Intra- and intercellular trafficking in sphingolipid metabolism in myelination

In the last four decades, the emphasis was laid on the research of small organic molecules with potential anti-cancer activity. Linezolid was the first oxazolidinone derivative approved by FDA for MRSA treatment. Despite its major role in antimicrobial activity, these molecules display other properties, also serving as an antitumor agent. The importance of drug repurposing could be highlighted by the use of Oxazolidinone derivatives in pre-clinical studies, which are able to act through different pathways, such as partial agonist of transcription factor PPAR-γ, an inhibitor of key enzymes related to hormone-dependent disorders and even on sphingolipid metabolism as well. The purpose of this short review is to discuss the application of oxazolidinone derivatives as an antitumor agent by highlighting the most promising molecules studied by many research groups worldwide. Main biological activity against several tumor cell lines, including hematopoietic and solid cancer cell lines have been discussed. In addition, this study intends to report how different types of oxazolidinone derivatives can act as antitumor agents describing their distinct mechanisms of action based on their targets.

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Early-Onset Osteoporosis

Calcified Tissue International ◽

10.1007/s00223-021-00885-6 ◽

2021 ◽

Author(s):

Outi Mäkitie ◽

M. Carola Zillikens

Keyword(s):

Young Adults ◽

Early Onset ◽

Type I Collagen ◽

Young Patients ◽

Fragility Fractures ◽

Underlying Disease ◽

Bone Fragility ◽

Sphingolipid Metabolism ◽

Type I ◽

Loss Of Function

AbstractOsteoporosis is a skeletal disorder with enhanced bone fragility, usually affecting the elderly. It is very rare in children and young adults and the definition is not only based on a low BMD (a Z-score < − 2.0 in growing children and a Z-score ≤ − 2.0 or a T-score ≤ − 2.5 in young adults) but also on the occurrence of fragility fractures and/or the existence of underlying chronic diseases or secondary factors such as use of glucocorticoids. In the absence of a known chronic disease, fragility fractures and low BMD should prompt extensive screening for secondary causes, which can be found in up to 90% of cases. When fragility fractures occur in childhood or young adulthood without an evident secondary cause, investigations should explore the possibility of an underlying monogenetic bone disease, where bone fragility is caused by a single variant in a gene that has a major role in the skeleton. Several monogenic forms relate to type I collagen, but other forms also exist. Loss-of-function variants in LRP5 and WNT1 may lead to early-onset osteoporosis. The X-chromosomal osteoporosis caused by PLS3 gene mutations affects especially males. Another recently discovered form relates to disturbed sphingolipid metabolism due to SGMS2 mutations, underscoring the complexity of molecular pathology in monogenic early-onset osteoporosis. Management of young patients consists of treatment of secondary factors, optimizing lifestyle factors including calcium and vitamin D and physical exercise. Treatment with bone-active medication should be discussed on a personalized basis, considering the severity of osteoporosis and underlying disease versus the absence of evidence on anti-fracture efficacy and potential harmful effects in pregnancy.

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Conversion by rat brain preparation of lignoceric acid to ceramides and cerebrosides containing both alpha-hydroxy and nonhydroxy fatty acids. Effects of compounds which affect sphingolipid metabolism.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)50663-3 ◽

1979 ◽

Vol 254 (10) ◽

pp. 3840-3844

Author(s):

I Singh ◽

Y Kishimoto ◽

R R Vunnam ◽

N S Radin

Keyword(s):

Fatty Acids ◽

Rat Brain ◽

Lignoceric Acid ◽

Sphingolipid Metabolism

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Sex differences in the association of sphingolipids with age in Dutch and South-Asian Surinamese living in Amsterdam, the Netherlands

Biology of Sex Differences ◽

10.1186/s13293-020-00353-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mirthe Muilwijk ◽

Nardie Callender ◽

Susan Goorden ◽

Frédéric M. Vaz ◽

Irene G. M. van Valkengoed

Keyword(s):

Sex Differences ◽

Waist Circumference ◽

South Asian ◽

Plasma Concentrations ◽

Plasma Lipid ◽

Ethnic Origin ◽

Sphingolipid Metabolism ◽

Cvd Risk ◽

Men And Women ◽

Liquid Chromatography Tandem Mass

Abstract Background Men have a higher risk for cardiovascular disease (CVD) early in life, while women have a higher risk later in life. The sex-related differences in CVD risk, especially by age, could be related to sphingolipid metabolism. We compared plasma sphingolipid concentrations and its increase by age in men and women. Methods Plasma concentrations of 13 types of sphingolipids were measured by liquid chromatography-tandem mass spectrometry in a random subsample of 328 men and 372 women of Dutch and South-Asian Surinamese ethnic origin, participating in the HELIUS study. Sphingolipid concentrations were compared between men and women by age group (18–39, 40–55, and 56–70 years). Multiple linear regression was used to determine sex differences in age trends in sphingolipids stratified by ethnicity. Analyses were performed without adjustment and adjusted for body mass index (BMI) and waist circumference. Results At age 18–39 years, sphingolipid concentrations were lower in women than those in men, but at age 56–70 years this was reversed. At higher age, women showed higher concentrations than men. In line, we observed a more rapid increase of sphingolipid concentrations by age in women than in men. The observed sex differences were not explained by BMI or waist circumference. Patterns of sex differences were similar across ethnic groups, although the strength of associations differed. Conclusions Mean sphingolipid concentrations increase more rapidly with age in women than in men. Therefore, plasma lipid concentrations of sphingolipids, although lower in women than in men at younger age, are higher in women than in men at older age.

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