Metabolism: Therapeutic Bone Marrow Transplantation in Niemann-Pick Mice

Mice with Niemann-Pick disease were treated with bone marrow transplantation. The loss of Purkinje cells remained unchanged, but the accumulation of sphingomy elin and cholesterol was reduced in the visceral organs, especially in the spleen, three weeks after marrow graft. The activity of acid sphingomyelinase was increased in the grafted liver of mice, and in the spleen this activity was elevated to normal levels.     

New insights into renal lipid dysmetabolism in diabetic kidney disease

Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs, including the kidney. Research suggests that impaired cholesterol metabolism, increased lipid uptake or synthesis, increased fatty acid oxidation, lipid droplet accumulation and an imbalance in biologically active sphingolipids (such as ceramide, ceramide-1-phosphate and sphingosine-1-phosphate) contribute to the development of diabetic kidney disease (DKD). Currently, the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production, oxidative stress, inflammation, or cell death. Therefore, control of renal lipid dysmetabolism is a very important therapeutic goal, which needs to be archived. This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.     

尼曼-匹克病B型的产前诊断

目的对尼曼－匹克病Ｂ型进行产前诊断。方法应用成色底物２－己癸酰氨基－４－硝基苯磷酸胆碱，对４例尼曼－匹克病Ｂ型先证者及其父母进行了外周血白细胞中鞘磷脂酶的酶学分析，并对这４例先证者再妊娠的母亲进行了绒毛、羊水细胞中的酶学分析。结果先证者均有明显的鞘磷脂酶的缺乏，而父母的酶水平与正常有重叠。对２例先证者母亲孕早期绒毛、孕中期羊水进行酶学分析，结果与正常个体差异均无显著意义，另外２例仅于孕中期作了羊水细胞中的酶学分析，结果亦正常。随访４名先证者母亲所生新生儿表型正常。结论绒毛和羊水细胞中鞘磷脂酶分析可用于尼曼－匹克病的产前诊断。     

Niemann-Pick disease type C

Summary A complex neuropathological study of two cases of Niemann-Pick disease (NPD) type C (NPDC) revealed some novel features in the chemical pathology of the neuronal storage. Lipid histochemistry showed the presence of a lipid which met the criteria of a neuronal glycosphingolipid. Sphingomyelin (SM) was not detected in the neurones in any of the regions examined. Lipid chemical analysis of total extracts and of partially purified lysosomal fraction of the brain cortex showed markedly increased levels of neutral ceramide hexosides especially of glucosylceramide and ceramide dihexoside (mostly of its slower band). Phospholipids were not significantly increased. Monosialogangliosides GM₂ and GM₃ were increased only slightly. The storage process displayed the well known fine structure and was accompanied by a marked secondary increase in some lysosomal enzyme activities. There was neuroaxonal dystrophy (NAD) of considerable intensity and extent. Many spheroids contianed masses of degenerated organelles and neurofilaments in various proportions and displayed variable activities of acid phosphatase, nonspecific esterase and dehydrogenases. There was marked brain atrophy accompanied in one case by severe demyelination. Enzyme studies revealed partial decrease of sphingomyelinase (SMase) and betaglucosidase activities in cultured fibroblasts, as well as lack of cathodic SMase activity on isoelectric focusing. No defects of these enzymes were found in the brain samples. The findings are regarded as significant since they indicate a biochemical defect in which SM is not primarily involved and which may thus be fundamentally different from that in type A of NPD.     

Very Long-Chain Fatty Acids in Erythrocyte Membrane Phospholipids in Adrenoleukodystrophy

Mass fragmentography was used to analyze the very longchain fatty acid (VLCFA) composition of erythrocyte membrane phospholipids. The VLCFA content decreased in the order sphingomyelin (SM), phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The tetracosanoic acid (C24:0) and hexacosanoic acid (C26:0) content of both SM and PC in patients with adrenoleukodystrophy (ALD) were significantly higher than those in controls. The VLCFA content of PE was too small, in comparison with those of SM, to be accurately determined. ( Acta Paediatr Jpn 1989;31: 136–143)     

Niemann-Pick disease type C with enhanced glycolipid storage

Summary A case of infantile neurovisceral disease was classified according to the morphological and chemical analysis of fixed tissue as a chemically different type of Niemann-Pick disease (NPD) type C, with glycolipids dominating the storage process. The diagnosis was reached on the basis of massive accumulation of neutral glycolipids in visceral storage elements (hepatocytes and macrophages) as an outstanding feature of lipid histochemistry. Chemical lipid analysis corroborated the findings by detecting a manyfold increase of glucosyl ceramide, lactosyl ceramide, ceramide trihexoside and GM₃ ganglioside. In addition, macrophages contained variable quantities of sphingomyelin. The brain showed slightly increased quantities of lactosylceramide (Slower fraction) and glucosyl ceramide. Apart from the classical neuronal storage changes there was also marked neuroaxonal dystrophy. In terms of quality, the glycolipid spectrum was comparable to that of NPD type C, in terms of quantity, the changes were consistent with those in so-called lactosyl-ceramidosis, which, however, was reclassified as NPD type C only recently. In our view, the present case is the second published observation of lactosylceramidosis classifiable as a glycolipid (GL) variety of NPD type C in which the normally considerable tendency to glycolipid storage is further enhanced while the storage of sphingomyelin is less expressed.     

Isolation, properties and partial amino acid sequence of a new actinoporin from the sea anemone Radianthus macrodactylus.

