern, it could be concluded that they were previously not described in the literature. Using NaCl and KCl standards and different chromatographic conditions, varying e.g. column and modifier, the clusters proved to be formed from the alkali metal ions in combination with the alcohol modifier and make-up solvent. Their compositions were [(XOCH3)n+X]+, [(XOH)n+X]+, [(X2CO3)n+X]+ and [(XOOCOCH3)n+X]+ for X= Na+ or K+ in ESI+. In ESI-, the clusters depended more on modifier, with [(XCl)n+Cl]- and [(XOCH3)n+OCH3]- mainly formed in pure methanol and [(XOOCH)n+OOCH]- when 20 mM NH4Fa was added.

To prevent the formation of the clusters by avoiding methanol as modifier might be difficult, as this is a widely used modifier providing good solubility when analyzing polar compounds in SFC. A sample preparation with e.g. LLE would remove the alkali ions, however also introducing a time consuming and discriminating step into the method. Since the alkali metal ions were retained and affected by chromatographic adjustments as e.g. mobile phase modifications, a way to avoid them could therefore be chromatographic tuning, when analyzing samples containing them.

Nyckelord
SFC-MS, matrix effect, alkali metal, ion cluster, Supercritical fluid chromatography, ESI
Nationell ämneskategori
Analytisk kemi
Forskningsämne
Analytisk farmaceutisk kemi
Identifikatorer
urn:nbn:se:uu:diva-345978 (URN)10.1016/j.jchromb.2018.03.024 (DOI)000430524400012 ()29579734 (PubMedID)
Tillgänglig från: 2018-03-13 Skapad: 2018-03-13 Senast uppdaterad: 2018-06-26Bibliografiskt granskad
Elmsjö, A., Haglöf, J., Engskog, M. K., Erngren, I., Nestor, M., Arvidsson, T. & Pettersson, C. (2018). Method selectivity evaluation using the co-feature ratio in LC/MS metabolomics: Comparison of HILIC stationary phase performance for the analysis of plasma, urine and cell extracts.. Journal of Chromatography A, 1568, 49-56
Öppna denna publikation i ny flik eller fönster >>Method selectivity evaluation using the co-feature ratio in LC/MS metabolomics: Comparison of HILIC stationary phase performance for the analysis of plasma, urine and cell extracts.
Visa övriga...
2018 (Engelska)Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1568, s. 49-56Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Evaluation of the chromatographic separation in metabolomics studies has primarily been done using preselected sets of standards or by counting the number of detected features. An alternative approach is to calculate each feature's co-feature ratio, which is a combined selectivity measurement for the separation (i.e. extent of co-elution) and the MS-signal (i.e. adduct formation and in-source fragmentation). The aim of this study was to demonstrate how the selectivity of different HILIC stationary phases can be evaluated using the co-feature ratio approach. The study was based on three sample types; plasma, urine and cell extracts. Samples were analyzed on an UHPLC-ESI-Q-ToF system using an amide, a bare silica and a sulfobetaine stationary phase. For each feature, a co-feature ratio was calculated and used for multivariate analysis of the selectivity differences between the three stationary phases. Unsupervised PCA models indicated that the co-feature ratios were highly dependent on type of stationary phase. For several metabolites a 15-30 fold difference in the co-feature ratio were observed between the stationary phases. Observed selectivity differences related primarily to the retention patterns of unwanted matrix components such as inorganic salts (detected as salt clusters), glycerophospholipids, and polyethylene glycols. These matrix components affected the signal intensity of co-eluting metabolites by interfering with the ionization efficiency and/or their adduct formation. Furthermore, the retention pattern of these matrix components had huge influence on the number of detected features. The co-feature ratio approach has successfully been applied for evaluation of the selectivity performance of three HILIC stationary phases. The co-feature ratio could therefore be used in metabolomics for developing selective methods fit for their purpose, thereby avoiding generic analytical approaches, which are often biased, as type and amount of interfering matrix components are metabolome dependent.

