Transcriptomics of pig vascular endothelial cells by D-malate treatment
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE239494 | GEO | 2023/08/02
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: Understanding the mechanism of malate accumulation in plants is beneficial for both plant nutrient and human health. However, little is known regarding regulation of malate accumulation in horticulture plants such as tomato. The goals of this study are to investigate potential regulation network of Al-Activated Malate Transporter 9 (ALMT9) which is the major locus responsible for the variation in fruit malate concentration observed in cultivared tomato. Methods: The transcriptomes of fruit at ripening stage from CK and SlALMT9 overexpressing line1 were evaluated using single-ended sequencing of Illumina HiSeq 2500. Raw sequences were filtered and the resulting sets of clean reads were used for the following analysis by tophat and edgeR software. Results: Among 1,887 differentially expressed genes, some structural genes involved in sugar and organic acid metabolism were differently expressed in SlALMT9 overexpressing line, which partially coincide with changes of sugar and organic acid concentration. PR genes was also altered in the OX lines, in agreement with previous study that tomato fruit malate is involved in pathogen infection. Three members of malate transporters, MATE (multidrug and toxin efflux), were up-regulated (SlMATE5 and 6) or down-regulated (SlMATE9) . Besides, three sugar transport proteins and four vacuole membrane or plasma membrane proteins were up-regulated in OX line Conclusions: Using RNA-seq analysis, 1,887 differentially expressed genes was revealed. Among them, several genes related to sugar and organic acid metabolism and transport, pathogen resistances were identified. This transcriptome study provides insight into the regulatory mechanism of fruit malate accumulation and the effect of the SlALMT9 to primary metabolism.
2018-02-16 | GSE89772 | GEO
Project description:Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl levels. These elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.
2024-10-24 | GSE273694 | GEO
Project description:To better understand the malate-mediated metabolism and related regulatory profiles of L. hongkongensis, we compared the respective expression profiles of L. hongkongensis cells grown in modified M63 media supplemented with or without malate using high-throughput RNA-sequencing.
2019-09-30 | GSE135058 | GEO
Project description:Transcriptomics of pig vascular endothelial cells by D-malate treatment
| PRJNA999452 | ENA
Project description:Ne-lysine acetylation within the lumen of the endoplasmic reticulum (ER) is a recently characterized protein quality control system that positively selects properly folded glycoproteins in the early secretory pathway. Overexpression of the ER acetyl-CoA transporter AT-1 in mouse forebrain neurons results in increased dendritic branching, spine formation, and an autistic-like phenotype that is attributed to altered glycoprotein flux through the secretory pathway. AT-1 overexpressing neurons maintain the cytosolic pool of acetyl-CoA by upregulation of SLC25A1, the mitochondrial citrate/malate antiporter, and ATP citrate lyase (ACLY), which converts cytosolic citrate into acetyl-CoA. All three genes have been associated with autism spectrum disorder (ASD), suggesting that aberrant cytosolic to ER flux of acetyl-CoA can be a mechanistic driver for the development of ASD. We therefore generated a SLC25A1 neuron transgenic (nTg) mouse, which displayed autistic-like behaviors with a jumping stereotypy. The mice exhibited increased steady-state levels of citrate and acetyl-CoA, disrupted white matter integrity with activated microglia, and altered synaptic plasticity and morphology. Finally, acetylomic and proteomic analysis revealed differential adaptations in the hippocampus and cortex. Overall, our study reinforces the connection between aberrant cytosol-to-ER flux of acetyl-CoA flux and the development of an autistic-like phenotype.