A new cytolytic toxin, actinoporin RTX-S II, was isolated from the sea anemone Radianthus macrodactylus with a high degree of purity by a combination of gel filtration, ion-exchange and reverse-phase chromatography. RTX-S II has molecular mass of 19,280 Da and isoelectric point of 10.0. The hemolytic activity of RTX-S II is inhibited by sphingomyelin. RTX-S II had an LD(50) of 70 mg/kg, and is lacking in phospholipase activity. The amino acid composition of this protein contains a high amount of basic and non-polar amino acids and no cysteine. The N-terminal sequence of RTX-S II was determined. The partial amino acid sequence (141 aa) of RTX-S II was deduced based on the cDNA sequence obtained with two oligonucleotides encoding the N-terminal portion of RTX-S II and the internal conserved cytolysin peptide by PCR. A comparison of the RTX-S II cDNA sequence and the rtx-s II gene obtained with the same PCR primers indicates that they are 100% identical at the nucleotide level. It shows that no introns are present in the corresponding region of the rtx-s II gene. Multiple alignments of RTX-S II with known sequences of actinoporins show that RTX-S II is highly homologous to magnificalysin II from Heteractis magnifica. The predicted secondary structure of RTX-S II is predominantly anti-parallel beta-structure, which is in good agreement with experimental data obtained from other sea anemones-actinoporins.     

羊水样本卵磷脂和鞘磷脂检测超高效液相色谱串联质谱方法的建立及应用

目的建立检测羊水中卵磷脂和鞘磷脂(L/S)的超高效液相色谱串联质谱(UPLC-MS/MS)方法,以便准确、高效地预测胎儿肺成熟度。方法收集孕32~39周孕妇分娩时的羊水样本23份。依据新生儿Apgar评分标准,有3例胎儿胎肺未成熟、20例胎儿胎肺成熟。另收集孕18周孕妇羊水样本7份作为基线对照,建立检测羊水中卵磷脂和鞘磷脂水平的UPLC-MS/MS方法,计算卵磷脂/鞘磷脂(L/S)比值,同时采用板层小体计数(LBC)法检测板层小体(LB),评价2种方法在预测胎肺成熟度中的价值。结果建立的检测羊水中卵磷脂和鞘磷脂的UPLC-MS/MS方法精密度良好,离子峰强度和保留时间均在可检测范围内,主成分分析(PCA)显示6个质控样本聚类良好。以L/S比值=10作为判断胎肺成熟度与不成熟的临界值,UPLC-MS/MS的敏感性和特异性均为100%。以LB=50×10^9/L作为判断胎肺成熟度与不成熟的临界值,LBC法的敏感性和特异性分别为80%和95%。结论建立了检测羊水中卵磷脂和鞘磷脂水平的UPLC-MS/MS方法,其结果可靠,可以准确、高效地预测胎肺成熟度。     

Changes in plasma phospholipids and sphingomyelins with aging in men and women: A comprehensive systematic review of longitudinal cohort studies

BackgroundAging affects the serum levels of various metabolites which may be involved in the pathogenesis of chronic diseases. The aim of this review article is to summarize the relationship between aging and alterations in the plasma phospholipids and sphingomyelins.MethodsPRISMA guidelines were employed during all steps. MEDLINE (PubMed), Scopus, Embase and Web of Sciences databases and Google Scholar were searched up to October 2020. Cohort studies investigating the relationship between aging and within-person changes in sphingomyelin (SM), phosphatidyl choline (PC), lyso PC (LPC) and phosphatidyl ethanolamine (PE) were included. Newcastle-Ottawa scale was used to assess the quality of included studies.ResultsA total of 1425 studies were identified. After removing 610 duplicates and 723 irrelevant studies, full texts of 92 articles were evaluated. Of these 92, 6 studies (including data from 7 independent cohorts) met the inclusion criteria and are included in this review. All study populations were healthy and included both men and women. Results by sex were reported in 3 cohorts for PC, 5 cohorts for LPC, 3 cohorts for SM, and only 1 cohort for PE. In men, PC, SM, PE and LPC decreased with aging, although results for LPC were inconsistent. In women, LPC, SM, and PE increased age, whereas changes in PC were inconsistent.ConclusionWithin-person serum levels of phospholipids and sphingomyelins, decrease during aging in men and increase in women. Notably, however, there were some inconsistencies across studies of LPC in men and of PC in women.     

Effect of sphingomyelin and cholesterol on the interaction of St II with lipidic interfaces.

Sticholysin II (St II) is a cytolysin produced by the sea anemone Stichodactyla helianthus, characterized by forming oligomeric pores in natural and artificial membranes. In the present work the influence of the membrane lipidic components sphingomyelin (SM) and cholesterol (Cho) on binding and functional activity of St II, was evaluated using ELISA, lipid monolayers and liposomes. The aim of this work was to establish the promoting role of Cho and SM, both in St II binding and pore formation efficiency. In general the association (evaluated by ELISA and incorporation to phospholipid monolayers) of St II to lipids mixtures was better than to any one of the single components. Regarding the unique role of SM, it was found that, albeit inefficiently, St II binds to phosphatidylcholine (PC):Cho monolayers and liposomes, and is able to form active pores in these bilayers. The results in monolayers and liposomes show that the presence of SM and large amounts of Cho leads to the highest values of critical pressure and rate of association to monolayers, the most favorable interaction with liposomes, and the fastest rate of pore formation, in spite of the rigidity of the layers as suggested by the high generalized polarization (GP) of Laurdan incorporated to liposomes and FTIR data. Taken together, the present results show that the joint presence of SM and Cho, both in binary and ternary (PC containing) mixtures provide conditions particularly suitable for St II binding and function. We suggest that microdomains present in the bilayers could be important for toxin-membrane association.