Nyckelord
Co-feature ratio (CFR), Hydrophilic interaction chromatography, Mass spectrometry, Metabolomics, Salt clusters
Nationell ämneskategori
Analytisk kemi Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-364208 (URN)10.1016/j.chroma.2018.05.007 (DOI)000443669600006 ()29789170 (PubMedID)
Tillgänglig från: 2018-10-24 Skapad: 2018-10-24 Senast uppdaterad: 2018-10-29Bibliografiskt granskad
Svan, A., Hedeland, M., Arvidsson, T. & Pettersson, C. (2018). The differences in matrix effect between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS. Analytica Chimica Acta, 1000, 163-171
Öppna denna publikation i ny flik eller fönster >>The differences in matrix effect between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS
2018 (Engelska)Ingår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1000, s. 163-171Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

For many sample matrices, matrix effects are a troublesome phenomenon using the electrospray ionization source. The increasing use of supercritical fluid chromatography with CO2 in combination with the electrospray ionization source for MS detection is therefore raising questions: is the matrix effect behaving differently using SFC in comparison with reversed phase LC? This was investigated using urine, plasma, influent-and effluent-wastewater as sample matrices. The matrix effect was evaluated using the post-extraction addition method and through post-column infusions. Matrix effect profiles generated from the post-column infusions in combination with time of flight-MS detection provided the most valuable information for the study. The combination of both qualitative and semi-quantitative information with the ability to use HRMS-data for identifying interfering compounds from the same experiment was very useful, and has to the authors' knowledge not been used this way before. The results showed that both LC and SFC are affected by matrix effects, however differently depending on sample matrix. Generally, both suppressions and enhancements were seen, with a higher amount of enhancements for LC, where 65% of all compounds and all sample matrices were enhanced, compared to only 7% for SFC. Several interferences were tentatively identified, with phospholipids, creatinine, and metal ion clusters as examples of important interferences, with different impact depending on chromatographic technique. SFC needs a different strategy for limiting matrix interferences, owing to its almost reverse retention order compared to RPLC.

Ort, förlag, år, upplaga, sidor
ELSEVIER SCIENCE BV, 2018
Nyckelord
Matrix effects, Supercritical fluid chromatography, Electrospray ionization, Liquid chromatography, Ion enhancement, Ion suppression
Nationell ämneskategori
Analytisk kemi
Identifikatorer
urn:nbn:se:uu:diva-338947 (URN)10.1016/j.aca.2017.10.014 (DOI)000418832900015 ()29289305 (PubMedID)
Tillgänglig från: 2018-01-25 Skapad: 2018-01-25 Senast uppdaterad: 2018-03-15Bibliografiskt granskad
Pierre, P. V., Haglöf, J., Linder, B., Engskog, M. K., Arvidsson, T., Pettersson, C., . . . Laurell, G. (2017). Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity. Acta Oto-Laryngologica, 137(10), 1024-1030
Öppna denna publikation i ny flik eller fönster >>Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity
Visa övriga...
2017 (Engelska)Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 137, nr 10, s. 1024-1030Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo.

AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity.

MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7). Ototoxicity was evaluated by ABR (3-30 kHz) before and 4 d after drug treatment, and by assessment of hair cell loss. A blood sample was drawn before and 4 d after drug treatment and the polar metabolome in serum was analyzed using LC-MS.

RESULTS: Cisplatin-treatment caused significant threshold elevations and outer hair cell (OHC) loss in both groups. The ototoxicity was generally lower in group STS, but a significant difference was reached only at 30 kHz (p = .007). Cisplatin treatment altered the metabolite profile significantly and similarly in both groups. A significant inverse correlation was found between L-acetylcarnitine, N-acetylneuraminic acid, ceramide, and cysteinylserine and high frequency hearing loss in group NaCl. The implication of these correlations should be explored in targeted studies.

Nyckelord
ABR, cisplatin, hair cell, metabolite profiling, ototoxicity, sodium thiosulfate
Nationell ämneskategori
Medicinska och farmaceutiska grundvetenskaper Analytisk kemi Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-328151 (URN)10.1080/00016489.2017.1325006 (DOI)000407072000002 ()28537102 (PubMedID)
Forskningsfinansiär
AFA Försäkring
Tillgänglig från: 2017-08-18 Skapad: 2017-08-18 Senast uppdaterad: 2018-09-07Bibliografiskt granskad
Häggblad Sahlberg, S., Mortensen, A. C., Haglöf, J., Engskog, M. K. R., Arvidsson, T., Pettersson, C., . . . Nestor, M. (2017). Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells. International Journal of Oncology, 50(1), 5-14
Öppna denna publikation i ny flik eller fönster >>Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells
Visa övriga...
2017 (Engelska)Ingår i: International Journal of Oncology, ISSN 1019-6439, Vol. 50, nr 1, s. 5-14Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

