Changes in membrane biophysical properties induced by sphingomyelinase depend on the sphingolipid N-acyl chain

Pinto, Sandra N.; Laviad, Elad L.; Stiban, Johnny; Kelly, Samuel; Merrill, Alfred H.; Prieto, Manuel; Futerman, Anthony H.; Silva, Liana C.

doi:10.1194/jlr.m042002

Cited by 55 publications

(28 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Long acyl‐chains such as C24‐ceramide can mediate increased hydrophobic interactions and interdigitation in the membrane and thus decrease membrane fluidity when enriched in lipid subdomains. Likewise, shorter acyl‐chains such as C16‐ceramide increase membrane fluidity and disrupt the organization of these domains 33 . Signal transduction events, which rely on clustering and translocation of receptors into these membrane domains, can thus be regulated by the relative amount of chain length‐specific ceramides present in these domains.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, shorter acyl-chains such as C16-ceramide increase membrane fluidity and disrupt the organization of these domains. 33 Signal transduction events, which rely on clustering and translocation of receptors into these membrane domains, can thus be regulated by the relative amount of chain length-specific ceramides present in these domains. The relevance of chain length-specific functions of ceramides to signal transduction pathways induced at the plasma membrane were already shown for the receptors of insulin 34 and TNF-α.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils

et al. 2015

View full text Add to dashboard Cite

Ceramides are mediators of inflammatory processes. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that CerS6 mRNA expression was upregulated 15-fold in peripheral blood leukocytes before the onset of EAE symptoms. In peripheral blood leukocytes from MS patients, a 3.9-fold upregulation was found. Total genetic deletion of CerS6 and the selective deletion of CerS6 in peripheral blood leucocytes exacerbated the progression of clinical symptoms in EAE mice. This was associated with enhanced leukocyte, predominantly neutrophil infiltration and enhanced demyelination in the lumbar spinal cord of EAE mice. Interferon-gamma/tumor necrosis factor alpha (IFN-γ/TNF-α) and granulocyte colony-stimulating factor (G-CSF) both drive EAE development and induce expression of the integrin CD11b and the chemokine receptor C-X-C motif chemokine receptor 2 (CXCR2), and we found they also induce CerS6 expression. In vivo, the genetic deletion of CerS6 enhanced the activation/migration of neutrophils, as reflected by an enhanced upregulation of CD11b and CXCR2. In vitro, the genetic deletion of CerS6 enhanced the activation status of IFN-γ/TNF-α-stimulated neutrophils, as shown by increased expression of nitric oxide and CD11b and an increased adhesion capacity. In G-CSF-stimulated neutrophils, the migration status was enhanced, as reflected by an elevated level of CXCR2 and an increased migration capacity. These data suggest that CerS6/C16-Cer mediates feedback regulation by inhibiting the formation of CD11b and CXCR2, which are induced either by IFN-γ/TNF-α or by G-CSF, respectively. We conclude that CerS6/C16-Cer mediates anti-inflammatory effects during the development of EAE and MS possibly by suppressing the migration and deactivation of neutrophils.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Ceramides have also been proposed to influence membrane fluidity, which has been suggested to play a role in regulating cell migration (7,8). The effects of ceramide on membrane fluidity are complex and depend on acyl chain length (9), saturation (10), and ratio of long chain and very-long chain species present in the membrane (11,12). Furthermore, ceramides may also regulate membrane permeabilization by formation of channels in mitochondrial and lysosomal membranes.…”

Section: Ceramide Membrane Dynamicsmentioning

confidence: 99%

Advances in determining signaling mechanisms of ceramide and role in disease

Stith

Velazquez

Obeid

2019

Journal of Lipid Research

View full text Add to dashboard Cite

Ceramide is a critical bioactive lipid involved in diverse cellular processes. It has been proposed to regulate cellular processes by influencing membrane properties and by directly interacting with effector proteins. Advances over the past decade have improved our understanding of ceramide as a bioactive lipid. Generation and characterization of ceramide-metabolizing enzyme KO mice, development of specific inhibitors and ceramide-specific antibodies, use of advanced microscopy and mass spectrometry, and design of synthetic ceramide derivatives have all provided insight into the signaling mechanisms of ceramide and its implications in disease. As a result, the role of ceramide in biological functions and disease are now better understood, with promise for development of therapeutic strategies to treat ceramide-regulated diseases.

show abstract

“…Recent work on CER have shown that long-chain (C16-C20) and very-long-chain (C22-C24) CER exert reverse effects on cell proliferation and on plasma membrane fluidity (Hartmann et al, 2012;Pinto et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Decreased Serum Levels of Sphingomyelins and Ceramides in Sickle Cell Disease Patients

Aslan

Kıraç

Kaya

et al. 2018

Lipids

View full text Add to dashboard Cite

Limited data are available on the serum levels of different sphingomyelin (CerPCho) and ceramide (CER) species in sickle-cell disease (SCD). This study was aimed at identifying the levels of C16-C24 CerPCho and C16-C24 CER in serum obtained from SCD patients and controls. Circulating levels of neutral sphingomyelinase (N-SMase) activity, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P) were also determined. Blood was collected from 35 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients. Serum levels of C16-C24 CerPCho and C16-C24 CER were determined by an optimized multiple reaction monitoring (MRM) method using ultrafast liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of N-SMase was assayed by standard kit methods, and C1P and S1P levels were determined by enzyme-linked immunosorbent assay. A significant decrease was observed in the serum levels of C18-C24 CerPCho in patients with SCD compared to controls. No significant difference was found in C16 CerPCho levels between the two groups. Very-long-chain C22-C24 CER were significantly decreased in SCD, while long-chain C16-C20 CER levels showed no significant difference between SCD patients and controls. Significant positive correlation was found between the serum total cholesterol levels and C18-C24 CerPCho and C22-C24 CER in SCD patients. Patients with SCD had significantly elevated serum activity of N-SMase as well as increased circulating levels of C1P and S1P compared to controls. The decrease in serum levels of C18-C24 CerPCho in patients with SCD was accompanied by decreased levels of C22-C24 CER. Future studies are needed to understand the role of decreased CerPCho and CER in the pathophysiology of SCD.

show abstract

Changes in membrane biophysical properties induced by sphingomyelinase depend on the sphingolipid N-acyl chain

Cited by 55 publications

References 51 publications

Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils

Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils

Advances in determining signaling mechanisms of ceramide and role in disease

Decreased Serum Levels of Sphingomyelins and Ceramides in Sickle Cell Disease Patients

Contact Info

Product

Resources

About