Lipopolysaccharide toxin added to primary hepatocyte culture slightly modified the basal concentrations of (3)H-serine-labeled sphingomyelin, sphingosine, and ceramide. Ethanol reduced the levels of sphingomyelin and sphingosine by 20-25 and 15-20%, respectively, but increased ceramide content by 7-17%. Tumor necrosis factor reduced the concentrations of sphingomyelin and sphingosine, but did not modify the content of ceramide. Combined treatment with lipopolysaccharide toxin and ethanol potentiated the effect of alcohol.
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http://dx.doi.org/10.1007/s10517-009-0379-4 | DOI Listing |
Int J Mol Sci
January 2025
School of Biological Sciences and The Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Sphingolipidomic mass spectrometry has provided valuable information-and surprises-about sphingolipid structures, metabolism, and functions in normal biological processes and disease. Nonetheless, many noteworthy compounds are not routinely determined, such as the following: most of the sphingoid bases that mammals biosynthesize de novo other than sphingosine (and sometimes sphinganine) or acquire from exogenous sources; infrequently considered metabolites of sphingoid bases, such as N-(methyl)-derivatives; "ceramides" other than the most common N-acylsphingosines; and complex sphingolipids other than sphingomyelins and simple glycosphingolipids, including glucosyl- and galactosylceramides, which are usually reported as "monohexosylceramides". These and other subspecies are discussed, as well as some of the circumstances when they are likely to be seen (or present and missed) due to experimental conditions that can influence sphingolipid metabolism, uptake from the diet or from the microbiome, or as artifacts produced during extraction and analysis.
View Article and Find Full Text PDFCurr Cancer Drug Targets
January 2025
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Radiotherapy stands as a cornerstone in cancer therapy, with nuclear DNA acknowledged as the principal target molecule for radiation-induced cellular demise or injury. Nonetheless, an expanding body of contemporary research elucidates the significant contri-bution of sphingolipids to radiation-induced cell death, particularly in modulating radiation-induced apoptosis. Radiation can instigate apoptosis through multiple pathways of sphin-golipid metabolism, encompassing the activation of ceramide synthase, acid sphingomyelin-ase, neutral sphingomyelinase, sphingosine-1-phosphate lyase, and sphingosine-1-phosphate phosphatase, and the inhibition of sphingosine kinase-1.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Department of Medical Biochemistry, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey.
The aim of this study was to determine the effect of Sparstolonin B (SsnB) on cell proliferation and apoptosis in human breast cancer (MCF-7) and human ovarian epithelial cancer (OVCAR-3) cell lines in the presence and absence of estradiol hemihydrate (ES). Phosphoinositol-3 kinase (PI3K), phosphorylated protein kinase B alpha (p-AKT), phosphorylated mTOR (mechanistic target of rapamycin) signaling proteins, and sphingomyelin/ceramide metabolites were also measured within the scope of the study. The anti-proliferative effects of SsnB therapy were evaluated over a range of times and concentrations.
View Article and Find Full Text PDFBiol Pharm Bull
January 2025
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Ceramide (Cer) is synthesized in the endoplasmic reticulum (ER) using sphinganine as the common backbone and is then transported to the Golgi apparatus to synthesize two complex sphingolipids, sphingomyelin (SM) and glucosylceramide (GlcCer). Brefeldin A (BFA) affects the structure of the Golgi apparatus, resulting in the redistribution of the Golgi proteins into the ER. Therefore, BFA has been used to examine the ER-to-Golgi trafficking of lipids, but the detailed lipid changes in cells upon BFA treatment are not fully understood.
View Article and Find Full Text PDFSci Rep
January 2025
MSD R&D Innovation Centre, 120 Moorgate, London, EC2M 6UR, UK.
Dysfunction of the endo-lysosomal intracellular Cholesterol transporter 2 protein (NPC2) leads to the onset of Niemann-Pick Disease Type C (NPC), a lysosomal storage disorder. Metabolic and homeostatic mechanisms are disrupted in lysosomal storage disorders (LSDs) hence we characterized a cellular model of NPC2 knock out, to assess alterations in organellar function and inter-organellar crosstalk between mitochondria and lysosomes. We performed characterization of lipid alterations and confirmed altered lysosomal morphology, but no overt changes in oxidative stress markers.
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