AKT is a central protein in many cellular pathways such as cell survival, proliferation, glucose uptake, metabolism, angiogenesis, as well as radiation and drug response. The three isoforms of AKT (AKT1, AKT2 and AKT3) are proposed to have different physiological functions, properties and expression patterns in a cell type-dependent manner. As of yet, not much is known about the influence of the different AKT isoforms in the genome and their effects in the metabolism of colorectal cancer cells. In the present study, DLD-1 isogenic AKT1, AKT2 and AKT'/2 knockout colon cancer cell lines were used as a model system in conjunction with the parental cell line in order to further elucidate the differences between the AKT isoforms and how they are involved in various cellular pathways. This was done using genome wide expression analyses, metabolic profiling and cell migration assays. In conclusion, downregulation of genes in the cell adhesion, extracellular matrix and Notch-pathways and upregulation of apoptosis and metastasis inhibitory genes in the p53-pathway, confirm that the knockout of both AKT1 and AKT2 will attenuate metastasis and tumor cell growth. This was verified with a reduction in migration rate in the AKT1 KO and AKT2 KO and most explicitly in the AKT1/2 KO. Furthermore, the knockout of AKT1, AKT2 or both, resulted in a reduction in lactate and alanine, suggesting that the metabolism of carbohydrates and glutathione was impaired. This was further verified in gene expression analyses, showing downregulation of genes involved in glucose metabolism. Additionally, both AKT1 KO and AKT2 KO demonstrated an impaired fatty acid metabolism. However, genes were upregulated in the Wnt and cell proliferation pathways, which could oppose this effect. AKT inhibition should therefore be combined with other effectors to attain the best effect.

Nyckelord
Microarray, metabolism, cell migration AKT1, AKT2, AKT, PKB, gene expression, colon-cancer, DLD-1, metabolomics, CD44, CD133
Nationell ämneskategori
Biokemi och molekylärbiologi
Forskningsämne
Biomedicinsk strålningsvetenskap; Biologi med inriktning mot molekylär cellbiologi; Biologi med inriktning mot molekylärbiologi
Identifikatorer
urn:nbn:se:uu:diva-222834 (URN)10.3892/ijo.2016.3771 (DOI)000391419200001 ()
Tillgänglig från: 2014-04-14 Skapad: 2014-04-14 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
Niklison-Chirou, M. V., Erngren, I., Engskog, M. K., Haglöf, J., Picard, D., Remke, M., . . . Marino, S. (2017). TAp73 is a marker of glutamine addiction in medulloblastoma. Genes & Development, 31(17), 1738-1753
Öppna denna publikation i ny flik eller fönster >>TAp73 is a marker of glutamine addiction in medulloblastoma
Visa övriga...
2017 (Engelska)Ingår i: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 31, nr 17, s. 1738-1753Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma.

Ort, förlag, år, upplaga, sidor
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2017
Nyckelord
medulloblastoma, p73, glutamine, metabolomics
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-336829 (URN)10.1101/gad.302349.117 (DOI)000412275500004 ()28971956 (PubMedID)
Tillgänglig från: 2017-12-20 Skapad: 2017-12-20 Senast uppdaterad: 2017-12-20Bibliografiskt granskad
Elmsjö, A., Haglöf, J., Engskog, M. K. R., Nestor, M., Arvidsson, T. & Pettersson, C. (2017). The co-feature ratio, a novel method for the measurement of chromatographic and signal selectivity in LC-MS-based metabolomics.. Analytica Chimica Acta, 956, 40-47
Öppna denna publikation i ny flik eller fönster >>The co-feature ratio, a novel method for the measurement of chromatographic and signal selectivity in LC-MS-based metabolomics.
Visa övriga...
2017 (Engelska)Ingår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 956, s. 40-47Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Evaluation of analytical procedures, especially in regards to measuring chromatographic and signal selectivity, is highly challenging in untargeted metabolomics. The aim of this study was to suggest a new straightforward approach for a systematic examination of chromatographic and signal selectivity in LC-MS-based metabolomics. By calculating the ratio between each feature and its co-eluting features (the co-features), a measurement of the chromatographic selectivity (i.e. extent of co-elution) as well as the signal selectivity (e.g. amount of adduct formation) of each feature could be acquired, the co-feature ratio. This approach was used to examine possible differences in chromatographic and signal selectivity present in samples exposed to three different sample preparation procedures. The capability of the co-feature ratio was evaluated both in a classical targeted setting using isotope labelled standards as well as without standards in an untargeted setting. For the targeted analysis, several metabolites showed a skewed quantitative signal due to poor chromatographic selectivity and/or poor signal selectivity. Moreover, evaluation of the untargeted approach through multivariate analysis of the co-feature ratios demonstrated the possibility to screen for metabolites displaying poor chromatographic and/or signal selectivity characteristics. We conclude that the co-feature ratio can be a useful tool in the development and evaluation of analytical procedures in LC-MS-based metabolomics investigations. Increased selectivity through proper choice of analytical procedures may decrease the false positive and false negative discovery rate and thereby increase the validity of any metabolomic investigation.

