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Magnesium deficiency upregulates serine palmitoyl transferase (SPT 1 and SPT 2) in cardiovascular tissues: relationship to serum ionized Mg and cytochrome c.

The present work tested the hypothesis that a short-term dietary deficiency of magnesium (Mg) (21 days) in rats would result in the upregulation of the two major subunits of serine palmitoyl-CoA-transferase, serine palmitoyl transferase (SPT 1) and SPT 2 (the rate-limiting enzymes responsible for the de novo biosynthesis of ceramides) in left ventricular, right ventricular, and atrial heart muscle and abdominal aortic smooth muscle, as well as induce a reduction in serum sphingomyelin concomitant with the release of mitochondrial cytochrome c (Cyto c) in these tissues. Our data indicate that s…

Anti-microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris.

Lipids are important constituents of the human epidermis. Either free and organized into broad lipid bilayers in the intercorneocytes spaces, or covalently bound to the corneocyte envelope, they play a crucial role in permeability barrier function and are major contributors to cutaneous anti-microbial defense. Free sphingoid bases are a recent addition to this family of active lipids, which emerged from studies of breakdown products from ceramides. Phytosphingosine (PS) is a lipid occurring naturally in the stratum corneum, both in its free form and as a part of the major fraction of ceramides…

Carbohydrate structures of three novel phosphoinositol-containing sphingolipids from the yeast Histoplasma capsulatum.

From the yeast phase of the human pathogen Histoplasma capsulatum, three novel glycolipids were isolated, shown to react with sera from histoplasmosis patients, and partially characterized: compound V, ceramide-P-inositol-[mannose2]; compound VI, ceramide-P-inositol-[mannose2, galactose]; compound VIII, an isomer of compound VI [Barr, K., & Lester, R.L. (1984) Biochemistry (preceding paper in this issue)]. Ammonolysis of these lipids has yielded all the carbohydrate (oligosaccharides V, VI, and VIII) as novel, intact oligosaccharides suitable for characterization. Anomeric configurations were

Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy.

INTRODUCTION: Interleukin (IL)-18 is involved in regulation of lipid and glucose metabolism. Mice lacking whole-body IL-18 signalling are pr … ere obtained and IL-18 and IL-18R mRNA expression were measured by real-time PCR and sphingolipids (ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by HPLC. Insulin resistance was assessed by HOMA and the insulin response during an OGTT. RESULTS: Patients with HIV-LD had a 60% and 54% lower level of muscular IL-18 and IL-18R mRN …

Neuroprotective role of sphingolipid rheostat in excitotoxic retinal ganglion cell death.

The glutamate excitotoxicity has been suggested as a factor involved in the loss of retinal neuronal cells, including retinal ganglion cell (RGC), in various retinal degenerative diseases including ischemia-reperfusion injury, diabetic retinopathy, and glaucoma. Excitotoxic RGC death is caused not only by direct damage to RGCs but also by indirect damage due to the inflammation of retinal glial cells. Sphingosine 1-phosphate (S1P) and ceramides are bioactive sphingolipids which have been shown to possess important physiological roles in cellular survival and apoptosis, and the balance between …

Developmental bisphenol A exposure alters adipose metabolism and lipid remodeling in female mouse offspring.

Bisphenol A (BPA), an endocrine-disrupting chemical widely detected in human populations, has been implicated in metabolic disorders following early-life exposure. However, the long-term effects of developmental BPA exposure on adipose metabolism under post-weaning dietary challenge remain incompletely understood. Pregnant C57BL/6J mice received BPA in drinking water at a maternal nominal target exposure of 50 μg/kg/day from gestational day 6 to postnatal day 21. After weaning, offspring were fed a normal diet or high-fat diet and evaluated at PND22, PND36, and PND91. Body weight, adipose morp

Infectious spleen and kidney necrosis virus promotes replication organelle formation and sphingolipid biosynthesis to facilitate viral replication.

