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Resumen Los esfingolípidos (esfingomielina, glucolípidos y gangliósidos) se localizan en las membranas celulares, el plasma y las lipoproteínas. En pacientes con enfermedades cardiovasculares, renales y metabólicas, el perfil de los esfingolípidos y sus metabolitos (ceramida, esfingosina y esfingosina-1-fosfato) se modifica, y estos cambios pueden explicar las alteraciones en algunas respuestas celulares, como la apoptosis. Además, se ha sugerido que la esfingosina y la esfingosina-1-fosfato previenen la COVID-19. En esta revisión también se mencionan brevemente las técnicas que permiten el estudio de los esfingolípidos y sus metabolitos.
Abstract Sphingolipids (sphingomyelin, glycolipids, gangliosides) are located in cell membranes, plasma, and lipoproteins. In patients with cardiovascular, renal, and metabolic diseases, the profile of sphingolipids and their metabolites (ceramide, sphingosine, and sphingosine-1-phosphate) is modified, and these changes may explain the alterations in some cellular responses such as apoptosis. Furthermore, sphingosine and sphingosine-1-phosphate have been suggested to prevent COVID-19. This review also briefly mentions the techniques that allow us to study sphingolipids and their metabolites.
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Acid sphingomyelinase deficiency (ASMD), also known as type A and B Niemann-Pick disease, is a group of intra-lysosomal lipid storage diseases caused by mutations in the SMPD1 gene that decrease acid sphingomyelinase activity or even cause deletion, resulting in abnormal deposition of sphingolipids. This disease can be diagnosed by bone marrow aspiration, pathological biopsy, acid sphingomyelinase activity measurement and SMPD1 gene testing. In recent years, with the rapid progress of molecular diagnostic techniques, new insights have been gained in the laboratory diagnosis of ASMD by means of molecular genetic tests, biomarkers and acid sphingomyelinase activity assay. This article will review the diagnostic progress of ASMD, aiming to reduce the misdiagnosis and leakage of the disease and improve the clinicians′ understanding of the disease.
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Rituximab (RTX), as a monoclonal antibody of CD20 acting on B cell epitopes, has been applied to the field of kidney since 2005, and has become a research hotspot in the clinical treatment of glomerulonephritis. At present, in addition to its clinical safety and efficacy, some researchers are still committed to explore the mechanism of RTX in the treatment of renal diseases, trying to find out whether there is a specific target in renal tissue. In this paper, the mechanism of RTX in the treatment of focal segmental glomerulosclerosis is reviewed.
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Objective To investigate the roles of neutral sphingomyelinase-2 (nSMase2) pathway on cerebral edema and cerebral injury in cerebral ischemia-reperfusion injury in rats. Methods Seventy-six adult male SD rats were randomly divided into sham operation group (n = 12), modeling group (n = 16), vehicle group (n = 16), SB203580 (a p38 mitogen activated protein kinase [MAPK] inhibitor) treatment group (n = 16) , and MRS1754 (a selective adenosine A2B receptor [A2B AR] antagonist) treatment group (n = 16) according to the random number table. A suture-occluded method was used to induce a middle cerebral artery ischemia-reperfusion model. Vehicle, SB203580, and MRS1754 were injected into the lateral ventricles 30 min before model preparation, the neurological function score was performed after ischemia-reperfusion for 24 h. 2,3,5 triphenyltetrazolium staining was used to detect the infarct volume. The water content of brain tissue was detected by dry-wet weight method. Western blot analysis was used to detect the expression of nSMase 2 and p38 MAPK in ischemic brain tissue. Immunohistochemical staining was used to detect the expression of nSMase 2 in ischemic brain tissue. Results MRS1754 significantly decreased neurobehavioral score (P < 0. 05) and reduced cerebral infarction volume (P < 0. 05) in rats. Both MRS1754 and SB203580 significantly decreased the water content of ischemic brain tissue (all P < 0. 05). In addition, MRS1754 also significantly decrease the phosphorylation of p38 MAPK after ischemia-reperfusion and decreased the expression level of nSMase 2 (P < 0. 01). Conclusion Regulation of A2BAR and p38 MAPK of nSMase upstream may play a neuroprotective role after cerebral ischemia-reperfusion injury.
