International Journal of Molecular Sciences

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Dear Colleagues,

The emergence of ceramide as an important mediator in a variety of cellular processes and diseases has stimulated extensive and all-encompassing research. Ceramides are involved in a variety of cellular processes. Their biological functions are thought to depend on ceramides' unique biophysical characteristics, which promote significant alterations of cell membrane properties and consequent triggering of signaling events. Furthermore, an emerging picture suggests that the coupling of ceramide to specific signaling cascades is both stimulus and cell-type specific, and depends on the subcellular topology of its production. Unfortunately, the link between the physical studies reviewed here and the mass of biological and clinical studies on the effects of ceramides in health and disease is tenuous. This Special Issue will discuss the recent advances in the field of ceramide properties in biological processes, thereby contributing to our knowledge on how the biophysical properties of ceramide come into play in both physiological and pathological conditions

Dr. Jean-Pierre Jaffrézou
Guest Editor

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Keywords

ceramide-gel domains
lipid rafts
membrane lipid domains
morphological alterations
N-acyl chain ceramides
Ceramide gel domains
Interdigitation
lipid domain morphology
membrane order
membrane permeability
membrane fusion
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Published Papers (2 papers)

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Research

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15 pages, 2296 KiB

Open AccessArticle

Ceramide Metabolism Regulated by Sphingomyelin Synthase 2 Is Associated with Acquisition of Chemoresistance via Exosomes in Human Leukemia Cells

by Makoto Taniguchi, Shingo Nagaya, Kohei Yuyama, Ai Kotani, Yasuyuki Igarashi and Toshiro Okazaki

Int. J. Mol. Sci. 2022, 23(18), 10648; https://doi.org/10.3390/ijms231810648 - 13 Sep 2022

Cited by 6 | Viewed by 1740

Abstract

Ceramide levels controlled by the sphingomyelin (SM) cycle have essential roles in cancer cell fate through the regulation of cell proliferation, death, metastasis, and drug resistance. Recent studies suggest that exosomes confer cancer malignancy. However, the relationship between ceramide metabolism and exosome-mediated cancer malignancy is unclear. In this study, we elucidated the role of ceramide metabolism via the SM cycle in exosomes and drug resistance in human leukemia HL-60 and adriamycin-resistant HL-60/ADR cells. HL-60/ADR cells showed significantly increased exosome production and release compared with parental chemosensitive HL-60 cells. In HL-60/ADR cells, increased SM synthase (SMS) activity reduced ceramide levels, although released exosomes exhibited a high ceramide ratio in both HL-60- and HL-60/ADR-derived exosomes. Overexpression of SMS2 but not SMS1 suppressed intracellular ceramide levels and accelerated exosome production and release in HL-60 cells. Notably, HL-60/ADR exosomes conferred cell proliferation and doxorubicin resistance properties to HL-60 cells. Finally, microRNA analysis in HL-60 and HL-60/ADR cells and exosomes showed that miR-484 elevation in HL-60/ADR cells and exosomes was associated with exosome-mediated cell proliferation. This suggests that intracellular ceramide metabolism by SMS2 regulates exosome production and release, leading to acquisition of drug resistance and enhanced cell proliferation in leukemia cells. Full article

(This article belongs to the Special Issue Advances in Ceramide Properties in Biological Processes)

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Review

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18 pages, 2264 KiB

Open AccessReview

Involvement of Ceramide Signalling in Radiation-Induced Tumour Vascular Effects and Vascular-Targeted Therapy

by Deepa Sharma and Gregory J. Czarnota

Int. J. Mol. Sci. 2022, 23(12), 6671; https://doi.org/10.3390/ijms23126671 - 15 Jun 2022

Cited by 11 | Viewed by 1859

Abstract

Sphingolipids are well-recognized critical components in several biological processes. Ceramides constitute a class of sphingolipid metabolites that are involved in important signal transduction pathways that play key roles in determining the fate of cells to survive or die. Ceramide accumulated in cells causes apoptosis; however, ceramide metabolized to sphingosine promotes cell survival and angiogenesis. Studies suggest that vascular-targeted therapies increase endothelial cell ceramide resulting in apoptosis that leads to tumour cure. Specifically, ultrasound-stimulated microbubbles (USMB) used as vascular disrupting agents can perturb endothelial cells, eliciting acid sphingomyelinase (ASMase) activation accompanied by ceramide release. This phenomenon results in endothelial cell death and vascular collapse and is synergistic with other antitumour treatments such as radiation. In contrast, blocking the generation of ceramide using multiple approaches, including the conversion of ceramide to sphingosine-1-phosphate (S1P), abrogates this process. The ceramide-based cell survival “rheostat” between these opposing signalling metabolites is essential in the mechanotransductive vascular targeting following USMB treatment. In this review, we aim to summarize the past and latest findings on ceramide-based vascular-targeted strategies, including novel mechanotransductive methodologies. Full article

(This article belongs to the Special Issue Advances in Ceramide Properties in Biological Processes)

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