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Editorial Board Members’ Collection Series: Advances in Sphingolipids
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Editorial Board Members’ Collection Series: Advances in Sphingolipids

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

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 6840

Special Issue Editors

Prof. Dr. Sandro Sonnino

E-Mail Website
Guest Editor
Department of Medical Biotechnology and Translational Medicine, University of Milano, 20054 Segrate, MI, Italy
Interests: gangliosides; Parkinson’s disease; mebrane organization; complex lipids; sphingosine; ceramide
Special Issues, Collections and Topics in MDPI journals
Dr. Paola Giussani

E-Mail Website
Guest Editor
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, LITA Segrate, Via Fratelli Cervi, 93, 20090 Segrate, Italy
Interests: sphingolipids; sphingosine-1-phosphate; ceramide; signaling; cancer; multiple sclerosis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jin-ichi Inokuchi

E-Mail Website
Guest Editor
Forefront Research Center, Graduate School of Science, Osaka University, Suita 565-0871, Osaka, Japan
Interests: glycosphingolipids; glucose metabolism; lipid; encephalomyelitis

Special Issue Information

Dear Colleagues,

Sphingolipids are a large class of cell membrane amphiphilic components; however, they have also emerged as bioactive molecules. They contain a rigid lipid moiety characterized by the presence of the sphingosine. The structure of sphingolipids varies from the high-molecular-mass polisialylated glycosphingolipids to sphingomyelin and simple ceramides, sphingosines and their phosphorylated derivatives.

The determination of their structure was challenging and required over 50 years from the first information of their presence in the human brain. Nevertheless, after several decades of research and the involvement of many groups, the role played by sphingolipids in maintaining cell physiology is now becoming increasingly clear.

Depending on their structure, sphingolipids are involved in different processes, both physiological and pathological. Sphingolipids are necessary for correct neuronal development, maintaining interactions with cell surface proteins necessary for the modulation of a variety of cell signaling processes.  On the other hand, their incorrect metabolism leads to serious neurodegenerative diseases, inflammation processes, cancer and lysosomal storage diseases.

Prof. Dr. Sandro Sonnino
Dr. Paola Giussani
Prof. Dr. Jin-ichi Inokuchi
Guest Editors

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 submissions that pass pre-check are 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.

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Keywords

  • gangliosides
  • glycosphingolipids
  • sphingomyelin
  • ceramide and ceramide phosphate
  • sphingosine and sphingosine phosphate

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Published Papers (7 papers)

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Research

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15 pages, 4065 KiB  
Article
Correlations between Skin Condition Parameters and Ceramide Profiles in the Stratum Corneum of Healthy Individuals
by Fuminari Akiyama, Natsumi Takahashi, Yuto Ueda, Shizuno Tada, Nobuyuki Takeuchi, Yusuke Ohno and Akio Kihara
Int. J. Mol. Sci. 2024, 25(15), 8291; https://doi.org/10.3390/ijms25158291 - 29 Jul 2024
Viewed by 996
Abstract
Ceramides are essential lipids for skin barrier function, and various classes and species exist in the human stratum corneum (SC). To date, the relationship between skin conditions and ceramide composition in healthy individuals has remained largely unclear. In the present study, we measured [...] Read more.
Ceramides are essential lipids for skin barrier function, and various classes and species exist in the human stratum corneum (SC). To date, the relationship between skin conditions and ceramide composition in healthy individuals has remained largely unclear. In the present study, we measured six skin condition parameters (capacitance, transepidermal water loss, scaliness, roughness, multilayer exfoliation, and corneocyte cell size) for the SC of the cheeks and upper arms of 26 healthy individuals and performed correlation analyses with their SC ceramide profiles, which we measured via liquid chromatography–tandem mass spectrometry. In the cheeks, high levels and/or ratios of two free ceramide classes containing an extra hydroxyl group in the long-chain moiety and a protein-bound ceramide class containing 6-hydroxysphingosine correlated with healthy skin conditions. In contrast, the ratios of two other free ceramide classes, both containing sphingosine, and a protein-bound ceramide class containing 4,14-sphingadiene correlated with unhealthy skin conditions, as did shortening of the carbon chain of the fatty acid portion of two ceramide classes containing non-hydroxy fatty acids. Thus, our findings help to elucidate the relationship between skin conditions and ceramide composition. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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20 pages, 12896 KiB  
Article
Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide
by Rocío Bautista-Pérez, Agustina Cano-Martínez, Manuel Alejandro Herrera-Rodríguez, María del Pilar Ramos-Godinez, Olga Lidia Pérez Reyes, Yolanda Irasema Chirino, Zariá José Rodríguez Serrano and Rebeca López-Marure
Int. J. Mol. Sci. 2024, 25(11), 5881; https://doi.org/10.3390/ijms25115881 - 28 May 2024
Cited by 1 | Viewed by 1083
Abstract
Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) [...] Read more.
Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin–eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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Review