Infectious spleen and kidney necrosis virus (ISKNV) is a highly pathogenic iridovirus that causes severe economic losses in aquaculture. Viruses usually remodel host lipid metabolism to facilitate their replication. However, whether ISKNV modulates host lipid metabolism to support its infection remains unknown. In this study, using lipidomics analysis, we found that ISKNV infection induced widespread upregulation of host lipid profiles, including glycerophospholipids, glycerolipids, and sphingolipids. Transcriptional analysis revealed coordinated regulation of key metabolic enzymes, collective

Glucosylceramide Synthase, a Key Enzyme in Sphingolipid Metabolism, Regulates Expression of Genes Accounting for Cancer Drug Resistance.

Emergent cancer drug resistance and further metastasis can mainly be attributed to altered expression levels and functional activities of multiple genes of cancer cells under chemotherapy. In response to challenge with anticancer drugs, enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) confers drug resistance and enrichment with cancer stem cells. p53 mutations, which gain function in tumor progression, are prevalently extant in ovarian cancers. Via integrated gene expression assessments, we characterized GCS-responsive genes in ovarian cancer cells treated with dact

Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply.

A mechanistic understanding of how intracellular pathogens evade the intrinsic defenses of their host cells could open up intriguing therapeutic opportunities. Here, we applied a genome-wide genetic screening approach to investigate the nature of the defensive host cell death response suppressed by the membrane trafficking modulator CpoS, an effector protein secreted by the obligate intracellular bacterial pathogen Chlamydia trachomatis. Initially, this work revealed a CpoS-deficient mutant to exhibit a markedly increased dependence on host cellular synthesis of ceramides, the precursors of co…

Множественный метод ЛК-МС/МС для количественной оценки 14 сфинголипидов в организме человека с цереброспином (CSF).

Сфинголипиды представляют собой биоактивные липиды, состоящие из сфингоидной основы, связанной с различными длинноцепными толстыми кислотами и фосфохолином, и в некоторых случаях могут также содержать один или несколько сахаров. Несколько видов сфинголипидов имеют схожие структуры и даже могут иметь идентичный химический состав, но различаются по своей биологической функции. По этой причине их можно точно определить только с использованием жидкой хроматографии в сочетании с масс-спектрометрией (LC-MS). Этот метод может отделять сфинголипиды на основе их гидрофобии и давать количественную оценк

Совпадение в аннотации оригинала
Sphingolipids are bioactive lipids comprised of a sphingoid base linked to various long-chain fatty acids and phosphocholine and, in some ca … , we describe the development of a new LC-MS method to measure 14 sphingolipid species, including 7 ceramides (C14, C16, C18, C20, C24, C18:1, C24:1), 4 glycosphingolipids (C16 Glucosyl(ß) Ceramide (d18:1/16:0, C16 Galactosyl(ß) Ceramide (d18:1/16:0), C16 Lac Cer, C18 Lac Cer) and 3 sphingosines (Sphingosine (Sph), Glucosyl(ß) Sphingosine (d18:1), Galactosy …

Human Brain Lipidomics: Utilities of Chloride Adducts in Flow Injection Analysis.

Ceramides have been implicated in a number of disease processes. However, current means of evaluation with flow infusion analysis (FIA) have been limited primarily due to poor sensitivity within our high-resolution mass spectrometry lipidomics analytical platform. To circumvent this deficiency, we investigated the potential of chloride adducts as an alternative method to improve sensitivity with electrospray ionization. Chloride adducts of ceramides and ceramide subfamilies provided 2- to 50-fold increases in sensitivity both with analytical standards and biological samples. Chloride adducts o…

N-butyldeoxynojirimycin treatment restores the innate fear response and improves learning in mucopolysaccharidosis IIIA mice.

UNLABELLED: Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and the secondary neuronal storage of gangliosides GM2 and GM3 in the brain. GM2 storage is associated with CNS deterioration in the GM2 gangliosidosis group of lysosomal storage disorders and may also contribute to MPS CNS disease. N-butyldeoxynojirimycin, an inhibitor of ceramide glucosyltransferase activity and therefore of ganglio

Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.

UNLABELLED: Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus-induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lun

The roles of sphingosine kinase 1 and 2 in regulating the metabolome and survival of prostate cancer cells.