Nationell ämneskategori
Analytisk kemi Farmaceutiska vetenskaper
Forskningsämne
Analytisk farmaceutisk kemi
Identifikatorer
urn:nbn:se:uu:diva-314239 (URN)10.1016/j.aca.2016.12.022 (DOI)000393252000005 ()28093124 (PubMedID)
Tillgänglig från: 2017-01-31 Skapad: 2017-01-31 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
Svan, A., Hedeland, M., Arvidsson, T. & Pettersson, C. (2017). The differences in matrix effects between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS analyzing blood plasma. In: : . Paper presented at HPLC 2017.
Öppna denna publikation i ny flik eller fönster >>The differences in matrix effects between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS analyzing blood plasma
2017 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
Abstract [en]

Introduction

The increasing popularity of supercritical fluid chromatography (SFC) in combination with electrospray ionization mass spectrometry (ESI/MS) within several fields calls for a deeper knowledge regarding this combination of techniques. The ESI source is known for its sensitivity regarding matrix effects, often a factor controlled during method development and validation using LC. The different chemistry and chromatographic selectivity of LC and SFC give potentially different impact on the ionization process in ESI; however, this an area still not well studied.   

Aim: To investigate how the matrix effects in ESI/MS differ for human plasma samples between SFC and reversed-phase LC, using generic screening conditions for both techniques, and a set of typical low molecular weight drug substances.

Methods

Pooled human plasma (500 µl) was precipitated using ice-cold acetonitrile (1000 µl). After mixing and centrifuging, 1200 µl of the supernatant were removed and evaporated at 40 ̊C. When dry, the samples were dissolved in 500µl water+0.1% FA (for LC) or acetonitrile:water 75:25 (for SFC). The samples were analyzed using SFC (Acquity UPC2, Waters®) and LC (Acquity UPLC, Waters®) and general screening conditions, using 10 min gradients. The same MS-system, a Q-ToF (Synapt G2-S, Waters®) acquiring in full scan mode, was used for detection with both separation techniques. The matrix effect was mainly evaluated using the Matrix Effect Profile, achieved from post-column compound infusions and injections of pretreated sample matrix and neat standards. From these data the average ME% was calculated for each data-point in the chromatogram, and through the full-scan mode using ToF, the compounds co-eluting with areas of suppression could be tentatively identified, suspected of creating the suppression. 

 

Results and discussion The Matrix Effect Profile-evaluation of the experiments, combining qualitative and quantitative information with the added ability to use HRMS-data to identify interfering compounds from the same experiments were most useful for our aim. Phospholipids, creatinine, polyethylene glycol and cluster formations are examples of important interferences co-eluting with areas of ion suppression, but with different impact depending on chromatographic technique. The results also showed several areas of enhancement using LC, an effect not seen using SFC. 

Nationell ämneskategori
Analytisk kemi
Forskningsämne
Analytisk farmaceutisk kemi
Identifikatorer
urn:nbn:se:uu:diva-341331 (URN)
Konferens
HPLC 2017
Tillgänglig från: 2018-02-07 Skapad: 2018-02-07 Senast uppdaterad: 2018-02-07
Engskog, M. K. R., Ersson, L., Haglöf, J., Arvidsson, T., Pettersson, C. & Brittebo, E. (2017). β-N-Methylamino-L-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling. Amino Acids, 49(5), 905-919
Öppna denna publikation i ny flik eller fönster >>β-N-Methylamino-L-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling
Visa övriga...
2017 (Engelska)Ingår i: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 49, nr 5, s. 905-919Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

β-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC-MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

Nyckelord
BMAA, Global metabolite profiling, MS, Metabolism, NMR, Neurotoxin
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-322142 (URN)10.1007/s00726-017-2391-8 (DOI)000399176200006 ()28161796 (PubMedID)
Forskningsfinansiär
Forskningsrådet Formas
Tillgänglig från: 2017-05-16 Skapad: 2017-05-16 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
Organisationer

Sök vidare i DiVA

Visa alla publikationer