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BMC Microbiology May 2024The outer membrane (OM) of Gram-negative bacteria acts as an effective barrier to protect against toxic compounds. By nature, the OM is asymmetric with the highly packed... (Review)
Review
The outer membrane (OM) of Gram-negative bacteria acts as an effective barrier to protect against toxic compounds. By nature, the OM is asymmetric with the highly packed lipopolysaccharide (LPS) at the outer leaflet and glycerophospholipids at the inner leaflet. OM asymmetry is maintained by the Mla system, in which is responsible for the retrograde transport of glycerophospholipids from the OM to the inner membrane. This system is comprised of six Mla proteins, including MlaA, an OM lipoprotein involved in the removal of glycerophospholipids that are mis-localized at the outer leaflet of the OM. Interestingly, MlaA was initially identified - and called VacJ - based on its role in the intracellular spreading of Shigella flexneri.Many open questions remain with respect to the Mla system and the mechanism involved in the translocation of mislocated glycerophospholipids at the outer leaflet of the OM, by MlaA. After summarizing the current knowledge on MlaA, we focus on the impact of mlaA deletion on OM lipid composition and biophysical properties of the OM. How changes in OM lipid composition and biophysical properties can impact the generation of membrane vesicles and membrane permeability is discussed. Finally, we explore whether and how MlaA might be a candidate for improving the activity of antibiotics and as a vaccine candidate.Efforts dedicated to understanding the relationship between the OM lipid composition and the mechanical strength of the bacterial envelope and, in turn, how such properties act against external stress, are needed for the design of new targets or drugs for Gram-negative infections.
Topics: Bacterial Outer Membrane; Bacterial Outer Membrane Proteins; Membrane Lipids; Gram-Negative Bacteria; Glycerophospholipids; Shigella flexneri
PubMed: 38802775
DOI: 10.1186/s12866-023-03138-8 -
Archives of Biochemistry and Biophysics Jul 2024Phosphatidylinositol 4,5-bisphosphate (PIP), as well as other anionic phospholipids, play a pivotal role in various cellular processes, including ion channel regulation,... (Review)
Review
Phosphatidylinositol 4,5-bisphosphate (PIP), as well as other anionic phospholipids, play a pivotal role in various cellular processes, including ion channel regulation, receptor trafficking, and intracellular signaling pathways. The binding of volatile anesthetics and propofol to PIP leads to alterations in PIP-mediated signaling causing modulation of ion channels such as ɣ-aminobutyric acid type A (GABA) receptors, voltage-gated calcium channels, and potassium channels through various mechanisms. Additionally, the interaction between anionic phospholipids and G protein-coupled receptors plays a critical role in various anesthetic pathways, with these anesthetic-induced changes impacting PIP levels which cause cascading effects on receptor trafficking, including GABA receptor internalization. This comprehensive review of various mechanisms of interaction provides insights into the intricate interplay between PIP signaling and anesthetic-induced changes, shedding light on the molecular mechanisms underlying anesthesia.
Topics: Propofol; Phosphatidylinositol 4,5-Diphosphate; Signal Transduction; Humans; Animals; Anesthetics, Inhalation; Receptors, GABA-A
PubMed: 38801966
DOI: 10.1016/j.abb.2024.110045 -
PeerJ 2024As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of...
As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Glycerophospholipids; Coumarins; Lipidomics; Mice; Chromatography, Liquid; Male; Disease Models, Animal; Mice, Inbred C57BL; Diet, High-Fat; Mass Spectrometry; Lipid Metabolism
PubMed: 38799063
DOI: 10.7717/peerj.17380 -
Journal of Oleo Science Jun 2024Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary...
Similar Distribution between EPA-containing Phosphatidylcholine and Mesenchymal Stem Marker Positive Cells in the Aortic Wall of Abdominal Aortic Aneurysm Model Rat Fed a Low-EPA Content Diet.
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary components are closely associated with AAA. Among those dietary components, eicosapentaenoic acid (EPA) is considered to have suppressive effects on AAA. In the AAA wall of AAA model animals bred under EPA-rich condition, the distribution of EPA-containing phosphatidylcholine (EPA-PC) has been reported to be similar to that of the markers of mesenchymal stem cells (MSCs) and M2 macrophages. These data suggest that the suppressive effects of EPA on AAA are related to preferential distribution of specific cells in the aortic wall. However, the distribution of EPA-PC in the AAA wall of AAA model animals fed a diet containing small amounts of EPA, which has not been reported to inhibit AAA, has not yet been explored. In the present study, we visualized the distribution of EPA-PCs in the AAA wall of AAA model animals fed a diet containing small amounts of EPA (1.5% EPA in the fatty acid composition) to elucidate the vasoprotective effects of EPA. Positive areas for markers of MSCs were significantly higher in the region where EPA-PC was abundant compared to the regions where EPA-PC was weakly detected, but not for markers of M2 macrophages, matrix metalloproteinase (MMP)-2, and MMP-9. The distribution of MSC markers was similar to that of EPA-PC but not that of M2 macrophages and MMPs. These data suggest preferential incorporation of EPA into MSCs under the conditions used in this study. The incorporation of EPA into certain cells may differ according to dietary conditions, which affect the development of AAA.