We have previously shown that treatment of androgen-sensitive LNCaP cells with the sphingosine kinase (SK) inhibitor SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole) induces the proteasomal degradation of two N-terminal variants of SK1 (SK1a and SK1b), increases C22:0-ceramide and diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) and reduces S1P levels, and promotes apoptosis. We have now investigated the effects of three SK inhibitors (SKi, (S)-FTY720 vinylphosphonate, and (R)-FTY720 methyl ether) on metabolite and sphingolipid levels in androgen-sensitive LNCaP and androgen-independent LNCa

Effect of Loxosceles gaucho venom on cell morphology and behaviour in vitro in the presence and absence of sphingomyelin.

This study was performed to investigate whether the toxic effects of Loxosceles gaucho venom on cells might be exerted via stimulators of TNF-alpha release generated by sphingomyelinase D--a major component of the venom. It was demonstrated that L. gaucho venom alone is unable to induce TNF-alpha release by J774A.1 cells, while in the presence of exogenous sphingomyelin it induces a high level of TNF-alpha release which is significantly increased by incubation with non-inactivated serum. Ceramide phosphate also induces TNF-alpha release in J774A.1 cells, but (unlike sphingomyelin/sphingomyelin

Bcl-2 and mitochondrial oxygen radicals. New approaches with reactive oxygen species-sensitive probes.

Investigations into the capacity of the Bcl-2 protein to prevent apoptosis have targeted mitochondria as key sites of the preventative action accorded by Bcl-2 to cells. Using novel approaches with fluorescence probes and autofluorescence detection of endogenous NAD(P)H, we have examined the effects of expressing Bcl-2 in the Bcl-2 negative Burkitt's lymphoma cell line Daudi. We evaluated for the first time the effect of Bcl-2 expression on the intracellular distribution and production of hydrogen peroxide, under basal conditions and after treatment with apoptosis inducing agents, ceramide ana

CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.

The classical paradigm of the sphingolipid rheostat-balancing pro-apoptotic ceramide against pro-survival sphingosine-1-phosphate-has evolved into a complex signaling landscape where N-acyl chain length serves as the fundamental determinant of biological outcomes. This perspective explores the pivotal role of ceramide synthase 2 (CerS2) in synthesizing very-long-chain (VLC) ceramides (C22-C26) and its function as a central regulator of cellular stress responses. While CerS2 typically acts as a tumor suppressor, its activity is frequently attenuated in aggressive malignancies through alternativ…

Plasma lipidome mediates the causal effect of chronic hepatitis B on cirrhosis: A Mendelian randomization study.

This study aimed to investigate the role of the plasma lipid species in the progression from chronic hepatitis B (CHB) infection to cirrhosis. We conducted 2-sample Mendelian randomization (MR) and genome-wide mediation analyses to explore the causal relationship between CHB and cirrhosis, focusing on lipid species as potential mediators. The inverse variance weighted method was used as the primary analytical approach, supported by complementary estimators. Sensitivity analyses - including Cochran's Q test, MR-Egger intercept test, of Mendelian randomization pleiotropy residual sum and outlier

Differential Effects of Sphingolipids on Cell Death and Antioxidant Defenses in Type 1 and Type 2 Endometrial Cancer Cells.

Endometrial cancer (EC) is classified into two main subtypes with distinct molecular profiles. Sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), are crucial regulators of cell survival, apoptosis, and oxidative stress. This study examined the impact of sphingolipid metabolism in Ishikawa (type 1) and HEC-1A (type 2) EC cells following the silencing of Sptlc1 and Sptlc2, which encode subunits of serine palmitoyltransferase (SPT), a key enzyme in de novo sphingolipid synthesis. Gene silencing was confirmed by RT-PCR and Western blot, while sphingolipid levels were quantifie

Lipid profiles of patients with manifest coronary versus peripheral atherosclerosis - Is there a difference?

AIM: Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins a … not differ significantly between patients with PAD and CAD. Applying ratios and scores derived from ceramides and phosphatidylcholines further improved the discrimination between PAD and CAD. These significant differences were independent of body composition, from the status of smoking or type 2 diabetes mellitus, and also from apolipoprotein C-III and othe …