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20 pages, 1927 KiB  
Review
Biological Importance of Complex Sphingolipids and Their Structural Diversity in Budding Yeast Saccharomyces cerevisiae
by Motohiro Tani
Int. J. Mol. Sci. 2024, 25(22), 12422; https://doi.org/10.3390/ijms252212422 - 19 Nov 2024
Viewed by 350
Abstract
Complex sphingolipids are components of eukaryotic biomembranes and are involved in various physiological functions. In addition, their synthetic intermediates and metabolites, such as ceramide, sphingoid long-chain base, and sphingoid long-chain base 1-phosphate, play important roles as signaling molecules that regulate intracellular signal transduction [...] Read more.
Complex sphingolipids are components of eukaryotic biomembranes and are involved in various physiological functions. In addition, their synthetic intermediates and metabolites, such as ceramide, sphingoid long-chain base, and sphingoid long-chain base 1-phosphate, play important roles as signaling molecules that regulate intracellular signal transduction systems. Complex sphingolipids have a large number of structural variations, and this structural diversity is considered an important molecular basis for their various physiological functions. The budding yeast Saccharomyces cerevisiae has simpler structural variations in complex sphingolipids compared to mammals and is, therefore, a useful model organism for elucidating the physiological significance of this structural diversity. In this review, we focus on the structure and function of complex sphingolipids in S. cerevisiae and summarize the response mechanisms of S. cerevisiae to metabolic abnormalities in complex sphingolipids. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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25 pages, 5905 KiB  
Review
Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases
by Fei Fu, Wanmeng Li, Xiaoyin Zheng, Yaling Wu, Dan Du and Chenxia Han
Int. J. Mol. Sci. 2024, 25(21), 11474; https://doi.org/10.3390/ijms252111474 - 25 Oct 2024
Viewed by 631
Abstract
Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis [...] Read more.
Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells. Nevertheless, no review has encapsulated these advancements. Thus, this review compiles information about the involvement of S1P signaling in exocrine pancreatic disorders, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer, as well as prospective treatment strategies to target S1P signaling for these conditions. The insights presented here possess the potential to offer valuable guidance for the implementation of therapies targeting S1P signaling in various pancreatic diseases. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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24 pages, 2351 KiB  
Review
The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism—An Unconventional Ally in Cancer Treatment
by Johnson Ung, Miki Kassai, Su-Fern Tan, Thomas P. Loughran, Jr., David J. Feith and Myles C. Cabot
Int. J. Mol. Sci. 2024, 25(18), 9825; https://doi.org/10.3390/ijms25189825 - 11 Sep 2024
Viewed by 987
Abstract
The tumor-suppressor sphingolipid ceramide is recognized as a key participant in the cytotoxic mechanism of action of many types of chemotherapy drugs, including anthracyclines, Vinca alkaloids, the podophyllotoxin etoposide, taxanes, and the platinum drug oxaliplatin. These drugs can activate de novo synthesis of [...] Read more.
The tumor-suppressor sphingolipid ceramide is recognized as a key participant in the cytotoxic mechanism of action of many types of chemotherapy drugs, including anthracyclines, Vinca alkaloids, the podophyllotoxin etoposide, taxanes, and the platinum drug oxaliplatin. These drugs can activate de novo synthesis of ceramide or stimulate the production of ceramide via sphingomyelinases to limit cancer cell survival. On the contrary, dysfunctional sphingolipid metabolism, a prominent factor in cancer survival and therapy resistance, blunts the anticancer properties of ceramide-orchestrated cell death pathways, especially apoptosis. Although P-glycoprotein (P-gp) is famous for its role in chemotherapy resistance, herein, we propose alternate interpretations and discuss the capacity of this multidrug transporter as a “ceramide neutralizer”, an unwelcome event, highlighting yet another facet of P-gp’s versatility in drug resistance. We introduce sphingolipid metabolism and its dysfunctional regulation in cancer, present a summary of factors that contribute to chemotherapy resistance, explain how P-gp “neutralizes” ceramide by hastening its glycosylation, and consider therapeutic applications of the P-gp-ceramide connection in the treatment of cancer. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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13 pages, 4723 KiB  