2022-02-26 | PXD025415 | Pride
Project description:Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote efficient energy metabolism. We herein discover pantothenate kinase 4 (PanK4) as a conserved exercise target with high abundance in muscle. Germline deletion of Pank4 reduces circulating IGF-1 and stunts growth in mice. Muscle-specific deletion of Pank4 leads to a reduction in carnitzed and in impaired fatty acid oxidation in oxidative muscle which is related to higher acetyl-CoA and malonyl levels. Acetyl-CoA levels were persistently elevated in SkM lacking PanK4, independent of prandial state. In addition to perturbations of fatty acid oxidation, high SkM acetyl-CoA levels were associated with whole-body glucose intolerance, impaired insulin-stimulated glucose uptake into glycolytic SkM and impaired SkM glucose uptake during exercise. Conversely, we show that an increase in PanK4 lowers acetyl-CoA and increases glucose uptake in glycolytic SkM. Our findings identify PanK4 as a conserved exercise target that regulates SkM acetyl-CoA levels and plays a key role in lipid and glucose metabolism.
2024-10-25 | PXD057017 | Pride
Project description:The malate shuttle is traditionally known to maintain the NAD+/NADH balance between the cytosol and mitochondria. Whether the malate shuttle has additional functions was unknown. Here we show that chronic viral infections induced the expression of GOT1, the key enzyme in the malate shuttle, in CD8+ T cells. Got1 deficiency indeed decreased the NAD+/NADH ratio and dampened antiviral CD8+ T cell responses to chronic infection; however, increasing the NAD+/NADH ratio did not restore antiviral T cell responses. Got1 deficiency reduced the production of the ammonia scavenger 2-ketoglutarate and led to toxic ammonia accumulation in CD8+ T cells. Supplementation with 2-ketoglutarate assimilated and detoxified ammonia in Got1-deficient T cells and restored antiviral responses. This study suggests that the major function of the malate shuttle in CD8+ T cells is not to maintain the NAD+/NADH ratio, but rather to detoxify ammonia and enable sustainable ammonia-neutral glutamine catabolism in CD8+ T cells during chronic infections.
2023-09-01 | GSE220876 | GEO
Project description:Mitochondrial Malate Dehydrogenase 2 has been identified as an RNA-binding protein in several RNA-interactome capture studies. Here, we used eCLIP to identify the RNA targets bound by human MDH2. We identify cytosolic RNA targets for MDH2, as well as several mitochondrial tRNAs.
2024-06-26 | GSE249145 | GEO
Project description:Endoplasmic-reticulum (ER)-based N-lysine acetylation is a positive selection marker for properly folded glycoproteins in the early secretory pathway, serving as an important protein quality control system. Excessive N-lysine acetylation within the ER via overexpression of the acetyl-CoA transporter AT-1 results in altered glycoprotein flux through the secretory pathway, which dramatically impacts dendritic branching and spine formation causing an autistic-like phenotype in the mouse. AT-1 works in concert with SLC25A1, the citrate/malate antiporter in the mitochondria, SLC13A5, the plasma membrane sodium/citrate synporter, and ATP citrate lyase (ACLY), the cytosolic enzyme that converts citrate into acetyl-CoA, in order to maintain the cytosolic-to-ER flux of acetyl-CoA. As such, we generated the SLC13A5 neuron transgenic (nTg) mouse with the hypothesis that increasing cytosolic citrate would impact acetyl-CoA flux into the ER and recapitulate the autistic-like AT-1 nTg model. Here, we demonstrated the SLC13A5 nTg mouse exhibits autistic-like behaviors with a jumping stereotypy. The mice displayed disrupted white matter integrity and altered synaptic structure and function. Finally, analysis of both the proteome and acetylome revealed unique adaptations in the hippocampus and cortex to SLC13A5 overexpression, implicating the importance of metabolic consequences of altered cytosolic citrate/acetyl-CoA availability in the neuron. Overall, our results corroborate the mechanistic link between aberrant intracellular citrate/acetyl-CoA flux and the development of an autistic-like phenotype.
2021-08-26 | PXD026624 | Pride
Project description:Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. The experiments were performed in quadruplicates for each condition with a total of 12 samples
2014-08-05 | E-GEOD-57488 | biostudies-arrayexpress