International Journal of Molecular Sciences

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Special Issue Information

Dear Colleagues,

For 40 years, phospholipids were a forgotten area of investigation. In the last five years, however, this has changed. This Special Issue aims to review the role of phosphodiesters in metabolism and health. We now know that sphingomyelins are important to our understanding of brain fog due to Alzheimer’s dementia or infection with HIV or SAR-COV-2. Steroid phospho-diesters have a key role in potassium regulation during pregnancy, essential hypertension, and PTSD. Both sphingosines and steroids can be attached to either phosphoethanolamine or phosphocholine diesters. However, both ethanolamine and choline are required nutrients, and the phosphoesters must be synthesized, in situ, perhaps from CDP-serine or phosphatidyl-serine. As the guest editor of this Special Issue, I welcome research papers, reviews, and novel concepts for the synthesis and metabolism of phospholipids and sphingolipids.

Dr. María De La Luz Cádiz-Gurrea
Dr. Chasalow Fred
Guest Editors

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Keywords

spiral steroids
endogenous potassium sparing diuretics
sphingomyelin

Published Papers (2 papers)

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Research

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14 pages, 2080 KiB

Open AccessArticle

Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation

by Lisa A. G. Barth, Michèle Nebe, Hermann Kalwa, Akhil Velluva, Stephanie Kehr, Florentien Kolbig, Patricia Prabutzki, Wieland Kiess, Diana Le Duc, Antje Garten and Anna S. Kirstein

Int. J. Mol. Sci. 2022, 23(17), 9787; https://doi.org/10.3390/ijms23179787 - 29 Aug 2022

Cited by 2 | Viewed by 2375

Abstract

Phospholipid scramblase 4 (PLSCR4) is a member of a conserved enzyme family with high relevance for the remodeling of phospholipid distribution in the plasma membrane and the regulation of cellular signaling. While PLSCR1 and -3 are involved in the regulation of adipose-tissue expansion, the role of PLSCR4 is so far unknown. PLSCR4 is significantly downregulated in an adipose-progenitor-cell model of deficiency for phosphatase and tensin homolog (PTEN). PTEN acts as a tumor suppressor and antagonist of the growth and survival signaling phosphoinositide 3-kinase (PI3K)/AKT cascade by dephosphorylating phosphatidylinositol-3,4,5-trisphosphate (PIP3). Patients with PTEN germline deletion frequently develop lipomas. The underlying mechanism for this aberrant adipose-tissue growth is incompletely understood. PLSCR4 is most highly expressed in human adipose tissue, compared with other phospholipid scramblases, suggesting a specific role of PLSCR4 in adipose-tissue biology. In cell and mouse models of lipid accumulation, we found PLSCR4 to be downregulated. We observed increased adipogenesis in PLSCR4-knockdown adipose progenitor cells, while PLSCR4 overexpression attenuated lipid accumulation. PLSCR4 knockdown was associated with increased PIP3 levels and the activation of AKT. Our results indicated that PLSCR4 is a regulator of PI3K/AKT signaling and adipogenesis and may play a role in PTEN-associated adipose-tissue overgrowth and lipoma formation. Full article

(This article belongs to the Special Issue Phospholipids, Phosphosteroids and Sphingolipids in Metabolism and Health)

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Review

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22 pages, 5971 KiB

Open AccessReview

An Introduction to Spiral Steroids

by Fred Chasalow

Int. J. Mol. Sci. 2022, 23(17), 9523; https://doi.org/10.3390/ijms23179523 - 23 Aug 2022

Cited by 1 | Viewed by 1216

Abstract

In addition to classical steroids, which have cholesterol as a precursor, there are steroids with 7-dehydrocholesterol as a precursor. This review describes the identification of these steroids, their biosynthesis, and some aspects of their function. There are three classes of these compounds, distinguished by the number of their carbon atoms, 23, 24, and 25. Each class has a spiral steroid and is a phosphodiester. Up until these investigations, no spiral steroids or steroid phosphodiesters were known. There are at least 13 compounds, of which six have been purified to near homogeneity; each one has been characterized by its mass and proposed composition, and they function by regulating the NaK-ATPase. Based on the tissues in which they have been detected, each class of compound seems to regulate a different isoform of the NaK-ATPase. This is an important site of endocrine regulation. Full article

(This article belongs to the Special Issue Phospholipids, Phosphosteroids and Sphingolipids in Metabolism and Health)

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