Review
Glutamate, Gangliosides, and the Synapse: Electrostatics at Work in the Brain
by Henri Chahinian, Nouara Yahi and Jacques Fantini
Int. J. Mol. Sci. 2024, 25(16), 8583; https://doi.org/10.3390/ijms25168583 - 6 Aug 2024
Cited by 2 | Viewed by 1210
Abstract
The synapse is a piece of information transfer machinery replacing the electrical conduction of nerve impulses at the end of the neuron. Like many biological mechanisms, its functioning is heavily affected by time constraints. The solution selected by evolution is based on chemical [...] Read more.
The synapse is a piece of information transfer machinery replacing the electrical conduction of nerve impulses at the end of the neuron. Like many biological mechanisms, its functioning is heavily affected by time constraints. The solution selected by evolution is based on chemical communication that, in theory, cannot compete with the speed of nerve conduction. Nevertheless, biochemical and biophysical compensation mechanisms mitigate this intrinsic weakness: (i) through the high concentrations of neurotransmitters inside the synaptic vesicles; (ii) through the concentration of neurotransmitter receptors in lipid rafts, which are signaling platforms; indeed, the presence of raft lipids, such as gangliosides and cholesterol, allows a fine tuning of synaptic receptors by these lipids; (iii) through the negative electrical charges of the gangliosides, which generate an attractive (for cationic neurotransmitters, such as serotonin) or repulsive (for anionic neurotransmitters, such as glutamate) electric field. This electric field controls the flow of glutamate in the tripartite synapse involving pre- and post-synaptic neurons and the astrocyte. Changes in the expression of brain gangliosides can disrupt the functioning of the glutamatergic synapse, causing fatal diseases, such as Rett syndrome. In this review, we propose an in-depth analysis of the role of gangliosides in the glutamatergic synapse, highlighting the primordial and generally overlooked role played by the electric field of synaptic gangliosides. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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27 pages, 1396 KiB  
Review
Polar Glycerolipids and Membrane Lipid Rafts
by Anatoly Zhukov and Mikhail Vereshchagin
Int. J. Mol. Sci. 2024, 25(15), 8325; https://doi.org/10.3390/ijms25158325 - 30 Jul 2024
Viewed by 927
Abstract
Current understanding of the structure and functioning of biomembranes is impossible without determining the mechanism of formation of membrane lipid rafts. The formation of liquid-ordered and disordered phases (Lo and Ld) and lipid rafts in membranes and their simplified models is discussed. A [...] Read more.
Current understanding of the structure and functioning of biomembranes is impossible without determining the mechanism of formation of membrane lipid rafts. The formation of liquid-ordered and disordered phases (Lo and Ld) and lipid rafts in membranes and their simplified models is discussed. A new consideration of the processes of formation of lipid phases Lo and Ld and lipid rafts is proposed, taking into account the division of each of the glycerophospholipids into several groups. Generally accepted three-component schemes for modeling the membrane structure are critically considered. A four-component scheme is proposed, which is designed to more accurately assume the composition of lipids in the resulting Lo and Ld phases. The role of the polar head groups of phospholipids and, in particular, phosphatidylethanolamine is considered. The structure of membrane rafts and the possible absence of a clear boundary between the Lo and Ld phases are discussed. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Advances in Sphingolipids)
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