Topics: Animals; Eicosapentaenoic Acid; Aortic Aneurysm, Abdominal; Mesenchymal Stem Cells; Disease Models, Animal; Phosphatidylcholines; Aorta, Abdominal; Male; Diet; Rats; Macrophages; Biomarkers; Matrix Metalloproteinase 9
PubMed: 38797690
DOI: 10.5650/jos.ess23269 -
Current Opinion in Cell Biology Jun 2024Phosphoinositides broadly impact membrane dynamics, signal transduction and cellular physiology. The orchestration of signaling complexity by this seemingly simple... (Review)
Review
Phosphoinositides broadly impact membrane dynamics, signal transduction and cellular physiology. The orchestration of signaling complexity by this seemingly simple metabolic pathway remains an open question. It is increasingly evident that comprehending the complexity of the phosphoinositides metabolic network requires a systems view based on nonlinear dynamics, where the products of metabolism can either positively or negatively modulate enzymatic function. These feedback and feedforward loops may be paradoxical, leading to counterintuitive effects. In this review, we introduce the framework of nonlinear dynamics, emphasizing distinct dynamical regimes such as the excitable state, oscillations, and mixed-mode oscillations-all of which have been experimentally observed in phosphoinositide metabolisms. We delve into how these dynamical behaviors arise from one or multiple network motifs, including positive and negative feedback loops, coherent and incoherent feedforward loops. We explore the current understanding of the molecular circuits responsible for these behaviors. While mapping these circuits presents both conceptual and experimental challenges, redefining cellular behavior based on dynamical state, lipid fluxes, time delay, and network topology is likely essential for a comprehensive understanding of this fundamental metabolic network.
Topics: Phosphatidylinositols; Humans; Animals; Nonlinear Dynamics; Signal Transduction; Metabolic Networks and Pathways; Models, Biological
PubMed: 38797149
DOI: 10.1016/j.ceb.2024.102373 -
Lipids in Health and Disease May 2024Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction,... (Review)
Review
Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography-tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice.
Topics: Humans; Prognosis; Neoplasms; Lipidomics; Biomarkers, Tumor; Mass Spectrometry; Female; Lipids; Male; Breast Neoplasms; Prostatic Neoplasms; Lysophospholipids; Colorectal Neoplasms
PubMed: 38796445
DOI: 10.1186/s12944-024-02121-0 -
Biochimica Et Biophysica Acta.... Aug 2024Activating mutations in the CTNNB1 gene encoding β-catenin are among the most frequently observed oncogenic alterations in hepatocellular carcinoma (HCC). Profound...
Activating mutations in the CTNNB1 gene encoding β-catenin are among the most frequently observed oncogenic alterations in hepatocellular carcinoma (HCC). Profound alterations in lipid metabolism, including increases in fatty acid oxidation and transformation of the phospholipidome, occur in HCC with CTNNB1 mutations, but it is unclear what mechanisms give rise to these changes. We employed untargeted lipidomics and targeted isotope tracing to measure phospholipid synthesis activity in an inducible human liver cell line expressing mutant β-catenin, as well as in transgenic zebrafish with activated β-catenin-driven HCC. In both models, activated β-catenin expression was associated with large changes in the lipidome including conserved increases in acylcarnitines and ceramides and decreases in triglycerides. Lipid isotope tracing analysis in human cells revealed a reduction in phosphatidylcholine (PC) production rates as assayed by choline incorporation. We developed lipid isotope tracing analysis for zebrafish tumors and observed reductions in phosphatidylcholine synthesis by both the CDP-choline and PEMT pathways. The observed changes in the β-catenin-driven HCC phospholipidome suggest that zebrafish can recapitulate conserved features of HCC lipid metabolism and may serve as a model for identifying future HCC-specific lipid metabolic targets.
Topics: beta Catenin; Carcinoma, Hepatocellular; Zebrafish; Humans; Animals; Phosphatidylcholines; Liver Neoplasms; Lipid Metabolism; Animals, Genetically Modified; Phospholipids; Cell Line, Tumor; Lipidomics
PubMed: 38795827
DOI: 10.1016/j.bbalip.2024.159514 -
Cell Host & Microbe Jun 2024The extent to which bacterial lipids produced by the gut microbiota penetrate host tissues is unclear. Here, we combined mass spectrometry approaches to identify lipids...
