Primary Metabolism and Medium-Chain Fatty Acid Alterations Precede Long-Chain Fatty Acid Changes Impacting Neutral Lipid Metabolism in Response to an Anticancer Lysophosphatidylcholine Analogue in Yeast
| العنوان: | Primary Metabolism and Medium-Chain Fatty Acid Alterations Precede Long-Chain Fatty Acid Changes Impacting Neutral Lipid Metabolism in Response to an Anticancer Lysophosphatidylcholine Analogue in Yeast |
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| المؤلفون: | Saikumari Y. Krishnaiah, Raymond J. Turner, Aalim M. Weljie, Vanina Zaremberg, Nicolas P. Tambellini |
| المصدر: | Journal of Proteome Research. 16:3741-3752 |
| بيانات النشر: | American Chemical Society (ACS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Citric Acid Cycle, Saccharomyces cerevisiae, Fatty Acids, Nonesterified, Biology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Lipidomics, Metabolomics, Medium chain fatty acid, chemistry.chemical_classification, Fatty acid metabolism, Fatty Acids, Lysophosphatidylcholines, Phospholipid Ethers, Fatty acid, Lipid metabolism, General Chemistry, Lipid Metabolism, Dietary Fats, Oxidative Stress, 030104 developmental biology, Lysophosphatidylcholine, chemistry, Long chain fatty acid, Edelfosine |
| الوصف: | The nonmetabolizable lysophosphatidylcholine (LysoPC) analogue edelfosine is the prototype of a class of compounds being investigated for their potential as selective chemotherapeutic agents. Edelfosine targets membranes, disturbing cellular homeostasis. Is not clear at this point how membrane alterations are communicated between intracellular compartments leading to growth inhibition and eventual cell death. In the present study, a combined metabolomics/lipidomics approach for the unbiased identification of metabolic pathways altered in yeast treated with sublethal concentrations of the LysoPC analogue was employed. Mass spectrometry of polar metabolites, fatty acids, and lipidomic profiling was used to study the effects of edelfosine on yeast metabolism. Amino acid and sugar metabolism, the Krebs cycle, and fatty acid profiles were most disrupted, with polar metabolites and short-medium chain fatty acid changes preceding long and very long-chain fatty acid variations. Initial increases in metabolites such as trehalose, proline, and γ-amino butyric acid with a concomitant decrease in metabolites of the Krebs cycle, citrate and fumarate, are interpreted as a cellular attempt to offset oxidative stress in response to mitochondrial dysfunction induced by the treatment. Notably, alanine, inositol, and myristoleic acid showed a steady increase during the period analyzed (2, 4, and 6 h after treatment). Of importance was the finding that edelfosine induced significant alterations in neutral glycerolipid metabolism resulting in a significant increase in the signaling lipid diacylglycerol. |
| تدمد: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.7b00430 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::851629efe342172b3c18cc68c11980f4 https://doi.org/10.1021/acs.jproteome.7b00430 |
| رقم الانضمام: | edsair.doi.dedup.....851629efe342172b3c18cc68c11980f4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15353907 15353893 |
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| DOI: | 10.1021/acs.jproteome.7b00430 |