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Special Issue "Sphingolipid Metabolism and Signaling in Diseases"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editor

Prof. Dr. Paola Giussani
Website
Guest Editor
Department of Medical Biotechnology and Translational Medicine, 20090 Segrate (MI), Italy
Interests: Sphingolipids; sphingosine-1-phosphate; ceramide; signaling; cancer; multiple sclerosis

Special Issue Information

Dear Colleagues,

It is now well known that sphingolipids are not only ubiquitous components of cell membranes but also have emerged as bioactive molecules involved in the control of cell fate. Sphingolipids have been shown to be involved in signal transduction and, consequently, in the regulation of a huge number of physiological and pathophysiological processes such as cell proliferation, survival, death, differentiation, migration, and invasiveness. The dysregulation of sphingolipid metabolism and signaling is associated with and contributes to the pathogenesis of numerous pathologies, including inflammation, cancer, diabetes, neurodegenerative diseases, and cystic fibrosis. The control of sphingolipid levels can be achieved through the regulation of specific enzymes of their metabolism as well as of the specific transporters or receptors involved in their transport within or outside the cells. The exact molecular mechanisms mediated by sphingolipids to modulate the cellular effects are still not completely understood, and new knowledge on the metabolism and signaling of sphingolipids will help in further understanding the role of sphingolipids in a variety of physiopathological conditions.

For the Special Issue “Sphingolipids Metabolism and Signaling in Diseases”, we welcome your contributions in the form of original research and review articles on all aspects of sphingolipids and their role in physiological and pathophysiological metabolic processes.

Prof. Dr. Paola Giussani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sphingolipids
  • sphingosine-1-phosphate
  • ceramide
  • sphingolipid-mediated signaling
  • cancer
  • neurodegenerative diseases
  • inflammatory diseases
  • diabetes
  • cystic fibrosis

Published Papers (2 papers)

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Research

Open AccessArticle
A Bioassay Using a Pentadecanal Derivative to Measure S1P Lyase Activity
Int. J. Mol. Sci. 2021, 22(3), 1438; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031438 - 01 Feb 2021
Abstract
Sphingosine-1-phosphate (S1P) is a unique lipid ligand binding to S1P receptors to transduce various cell survival or proliferation signals via small G proteins. S1P lyase (S1PL) is the specific enzyme that degrades S1P to phosphoethanolamine and (2E)-hexadecenal and therefore regulates S1P levels. S1PL [...] Read more.
Sphingosine-1-phosphate (S1P) is a unique lipid ligand binding to S1P receptors to transduce various cell survival or proliferation signals via small G proteins. S1P lyase (S1PL) is the specific enzyme that degrades S1P to phosphoethanolamine and (2E)-hexadecenal and therefore regulates S1P levels. S1PL also degrades dihydrosphingosine-1-phosphate (Sa1P), with a higher affinity to produce hexadecanal. Here, we developed a newly designed assay using a C17-Sa1P substrate that degrades into pentadecanal and phosphoethanolamine. For higher sensitivity in pentadecanal analysis, we developed a quantitative protocol as well as a 5,5-dimethyl cyclohexanedione (5,5-dimethyl CHD) derivatization method. The derivatization conditions were optimized for the reaction time, temperature, and concentrations of the 5,5-dimethyl CHD reagent, acetic acid, and ammonium acetate. The S1PL reaction in the cell lysate after spiking 20 µM of C17-Sa1P for 20 min was linear to the total protein concentrations of 50 µg. The S1PL levels (4 pmol/mg/min) were readily detected in this HPLC with fluorescence detection (λex = 366 nm, λem = 455 nm). The S1PL-catalyzed reaction was linear over 30 min and yielded a Km value of 2.68 μM for C17-Sa1P. This new method was validated to measure the S1PL activity of mouse embryonal carcinoma cell lines of the standard cell (F9-0), S1PL knockdown cells (F9-2), and S1PL-overexpressed cells (F9-4). Furthermore, we treated F9-4 cells with different S1PL inhibitors such as FTY720, 4-deoxypyridoxine (DOP), and the deletion of pyridoxal-5-phosphate (P5P), an essential cofactor for S1PL activity, and observed a significant decrease in pentadecanal relative to the untreated cells. In conclusion, we developed a highly sensitive S1PL assay using a C17-Sa1P substrate for pentadecanal quantification for application in the characterization of S1PL activity in vitro. Full article
(This article belongs to the Special Issue Sphingolipid Metabolism and Signaling in Diseases)
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Open AccessArticle
A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes
Int. J. Mol. Sci. 2020, 21(21), 8371; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218371 - 08 Nov 2020
Abstract
Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation [...] Read more.
Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naïve CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis. Full article
(This article belongs to the Special Issue Sphingolipid Metabolism and Signaling in Diseases)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Sphingolipid metabolism in cancers
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