Ether Lipid Metabolism, GPI Anchor Biosynthesis, and Signal Transduction are Putative Targets for Anti-Leishmanial Alkyl Phospholipid Analogues

1996 ◽  
pp. 201-211 ◽  
Author(s):  
H. Lux ◽  
D. T. Hart ◽  
P. J. Parker ◽  
T. Klenner
Keyword(s):  
Signal Transduction ◽  
Lipid Metabolism ◽  
Ether Lipid ◽  
Gpi Anchor

scholarly journals Triple-Knockout, Synuclein-Free Mice Display Compromised Lipid Pattern

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3078
Author(s):  
Irina A. Guschina ◽  
Natalia Ninkina ◽  
Andrei Roman ◽  
Mikhail V. Pokrovskiy ◽  
Vladimir L. Buchman
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Family Members ◽  
Ether Lipid ◽  
Brain Regions ◽  
Membrane Lipid ◽  
Lipid Binding ◽  
Synaptic Functions ◽  
Ethanolamine Plasmalogens ◽  
Lipid Pattern

Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson’s disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.

scholarly journals Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification

2008 ◽  
Vol 228 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Daniel K. Nomura ◽  
Kazutoshi Fujioka ◽  
Roger S. Issa ◽  
Anna M. Ward ◽  
Benjamin F. Cravatt ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Ether Lipid ◽  
Serine Hydrolase ◽  
Dual Roles ◽  
Organophosphate Detoxification

scholarly journals Transcriptome Response to Drought, Rehydration and Re-Dehydration in Potato

2019 ◽  
Vol 21 (1) ◽  
pp. 159 ◽  
Author(s):  
Yongkun Chen ◽  
Canhui Li ◽  
Jing Yi ◽  
Yu Yang ◽  
Chunxia Lei ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Gene Regulation ◽  
Lipid Metabolism ◽  
Drought Stress ◽  
Sugar Metabolism ◽  
Rna Seq ◽  
Drought Tolerant ◽  
Cell Components ◽  
Drought Hardening

Potato is an important food crop and its production is susceptible to drought. Drought stress in crop growth is usually multiple- or long-term. In this study, the drought tolerant potato landrace Jancko Sisu Yari was treated with drought stress, rehydration and re-dehydration, and RNA-seq was applied to analyze the characteristics of gene regulation during these treatments. The results showed that drought-responsive genes mainly involved photosynthesis, signal transduction, lipid metabolism, sugar metabolism, wax synthesis, cell wall regulation, osmotic adjustment. Potato also can be recovered well in the re-emergence of water through gene regulation. The recovery of rehydration mainly related to patatin, lipid metabolism, sugar metabolism, flavonoids metabolism and detoxification besides the reverse expression of the most of drought-responsive genes. The previous drought stress can produce a positive responsive ability to the subsequent drought by drought hardening. Drought hardening was not only reflected in the drought-responsive genes related to the modified structure and cell components, but also in the hardening of gene expression or the “memory” of drought-responsive genes. Abundant genes involved photosynthesis, signal transduction, sugar metabolism, protease and protease inhibitors, flavonoids metabolism, transporters and transcription factors were subject to drought hardening or memorized drought in potato.

scholarly journals Tetrahydrobiopterin and alkylglycerol monooxygenase substantially alter the murine macrophage lipidome

2015 ◽  
Vol 112 (8) ◽  
pp. 2431-2436 ◽  
Author(s):  
Katrin Watschinger ◽  
Markus A. Keller ◽  
Eileen McNeill ◽  
Mohammad T. Alam ◽  
Steven Lai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Metabolism ◽  
Transforming Growth Factor ◽  
Ether Lipid ◽  
Mouse Bone Marrow ◽  
Monooxygenase Activity ◽  
Lipid Species ◽  
Primary Mouse ◽  
Ifn Γ