The extent to which bacterial lipids produced by the gut microbiota penetrate host tissues is unclear. Here, we combined mass spectrometry approaches to identify lipids produced by the human gut symbiont Bacteroides thetaiotaomicron (B. theta) and spatially track these bacterial lipids in the mouse colon. We characterize 130 B. theta lipids by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using wild-type and mutant B. theta strains to confidently identify lipid structures and their interconnected pathways in vitro. Of these, 103 B. theta lipids can be detected and spatially mapped in a single MALDI mass spectrometry imaging run. We map unlabeled bacterial lipids across colon sections of germ-free and specific-pathogen-free (SPF) mice and mice mono-colonized with wild-type or sphingolipid-deficient (BTMUT) B. theta. We observe co-localization of bacterially derived phosphatidic acid with host tissues in BTMUT mice, consistent with lipid penetration into host tissues. These results indicate limited and selective transfer of bacterial lipids to the host.
Topics: Animals; Mice; Lipidomics; Bacteroides thetaiotaomicron; Gastrointestinal Microbiome; Colon; Lipids; Tandem Mass Spectrometry; Chromatography, Liquid; Lipid Metabolism; Germ-Free Life; Specific Pathogen-Free Organisms; Phosphatidic Acids; Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sphingolipids; Mice, Inbred C57BL; Female
PubMed: 38795710
DOI: 10.1016/j.chom.2024.04.021 -
Food Chemistry Oct 2024Enzymatic browning and microbial growth are two natural phenomena that occur when fruits and vegetables are exposed to abnormal conditions, i.e., temperatures in the...
Enzymatic browning and microbial growth are two natural phenomena that occur when fruits and vegetables are exposed to abnormal conditions, i.e., temperatures in the range of 12-22 °C, leading to their spoilage. Controlling the temperatures during the supply chain aims to optimize the product's shelf life. Irreversible thermochromic beads were fabricated using a simple extrusion technique containing fatty acid, lecithin, and anthocyanin solution-alginate. The pigmentation durability was adjusted based on electrostatic interactions, as evidenced by the reduction in dye leaching in the case of the produced bead at pH = 6 to less than 0.007 after 45 min. Characterization shows that the chosen combination of fatty acids and the quinonoid molecule is useful for producing thermochromic beads, with a color change at 12 °C-22 °C, from blue to purple. Using the prepared thermochromic beads in the supply chain of fresh-cut salad and brussels sprouts showed a great result for monitoring their freshness after 21 ± 1 min.
Topics: Lecithins; Fatty Acids; Food Packaging; Flavonoids; Vegetables; Fruit; Temperature
PubMed: 38795617
DOI: 10.1016/j.foodchem.2024.139698 -
The Journal of Physical Chemistry. B Jun 2024In this work, we explored how the amount of cholesterol in the lipid membrane composed of phosphatidylcholine (POPC) or phosphatidylglycerol (POPG) affects the...
In this work, we explored how the amount of cholesterol in the lipid membrane composed of phosphatidylcholine (POPC) or phosphatidylglycerol (POPG) affects the interaction with 1-dodecyl-3-methylimidazolium bromide ([CMIM]Br) ionic liquids using various biophysical techniques. On interacting with the membrane, [CMIM]Br leads to enhanced membrane permeability and induces membrane fusion, leading to an increase in vesicle size. The H-based solid-state NMR investigations of cholesterol-containing lipid membranes reveal that [CMIM]Br decreases the lipid chain order parameters and counteracts the lipid condensation effect of cholesterol to some extent. Therefore, as the amount of cholesterol in the membrane increases, the membrane effect of [CMIM]Br decreases. The effect of [CMIM]Br on the membrane properties is more pronounced for POPC compared to that of POPG membranes. This suggests a dependence of these effects on the electrostatic interactions, indicating that the influence of [CMIM]Br varies based on the lipid composition. The findings suggest that the presence of cholesterol can modulate the effect of [CMIM]Br on membrane properties, with variations observed between POPC and POPG membranes, highlighting the importance of lipid composition. In short, this study provides insights into the intricate interplay between cholesterol, the lipid membrane, and the ionic liquid [CMIM]Br.
Topics: Ionic Liquids; Cholesterol; Phosphatidylglycerols; Phosphatidylcholines; Imidazoles; Permeability; Lipid Bilayers
PubMed: 38795045
DOI: 10.1021/acs.jpcb.4c01531