[U-13C]glucose tracing in activated WT, GOT1 or GLUD1 knockout CD8+ T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
TISSUE(S): Cultured Cells
PROVIDER: ST002364 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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| mwtab | Other |
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| ST002365 | MetabolomicsWorkbench
Project description:Breast cancer is one of the leading causes of cancer death. Recent studies found that arylamine N-acetyltransferase 1 (NAT1) is frequently upregulated in breast cancer, further suggesting NAT1 could be a potential therapeutic target for breast cancer. Previous publications have established that NAT1 knockout (KO) in breast cancer cell lines leads to growth reduction both in vitro and in vivo and metabolic changes. These reports suggest that NAT1 contributes to the energy metabolism of breast cancer cells. Proteomic analysis and non-targeted metabolomics suggested that NAT1 KO may change the fate of glucose as it relates to the TCA/KREB cycle of the mitochondria of breast cancer cells. In this current study, we used [U-13C]-glucose stable isotope resolved metabolomics to determine the effect of NAT1 KO on the metabolic profile of MDA-MB-231 breast cancer cells. We incubated breast cancer cells (MDA-MB-231 cells) and NAT1 Crispr KO cells (KO#2 and KO#5) with [U-13C]-glucose for 24 h. Tracer incubation polar metabolites from the cells were extracted and analyzed by 2DLC-MS, and metabolite differences were compared between the parental and NAT1 KO cells. Differences consistent between the two KO cells were considered changes due to the loss of NAT1. The data revealed decreases in the 13C enrichment of TCA/Krebs cycle intermediates in NAT1 KO cells compared to the MDA-MB-231 cells. Specifically, 13C-labeled citrate, isocitrate, a-ketoglutarate, fumarate, and malate were all decreased in NAT1 KO cells. We also detected increased 13C-labeled L-lactate levels in the NAT1 KO cells and decreased 13C enrichment in some nucleotides. Pathway analysis showed that arginine biosynthesis, alanine, aspartate and glutamate metabolism, and the TCA cycle were most affected. These data provide additional evidence supporting the impacts of NAT1 knockout on cellular energy metabolism. The data suggest that NAT1 expression is important for the proper functioning of mitochondria and the flux of glucose through the TCA/Krebs cycle in breast cancer cells. The metabolism changes in the fate of glucose in NAT1 KO breast cancer cells offer more insight into the role of NAT1 in energy metabolism and the growth of breast cancer cells. These data provide additional evidence that NAT1 may be a useful therapeutic target for breast cancer.
| S-EPMC10137864 | biostudies-literature
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| ST002363 | MetabolomicsWorkbench
Project description:The objective of this study was to determine if a subset of regulatory T cells (Tregs) expressing the transcription factor, Zbtb20, played a unique role in the function of the immune system. Genetic reporter mice were used to isolate Zbtb20-expressing Tregs as well as activated (CD62Llo) and naive (CD62Lhi) Tregs. The gene expression in these cells was determined with RNA-seq.
2022-02-25 | E-MTAB-11442 | biostudies-arrayexpress
Project description:Samples-WT Basal condition primary cortex cells; WT B27 Starved-Primary cortex cells starved overnight without B27 supplement media. WT AA Starved-Primary cortex cell starved without amino acid for 2 hours. WT AA Refed-Primary cortex cell refed for 1 hour after amino acid starvation. KO Basal-SLC38 Knockout Primary cortex cells starved overnight without B27 supplement media. KO B27 Starved-SLC38 Knockout Primary cortex cell starved without amino acid for 2 hours. KO AA starved-SLC38 Knockout Primary cortex cell refed for 1 hour after amino acid starvation. KO AA Refed-SLC38 Knockout Primary cortex cell refed for 1 hour after amino acid starvation.
2021-06-03 | E-MTAB-10413 | biostudies-arrayexpress
Project description:LC-MS and GC-MS raw data for 13C6-glucose tracing in PDA cells expressing sgROSA or sgRNA targeting methionine sulfoxide reductase A
2022-05-21 | MSV000089514 | MassIVE
Project description:ObjectiveAn increased risk of bleeding is observed in patients receiving activated protein C (APC), which may be a limiting factor for the application of novel APC therapies. Since APC's therapeutic effects often require its cytoprotective activities on cells but not APC's anticoagulant activities, an agent that specifically antagonizes APC's anticoagulant effects but not its cytoprotective effects could provide an effective means to control concerns for risk of bleeding. We hypothesized that superFVa, an engineered activated FVa-variant that restores hemostasis in hemophilia could reduce APC-induced bleeding.Approach and resultsSuperFVa was engineered with mutations of the APC cleavage sites (Arg506/306/679Gln) and a disulfide bond (Cys609-Cys1691) between the A2 and A3 domains, which augment its biological activity and cause high resistance to APC. SuperFVa normalized APC-prolonged clotting times and restored APC-suppressed thrombin generation in human and murine plasma at concentrations where wild-type (wt) FVa did not show effects. Following intravenous injection of APC into BALB/c mice, addition to whole blood ex vivo of superFVa but not wt-FVa significantly normalized whole blood clotting. Blood loss following tail clip or liver laceration was significantly reduced when superFVa was administered intravenously to BALB/c mice prior to intravenous APC-treatment. Furthermore, superFVa abolished mortality (∼50%) associated with excessive bleeding following liver laceration in mice treated with APC.ConclusionsOur results provide proof of concept that superFVa is effective in preventing APC-induced bleeding and may provide therapeutic benefits as a prohemostatic agent in various situations where bleeding is a serious risk.
| S-EPMC4134195 | biostudies-literature
Project description:Knockout (KO) mice missing the sweet taste receptor subunit T1R3 or the signaling protein TRPM5 have greatly attenuated sweetener preferences. Yet both types of KO mice develop preferences for glucose but not fructose in 24-h tests, which has been attributed to the postoral reinforcing actions of glucose. Here we probed for residual sugar taste sensitivity in KO mice. Unlike wildtype (WT) mice, food-restricted T1R3 KO and TRPM5 KO mice displayed little attraction for 8% glucose and 8% fructose in 1-min, two-bottle choice tests. However, in 1-h tests about half of the T1R3 KO mice displayed a significant preference for glucose over fructose (78-84%), while WT mice showed either no or weak preferences (41-56%) for glucose. Following one-bottle training sessions, WT mice display greater glucose preferences although still weaker than those observed in T1R3 KO mice. In contrast, TRPM5 KO mice were indifferent to sugars in 1-h tests but developed a strong preference for glucose over fructose in 24-h tests. T1R3 taste cells contain the sodium glucose cotransporter 1 (SGLT1) and the ATP-gated K+ (KATP) metabolic sensor, which may mediate the unlearned glucose preference displayed by T1R3 KO mice. Unlike WT mice, many T1R3 KO mice strongly preferred glucose to a non-metabolizable glucose analog (α-methyl-D-glucopyranoside, MDG) in initial 1-h choice tests. Glucose and MDG are both ligands for SGLT1 which indicates that SGLT1 sensing does not mediate the glucose preference of T1R3 KO mice. Instead, KATP sensing and/or other oral sensors are implicated. The MDG findings also argue against postoral sensing as the primary source of the initial glucose preference displayed by T1R3 KO mice. Why only half of the T1R3 KO mice showed this preference in 1-h tests remains to be determined. All T1R3 KO mice preferred glucose to fructose in 24-h tests, which appears to be due to both oral and postoral glucose sensing.
| S-EPMC7417196 | biostudies-literature