Tetrahydrobiopterin is a cofactor synthesized from GTP with well-known roles in enzymatic nitric oxide synthesis and aromatic amino acid hydroxylation. It is used to treat mild forms of phenylketonuria. Less is known about the role of tetrahydrobiopterin in lipid metabolism, although it is essential for irreversible ether lipid cleavage by alkylglycerol monooxygenase. Here we found intracellular alkylglycerol monooxygenase activity to be an important regulator of alkylglycerol metabolism in intact murine RAW264.7 macrophage-like cells. Alkylglycerol monooxygenase was expressed and active also in primary mouse bone marrow-derived monocytes and “alternatively activated” M2 macrophages obtained by interleukin 4 treatment, but almost missing in M1 macrophages obtained by IFN-γ and lipopolysaccharide treatment. The cellular lipidome of RAW264.7 was markedly changed in a parallel way by modulation of alkylglycerol monooxygenase expression and of tetrahydrobiopterin biosynthesis affecting not only various ether lipid species upstream of alkylglycerol monooxygenase but also other more complex lipids including glycosylated ceramides and cardiolipins, which have no direct connection to ether lipid pathways. Alkylglycerol monooxygenase activity manipulation modulated the IFN-γ/lipopolysaccharide–induced expression of inducible nitric oxide synthase, interleukin-1β, and interleukin 1 receptor antagonist but not transforming growth factor β1, suggesting that alkylglycerol monooxygenase activity affects IFN-γ/lipopolysaccharide signaling. Our results demonstrate a central role of tetrahydrobiopterin and alkylglycerol monooxygenase in ether lipid metabolism of murine macrophages and reveal that alteration of alkylglycerol monooxygenase activity has a profound impact on the lipidome also beyond the class of ether lipids.

scholarly journals Intracellular cleavage of glycosylphosphatidylinositol by phospholipase D induces activation of protein kinase Cα

1999 ◽  
Vol 342 (2) ◽  
pp. 449-455 ◽  
Author(s):  
Hiroshi TSUJIOKA ◽  
Noboru TAKAMI ◽  
Yoshio MISUMI ◽  
Yukio IKEHARA
Keyword(s):  
Signal Transduction ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Phospholipase D ◽  
Secretory Pathway ◽  
Gradient Centrifugation ◽  
Endoplasmic Reticulum Membrane ◽  
Gpi Anchor ◽  
Protein Kinase Cα ◽  
In Cells

Many proteins are anchored to the cell membrane by glycosylphosphatidylinositol (GPI). One of the functions proposed for the GPI anchor is as a possible mediator in signal transduction through its hydrolysis. GPI-specific phospholipase D (GPI-PLD) is a secretory protein that is suggested to be involved in the release of GPI-anchored protein from the membrane. In the present study we examined how GPI-PLD is involved in signal transduction. When introduced exogenously and overexpressed in cells, GPI-PLD cleaved the GPI anchors in the early secretory pathway, possibly in the endoplasmic reticulum, resulting in an increased production of diacylglycerol. Experiments in vitro and in vivo showed that the association of protein kinase Cα (PKCα) with membranes was increased markedly by expression of GPI-PLD in cells. Furthermore, sucrose-density-gradient centrifugation and immunofluorescence microscopy demonstrated that PKCα was translocated to the endoplasmic reticulum membrane in cells expressing GPI-PLD, in contrast with its association with the plasma membrane in cells treated with PMA. We also confirmed that the phosphorylation of c-Fos as well as PKCα itself was greatly enhanced by the expression of GPI-PLD. Taken together, these results suggest that GPI-PLD is involved in intracellular cleavage of the GPI anchor, which is a new potential source of diacylglycerol production to activate PKCα.

