Translocation and de novo synthesis of eicosapentaenoic acid (EPA) during nitrogen starvation in Nannochloropsis gaditana

The microalga Nannochloropsis gaditana is known for accumulating fatty acids, including the commercially interesting eicosapentaenoic acid (EPA) within the polar lipids (PL) and neutral lipids (NL). During microalgal growth EPA is mainly present in the PL. Upon nitrogen starvation N. gaditana accumulates large amounts of TAG in lipid bodies. The neutral lipid fraction will mainly consist of triacylglycerol (TAG). When expressed per total cell dry weight, the NL-localized EPA increased while the PL-localized EPA decreased, suggesting that EPA is translocated from the PL into the NL lipids during nitrogen starvation. Here, we elucidated the origin of EPA in NL of N. gaditana by firstly growing this microalga under optimal growth conditions with 13CO2 as the sole carbon source followed by nitrogen starvation with 12CO2 as the sole carbon source. By measuring both 12C and 13C fatty acid isotope species in time, the de novo synthesized fatty acids and the already present fatty acids can be distinguished. For the first time, we proved that actual translocation of EPA from the PL into the NL occurs during nitrogen starvation of N. gaditana. Next to being translocated, EPA was synthesized de novo in both PL and NL during nitrogen starvation. EPA was made by carbon reshuffling within the cell as well. EPA was the main fatty acid translocated, suggesting that the enzyme responsible for fatty acid translocation has a high specificity for EPA

Activation of Antioxidant Response Element in Mouse Primary Cortical Cultures with Sesquiterpene Lactones Isolated from Tanacetum parthenium

Tanacetum parthenium produces biologically active sesquiterpene lactones (SL). Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate a series of genes termed the antioxidant response element (ARE). Activation of Nrf2/ARE may be useful for the treatment of neurodegenerative disease. In this study we isolated 11 SL from T. parthenium with centrifugal partition chromatography and semipreparative HPLC. Compounds were screened in vitro for their ability to activate the ARE on primary mouse cortical cultures as well as for their toxicity towards the cultures. All SL containing the alpha-methylene-gamma-lactone moiety were able to activate the ARE and cause cellular toxicity. The structure-activity relationship among the SL isolated indicates that the guaianolides were more active and when lacking the endoperoxide functionality less toxic then the germacranolides.European Union [227448]; National Institute of Environmental Health Sciences [R01ES08089, R01ES10042

Activation of Antioxidant Response Element in Mouse Primary Cortical Cultures with Sesquiterpene Lactones Isolated from Tanacetum parthenium

Tanacetum parthenium produces biologically active sesquiterpene lactones (SL). Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate a series of genes termed the antioxidant response element (ARE). Activation of Nrf2/ARE may be useful for the treatment of neurodegenerative disease. In this study we isolated 11 SL from T. parthenium with centrifugal partition chromatography and semipreparative HPLC. Compounds were screened in vitro for their ability to activate the ARE on primary mouse cortical cultures as well as for their toxicity towards the cultures. All SL containing the alpha-methylene-gamma-lactone moiety were able to activate the ARE and cause cellular toxicity. The structure-activity relationship among the SL isolated indicates that the guaianolides were more active and when lacking the endoperoxide functionality less toxic then the germacranolides.European Union [227448]; National Institute of Environmental Health Sciences [R01ES08089, R01ES10042

EpiRILsand parentsQTL-mapping_rawLCMScdfs

EpiRILs and parents QTL-mapping raw LCMS dat

Cytotoxic activity of sesquiterpene lactones from Inula britannica on human cancer cell lines

Five new sesquiterpene lactones (1-5) were isolated from Inula britannica collected in the wild from Serbia along with five known compounds (6-10). Sesquiterpene lactones were isolated using centrifugal partition chromatography followed by combination of flash chromatography and semi-preparative HPLC. Isolated compounds were screened for cytotoxic activity on four different human cancer cell lines and their multi-drug resistant counterparts, as well as on normal human keratinocytes. Sesquiterpene lactones showed similar cytotoxic activity toward drug sensitive and drug resistant cancer cell lines. (C) 2013 Phytochemical Society of Europe. Published by Elsevier B. V. All rights reserved.European Union [227448]; Center for Biosystems Genomics part of the Netherlands Genomics Initiative; Netherlands Metabolomics Center part of the Netherlands Genomics Initiativ

Cytotoxic activity of sesquiterpene lactones from Inula britannica on human cancer cell lines

Five new sesquiterpene lactones (1-5) were isolated from Inula britannica collected in the wild from Serbia along with five known compounds (6-10). Sesquiterpene lactones were isolated using centrifugal partition chromatography followed by combination of flash chromatography and semi-preparative HPLC. Isolated compounds were screened for cytotoxic activity on four different human cancer cell lines and their multi-drug resistant counterparts, as well as on normal human keratinocytes. Sesquiterpene lactones showed similar cytotoxic activity toward drug sensitive and drug resistant cancer cell lines. (C) 2013 Phytochemical Society of Europe. Published by Elsevier B. V. All rights reserved.European Union [227448]; Center for Biosystems Genomics part of the Netherlands Genomics Initiative; Netherlands Metabolomics Center part of the Netherlands Genomics Initiativ