Ceramide: A simple sphingolipid with unique biophysical properties

Castro, Bruno M.; Prieto, Manuel; Silva, Liana C.

doi:10.1016/j.plipres.2014.01.004

Cited by 314 publications

(258 citation statements)

References 162 publications

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“…Although the mechanisms by which ceramide regulates BSX expression are unclear, two sets of observations are relevant: i) ceramide forms gel-phase platforms in the plasma membrane and recruits target proteins for specific signaling that can regulate gene expression [53,54]; and ii) ceramides or their soluble derivatives, such as ceramide-1-phosphate and sphingosine, bind transcription factors and modulate target gene expression [55][56][57][58].…”

Section: Control Of Appetite and Body Weightmentioning

confidence: 99%

Carnitine palmitoyltransferase 1C: From cognition to cancer

Casals

Zammit

Herrero

et al. 2016

Progress in Lipid Research

110

101

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Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression.Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with L-carnitine and acyl-CoA esters. The lack of an easily measurable biological activity has hampered attempts to elucidate the cellular and physiological role of CPT1C but has not diminished the interest of the biomedical research community in this CPT1 isoform. The observations that CPT1C binds malonyl-CoA and long-chain acyl-CoA suggest that it is a sensor of lipid metabolism in neurons, where it appears to impact ceramide and triacylglycerol (TAG) metabolism.CPT1C global knock-out mice show a wide range of brain disorders, including impaired cognition and spatial learning, motor deficits, and a deregulation in food intake and energy homeostasis. The first disease-causing CPT1C mutation was recently described in humans, with Cpt1c being identified as the gene causing hereditary spastic paraplegia. The putative role of CPT1C in the regulation of complex-lipid metabolism is supported by the observation that it is highly expressed in certain virulent tumor cells, conferring them resistance to glucose-and oxygen-deprivation. Therefore, CPT1C may be a promising target in the treatment of cancer. Here we review the molecular, biochemical, and structural properties of CPT1C and discuss its potential roles in brain function, and cancer.

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Section: Control Of Appetite and Body Weightmentioning

confidence: 99%

Carnitine palmitoyltransferase 1C: From cognition to cancer

Casals

Zammit

Herrero

et al. 2016

Progress in Lipid Research

110

101

View full text Add to dashboard Cite

show abstract

“…One product of sphingomyelin hydrolysis by ASM is the lipid ceramide, an important signaling molecule that is elevated in many common diseases (e.g., diabetes, fibrosis, sepsis, etc) [45][46][47]. ASM is a major source of ceramide, both in lysosomes and at the cell membrane.…”

Section: Disease Mechanismmentioning

confidence: 99%

Types A and B Niemann-Pick disease

Schuchman¹,

Wasserstein²

2015

Best Practice & Research Clinical Endocrinology & Metab

120

136

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“…Functionally, small rafts coalesce together into domains ranging from 70 nm to 1 µm in diameter, depending on the stimulus and the cell type (Gupta and DeFranco, 2003) through additional specific lipid-lipid or lipid-protein interactions that also modulate their thickness (Castro et al, 2014;Lingwood and Simons, 2010;Silva et al, 2007). In addition, the lipid raft coalescence can be regulated by local accumulation of ceramide generated through the hydrolysis of a major constituent of the microdomains, sphingomyelin, by the acid sphingomyelinase enzyme (ASMase, also known as SMPD1) (Castro et al, 2014). Of note, owing to their rapid trans-bilayer movement (flip-flop), ceramide molecules are distributed between the outer and inner leaflets of the surface membrane.…”

Section: Introductionmentioning

confidence: 99%

Keratin impact on PKCδ- and ASMase-mediated regulation of hepatocyte lipid raft size – implication for FasR-associated apoptosis

Gilbert

Loranger

Omary

et al. 2016

Journal of Cell Science

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Keratins are epithelial cell intermediate filament (IF) proteins that are expressed as pairs in a cell-differentiation-regulated manner. Hepatocytes express the keratin 8 and 18 pair (denoted K8/K18) of IFs, and a loss of K8 or K18, as in K8-null mice, leads to degradation of the keratin partner. We have previously reported that a K8/K18 loss in hepatocytes leads to altered cell surface lipid raft distribution and more efficient Fas receptor (FasR, also known as TNFRSF6)-mediated apoptosis. We demonstrate here that the absence of K8 or transgenic expression of the K8 G62C mutant in mouse hepatocytes reduces lipid raft size. Mechanistically, we find that the lipid raft size is dependent on acid sphingomyelinase (ASMase, also known as SMPD1) enzyme activity, which is reduced in absence of K8/K18. Notably, the reduction of ASMase activity appears to be caused by a less efficient redistribution of surface membrane PKCδ toward lysosomes. Moreover, we delineate the lipid raft volume range that is required for an optimal FasR-mediated apoptosis. Hence, K8/ K18-dependent PKCδ-and ASMase-mediated modulation of lipid raft size can explain the more prominent FasR-mediated signaling resulting from K8/K18 loss. The fine-tuning of ASMase-mediated regulation of lipid rafts might provide a therapeutic target for deathreceptor-related liver diseases.

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Ceramide: A simple sphingolipid with unique biophysical properties

Cited by 314 publications

References 162 publications

Carnitine palmitoyltransferase 1C: From cognition to cancer

Carnitine palmitoyltransferase 1C: From cognition to cancer

Types A and B Niemann-Pick disease

Keratin impact on PKCδ- and ASMase-mediated regulation of hepatocyte lipid raft size – implication for FasR-associated apoptosis

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