Ceramide Domains in Health and Disease: A Biophysical Perspective

Ventura, Ana E.; Mestre, Beatriz; Silva, Liana C.

doi:10.1007/978-3-030-21162-2_6

Cited by 11 publications

(7 citation statements)

References 290 publications

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“…In addition, alterations in membrane biophysical properties might also influence the internalization, trafficking and sorting of lipids, proteins, drugs and even pathogens. Based on these considerations, the increased content of these lipids in fractions enriched in the apical membrane of HBE-ΔF cells leads to speculate that apical membrane of CF cells is characterized by a more rigid structure that could compromise its function [ 28 , 29 ]. Moreover, the presence of high levels of Cer and glucosylceramide supports the hypothesis that the proinflammatory stimuli are triggered directly from the luminal side of the cell that is exposed to the possible infection and to cells of the immune system that are recruited to the infection site.…”

Section: Resultsmentioning

confidence: 99%

Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis

et al. 2020

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Human primary bronchial epithelial cells differentiated in vitro represent a valuable tool to study lung diseases such as cystic fibrosis (CF), an inherited disorder caused by mutations in the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator. In CF, sphingolipids, a ubiquitous class of bioactive lipids mainly associated with the outer layer of the plasma membrane, seem to play a crucial role in the establishment of the severe lung complications. Nevertheless, no information on the involvement of sphingolipids and their metabolism in the differentiation of primary bronchial epithelial cells are available so far. Here we show that ceramide and globotriaosylceramide increased during cell differentiation, whereas glucosylceramide and gangliosides content decreased. In addition, we found that apical plasma membrane of differentiated bronchial cells is characterized by a higher content of sphingolipids in comparison to the other cell membranes and that activity of sphingolipids catabolic enzymes associated with this membrane results altered with respect to the total cell activities. In particular, the apical membrane of CF cells was characterized by high levels of ceramide and glucosylceramide, known to have proinflammatory activity. On this basis, our data further support the role of sphingolipids in the onset of CF lung pathology.

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Section: Resultsmentioning

confidence: 99%

Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis

et al. 2020

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“…De novo sphingolipid synthesis starts with the condensation of palmitoyl-CoA and serine via the actions of serine palmitoyl-CoA transferase to form 3ketosphinanine [250]. Following the conversion of 3ketosphinanine to sphinganine, a fatty acyl-CoA is attached to the backbone by ceramide synthase to produce dihydroceramide, which can be further modified to form ceramide and into other complex sphingolipids like sphingomyelin, sphingosine-1-phosphate, and glycosphingolipids [251]. In general terms, ceramide and sphingosine-1-phosphate have opposing roles in regulating cancer cell death and survival, and the role that ceramide synthases and sphingosine kinases have been recently reviewed in detail [115].…”

Section: Simple and Complex Lipid Synthesismentioning

confidence: 99%

The diversity and breadth of cancer cell fatty acid metabolism

2021

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Tumor cellular metabolism exhibits distinguishing features that collectively enhance biomass synthesis while maintaining redox balance and cellular homeostasis. These attributes reflect the complex interactions between cell-intrinsic factors such as genomic-transcriptomic regulation and cell-extrinsic influences, including growth factor and nutrient availability. Alongside glucose and amino acid metabolism, fatty acid metabolism supports tumorigenesis and disease progression through a range of processes including membrane biosynthesis, energy storage and production, and generation of signaling intermediates. Here, we highlight the complexity of cellular fatty acid metabolism in cancer, the various inputs and outputs of the intracellular free fatty acid pool, and the numerous ways that these pathways influence disease behavior.

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“…Beyond the membrane reorganizing capacities (78), ceramides also act as second messengers transducing cellular signals (79). These functions widely differ among the diverse cell types, ranging from induction of senescence to apoptosis.…”

Section: Ceramide As Second Messengermentioning

confidence: 99%

Keep Your Friends Close, but Your Enemies Closer: Role of Acid Sphingomyelinase During Infection and Host Response

Chung

Claus

2021

Front. Med.

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Breakdown of the inert and constitutive membrane building block sphingomyelin to the highly active lipid mediator ceramide by extracellularly active acid sphingomyelinase is tightly regulated during stress response and opens the gate for invading pathogens, triggering the immune response, development of remote organ failure, and tissue repair following severe infection. How do one enzyme and one mediator manage all of these affairs? Under physiological conditions, the enzyme is located in the lysosomes and takes part in the noiseless metabolism of sphingolipids, but following stress the protein is secreted into circulation. When secreted, acid sphingomyelinase (ASM) is able to hydrolyze sphingomyelin present at the outer leaflet of membranes to ceramide. Its generation troubles the biophysical context of cellular membranes resulting in functional assembly and reorganization of proteins and receptors, also embedded in highly conserved response mechanisms. As a consequence of cellular signaling, not only induction of cell death but also proliferation, differentiation, and fibrogenesis are affected. Here, we discuss the current state of the art on both the impact and function of the enzyme during host response and damage control. Also, the potential role of lysosomotropic agents as functional inhibitors of this upstream alarming cascade is highlighted.

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Ceramide Domains in Health and Disease: A Biophysical Perspective

Cited by 11 publications

References 290 publications

Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis

Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis

The diversity and breadth of cancer cell fatty acid metabolism

Keep Your Friends Close, but Your Enemies Closer: Role of Acid Sphingomyelinase During Infection and Host Response

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