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Objective · To obtain the latest data on phospholipid composition of human milk in Shanghai and compare the differences in phospholipid composition at different lactation stages. Methods · Healthy postpartum women who delivered full-term infants in the Obstetrical Department of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between April and July, 2016 were enrolled. The colostrum, transitional milk, and mature milk were collected at Day 3, 10, and 45 after delivering babies, respectively. Human milk fat was extracted with Folch's method and phospholipids were separated with solid phase extraction (SPE). The phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin were quantitatively analyzed with HPLC/VWD. The differences in phospholipid composition at different lactation stages were compared with univariate analysis of variance and Games-Homell test. Results · One hundred women who provided at least one breast milk sample were enrolled. A total of 70 colostrum samples, 96 transitional milk samples, and 82 mature milk samples were collected. The total phospholipid content of mature milk [(281.93±118.54) μg/g] was significantly lower than that of colostrum [(381.99±205.90) μg/g]. At all lactation stages, the relative content of phosphatidylcholine was the highest (53.74%-59.36%), followed by sphingomyelin (28.12%-32.74%). The relative content of phosphatidylethanolamine was constant (P=0.617), the relative content of phosphatidylcholine gradually decreased (P=0.000), and that of sphingomyelin gradually increased (P=0.000) during the lactation. Conclusion · Sphingomyelin and phosphatidylcholine are major components of human milk phospholipids. The amount of phospholipids varies during the lactation. The total amount of phospholipids is lower in mature milk than in colostrum and transitional milk. The relative content of phosphatidylethanolamine is consistent at all lactation stages, the relative content of phosphatidylcholine gradually decreases, and that of sphingomyelin gradually increases.
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Our understanding of the functions of neutral sphingomyelinase (N-SMase) signaling has advanced over the past decade. In this review, we focus on the roles and regulation of N-SMase 1, N-SMase 2, N-SMase 3, an enzyme that generates the bioactive lipid ceramide through the hydrolysis of the membrane lipid sphingomyelin. A large body of work has now implicated N-SMase 2 in a diverse set of cellular functions, physiological processes, and disease pathologies. We focus on different aspects of this enzyme's regulation from transcriptional, post-translational, and biochemical. Furthermore, we expected N-SMase involvement in cellular processes including inflammatory signaling, cell growth, apoptosis, and tumor necrosis factor which in turn play important roles in pathologies such as cancer metastasis, variable disease, and other organ system disorders. Lastly, we examine avenues where targeted N-SMase inhibition may be clinically beneficial in disease scenarios.
Subject(s)
Apoptosis , Breast Neoplasms , Hydrolysis , Membranes , Neoplasm Metastasis , Pathology , Physiological Phenomena , Sphingomyelin Phosphodiesterase , Tumor Necrosis Factor-alphaABSTRACT
The goal of the present study is to elucidate the mechanism of quercetin on modulating Naja naja atra phospholipase A2 (PLA2) activities. Sphingomyelin inhibited PLA2 enzymatic activity and membrane-damaging activity against egg yolk phosphatidylcholine (EYPC), while cholesterol and quercetin abrogated the sphingomeyelin inhibitory effect. Quercetin incorporation led to a reduction in PLA2 enzymatic activity and membrane-damaging activity toward EYPC/sphingomyelin/cholesterol vesicles. Both cholesterol and quercetin increased detergent resistance and reduced membrane fluidity of EYPC/sphingomyelin vesicles. Quercetin reduced detergent insolubility but increased ordered lipid packing of EYPC/sphingomyelin/cholesterol vesicles. Acrylamide quenching studies and trinitrophenylation of Lys residues revealed that quercetin altered the membrane-bound mode of PLA2 differently upon absorption onto the membrane bilayers of different lipid compositions. However, 8-anilinonaphthalene sulphonate-binding assay revealed that quercetin marginally affected the interaction between active site of PLA2 with phospholipid vesicles. Collectively, our data indicate that membrane-inserted quercetin modulates PLA2 interfacial activity and membrane-damaging activity via its effects on membrane structure and membrane-bound mode of PLA2.
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Acid sphingomyelinase (ASM) is one enzyme responsible for the production of ceramide via the hydrolysis of sphingomyelin.Recent findings have revealed the important role of ASM in the initiation of ceramide-induced cell apoptosis,as well as in the pathophysiology of many common diseases (e.g.cardiovascular diseases,diabetes,pulmonary diseases,and neurological diseases).Other studies have also shown that ASM activation may occur through the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS),as well as by inflammatory mechanisms that may be induced by environmental and occupational stresses.ASM activation,in turn,may create excess or abnormally distributed ceramides,which could lead to tissue and organ injuries,including to the pulmonary,liver,kidney,and nervous systems.This review will discuss the basic biology of ASM and focus on the role and regulation of ASM in environmental stress responses.We propose that ASM activation is an important factor in environmental health,and that ASM-based therapeutics may have a key role in preventing environmental-induced tissue injury.
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As an important lipid in cell membrane and lipoprotein,sphingomyelin(SM)has widespread and considerable biological functions.It has close relation to the occurrence and development of atherosclerosis(AS),and the change of its concentration has become a seperate risk of atherosclerosis.Sphingomyelin synathase(SMS),the key enzyme in synthesis of SM,might become a new target for treatment of AS because of its expression and activity could directly influence the pathophysilogical process of AS.Here the recent reports about the structure and biological functions of SMS are summarized,and its role in AS and the possibilities of it being a potential drug target for AS therapy are reviewed.