Signal transduction in EJ-H-ras -transformed cells: De novo synthesis of diacylglycerol and subversion of agonist-stimulated inositol lipid metabolism

FEBS Letters ◽  
1989 ◽  
Vol 252 (1-2) ◽  
pp. 129-134 ◽  
Author(s):  
Vincenzo P. Chiarugi ◽  
Lucia Magnelli ◽  
Franca Pasquali ◽  
Gabriele Basi ◽  
Marco Ruggiero
Keyword(s):  
Signal Transduction ◽  
Lipid Metabolism ◽  
De Novo ◽  
Transformed Cells ◽  
De Novo Synthesis

scholarly journals Triple-knockout, synuclein-free mice display compromised lipid pattern

2020 ◽  
Author(s):  
Irina Guschina ◽  
Natalia Ninkina ◽  
Andrei Y. Roman ◽  
Mikhail V. Pokrovskiy ◽  
Vladimir L. Buchman
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Lipid Membranes ◽  
Ether Lipid ◽  
Fatty Acid Analysis ◽  
Membrane Lipid ◽  
Lipid Binding ◽  
Synaptic Functions ◽  
Ethanolamine Plasmalogens ◽  
Lipid Pattern

Abstract Background: Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. All members of the synuclein family interact robustly with lipid membranes, and appear to be important for the physiological functions of proteins while influencing the pathological aggregation of α-synuclein. Methods: The following tissues were used for lipid and fatty acid analysis: plasma, liver and two brain areas (cortex and midbrain). Lipid classes were separated using thin-layer chromatography. Fatty acids were analysed using gas chromatography. Results: We describe the importance of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and circulated plasma non-esterified fatty acids in synuclein free mice. In midbrain, observed changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER) were counterbalanced. In midbrain, we recorded a notable reduction in ethanolamine plasmalogens in synuclein free mice and consider this an important finding considering the abnormal ether lipid metabolism usually associated with neurological disorders.Conclusions: In summary, our data demonstrate that synuclein deficiency can result in alterations of PUFA synthesis, storage lipid accumulation in liver, and reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members resulted in more pronounced lipid modifications then previously showed by us γ-synuclein deficiency. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.

scholarly journals Increased expression of HIST1H1D in esophageal carcinoma predicts poor survival: A study base on TCGA database

2021 ◽  
Author(s):  
Shan Huang ◽  
Hanwen Huang ◽  
Mingchu Liao ◽  
Caiqun Tian ◽  
Rong Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lipid Metabolism ◽  
Esophageal Carcinoma ◽  
Acid Metabolism ◽  
Ether Lipid ◽  
Smooth Muscle Contraction ◽  
Poor Survival ◽  
Acid Biosynthesis ◽  
Phenylalanine Metabolism ◽  
Vascular Smooth Muscle Contraction

Abstract Background: Expression level of HIST1H1D, a linker histone H1 gene, was reported to be associated with poor prognosis in some malignant tumors. Online database showed that HIST1H1D was increased in esophageal carcinoma. The current study aimed to evaluated the role of HIST1H1D in esophageal carcinoma using online data from The Cancer Genome Atlas (TCGA).Methods. Wilcoxon signed-rank test, cox regression analysis and multivariant analysis were used to analyze the relationship between clinical characteristic and HIST1H1D expression level. Kaplan-Meier method was used to analyze the association of HIST1H1D and overall survival. Gene set enrichment analysis (GSEA) was used to identify HIST1H1D-related signaling pathway.Results. Compared to normal sample, HIST1H1D was significantly increased in esophageal carcinoma sample (p=0.000). High HIST1H1D expression was associated with poor survival (p=0.035). Univariate analysis showed that high HIST1H1D expression was associated with a poor overall survival (HR:1.19, 95% confidence interval [CI]: 1.05-1.34, p=0.01). Multivariate analysis indicated that HIST1H1D remained an independent prognostic predictor of overall survival (HR:1.18, 95% confidence interval [CI]: 1.02-1.36, p=0.03). GSEA revealed that alpha linolenic acid metabolism, arachidonic acid metabolism, histidine metabolism, vascular smooth muscle contraction, primary bile acid biosynthesis, phenylalanine metabolism and ether lipid metabolism were enriched in HIST1H1D high expression phenotype.Conclusions: HIST1H1D may sever as a potential prognostic predictor of poor survival in esophageal carcinoma. Lipid metabolism, histidine metabolism, vascular smooth muscle contraction, primary bile acid biosynthesis, phenylalanine metabolism and ether lipid metabolism may be the key signaling pathway regulated by HIST1H1D.

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