Ceramide and ceramide 1-phosphate in health and disease

Arana, Lide; Gangoiti, Patricia; Ouro, Alberto; Trueba, Miguel; Gómez-Muñoz, Antonio

doi:10.1186/1476-511x-9-15

Cited by 178 publications

(136 citation statements)

References 162 publications

(181 reference statements)

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…It is remarkable that while the role of S1P and S1P receptor-agonists/antagonists in the pathogenesis of inflammatory disorders has been extensively studied in vivo using translational mouse models of human diseases [9,10,25], the knowledge concerning the function of exogenous C1P in modulating immune responses is, at present, mostly limited to in vitro observations [26,27]. Both pro-and anti-inflammatory behaviour of exogenous C1P has been described.…”

Section: Discussionmentioning

confidence: 99%

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation

et al. 2015

Self Cite

View full text Add to dashboard Cite

Sphingolipids are involved in the pathogenesis of inflammatory diseases. The central molecule is ceramide, which can be converted into ceramide-1-phosphate (C1P). Although C1P can exert anti-and pro-inflammatory effects, its influence on cigarette smoke (CS)-induced lung inflammation is unknown. We aimed to clarify the role of C1P in the pathogenesis of CS-triggered pulmonary inflammation and emphysema in humans and mice.The effects of C1P were addressed on CS-induced lung inflammation in C57BL/6 mice, CS extracttriggered activation of human airway epithelial cells (AECs) and neutrophils from patients with chronic obstructive pulmonary disease. Differential cell counts in bronchoalveolar lavage fluid were determined by flow cytometry and pro-inflammatory cytokines were measured by ELISA. Expression and DNA binding of nuclear factor (NF)-κB and neutral sphingomyelinase (nSMase) were quantified by PCR, electrophoretic mobility shift and fluorometric assays.C1P reduced CS-induced acute and chronic lung inflammation and development of emphysema in mice, which was associated with a reduction in nSMase and NF-κB activity in the lungs. nSMase activity in human serum correlated negatively with forced expiratory volume in 1 s % predicted. In human AECs and neutrophils, C1P inhibited CS-induced activation of NF-κB and nSMase, and reduced pro-inflammatory cytokine release.Our results suggest that C1P is a potential target for anti-inflammatory treatment in CS-induced lung inflammation. @ERSpublications Ceramide-1-phosphate, a potential target for anti-inflammatory treatment in cigarette smokeinduced lung inflammation

show abstract

Section: Discussionmentioning

confidence: 99%

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, DES1 may significantly impact ceramide signaling processes because the enzyme essentially modulates the dihydroceramide/ceramide ratio in cells (52). As ceramide mediates apoptosis (53), senescence (54), cell growth regulation (55), signaling processes (56), and other diverse functions in cells (57), it may serve as a therapeutic target for a variety of illnesses. Especially promising in this regard is that DES1 null mice demonstrated no susceptibility to insulin resistance caused by nutrient excess or glucocorticoid therapy (58).…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Dihydroceramide Desaturase by Palmitate versus Monounsaturated Fatty Acids

Ross

Geng

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Much data implicate saturated fatty acids in deleterious processes associated with obesity, diabetes, and the metabolic syndrome. Many of these changes may be due to aberrant generation of bioactive lipids when saturated fatty acid availability to tissues is increased. On the other hand, studies are emerging that implicate the monounsaturated fatty acid oleate in protection from saturated fat mediated toxicity; however, the mechanisms are not well understood. Our data demonstrate a novel role for palmitate in increasing mRNA encoding DES1, which is the enzyme responsible for generating ceramide from its precursor dihydroceramide and thus controls synthesis of the bioactive lipid ceramide. Moreover, co-treatment with oleate prevented the increase in ceramide, and this occurred through attenuation of the increase in message and activity of DES1. Knockdown of DES1 also protected from palmitate-induced insulin resistance, and overexpression of this enzyme ameliorated the protective effect of oleate. Together, these findings provide insight into the mechanisms of oleate-mediated protection against metabolic disease and provide novel evidence for fatty acid-mediated regulation of a key enzyme of ceramide biosynthesis.The rise in obesity in recent years has initiated a pandemic of metabolic disease including heart disease and diabetes (1, 2). Perturbations in lipid metabolism and/or endocrine function that occur in obesity likely mediate the development of a disorders, including insulin resistance, nonalcoholic fatty liver disease, pancreatic cell death, hypertension, and the "metabolic syndrome" (3, 4). Although the mechanistic links between obesity and these pathophysiological processes remain incompletely understood, one proposed mechanism is that the elevation in plasma lipids associated with obesity overloads tissues with precursors for synthesis of bioactive lipids, including diacylglycerols (DAG) 2 and ceramides (5, 6).Epidemiological data link diets high in saturated fatty acids with increased incidence of metabolic disease (6, 7). Supporting a mechanistic connection between saturated fatty acids and metabolic syndrome, many studies demonstrate that the saturated fatty acid palmitate promotes insulin resistance in heart, adipose, and skeletal muscle (8 -10). On the other hand, data are emerging which support that unsaturated fatty acids such as oleate have protective effects against palmitate toxicity, though the mechanisms are not fully understood (11,12).Several studies demonstrate that ceramide plays a key role in insulin resistance in human skeletal muscle cells (13-15). Biosynthesis of sphingolipids including ceramide begins with condensation of serine with acyl-CoA such as palmitoyl-CoA. Exposing muscle cells to palmitate increased ceramide synthesis and inhibited insulin stimulation of Akt/protein kinase B, a serine/threonine kinase that is a central mediator of insulinstimulated anabolic metabolism (13); moreover, inhibiting ceramide synthesis negated the antagonistic effect of saturated free fatty acid...

show abstract

“…Ceramide kinase is an enzyme that converts ceramide (Cer) into ceramide 1-phosphate (Cer-1p), a molecule that has a clear signaling function in animal cells (Arana et al, 2010). In Arabidopsis plants that have a mutation in ACCELERATED CELL DEATH5 (ACD5), whose product has ceramide kinase activity, plants initially develop normally.…”

Section: Introductionmentioning

confidence: 99%

Loss of Ceramide Kinase in Arabidopsis Impairs Defenses and Promotes Ceramide Accumulation and Mitochondrial H₂O₂ Bursts

Liu

et al. 2014

Plant Cell

146

View full text Add to dashboard Cite

Arabidopsis thaliana plants that lack ceramide kinase, encoded by ACCELERATED CELL DEATH5 (ACD5), display spontaneous programmed cell death late in development and accumulate substrates of ACD5. Here, we compared ceramide accumulation kinetics, defense responses, ultrastructural features, and sites of reactive oxygen species (ROS) production in wild-type and acd5 plants during development and/or Botrytis cinerea infection. Quantitative sphingolipid profiling indicated that ceramide accumulation in acd5 paralleled the appearance of spontaneous cell death, and it was accompanied by autophagy and mitochondrial ROS accumulation. Plants lacking ACD5 differed significantly from the wild type in their responses to B. cinerea, showing earlier and higher increases in ceramides, greater disease, smaller cell wall appositions (papillae), reduced callose deposition and apoplastic ROS, and increased mitochondrial ROS. Together, these data show that ceramide kinase greatly affects sphingolipid metabolism and the site of ROS accumulation during development and infection, which likely explains the developmental and infection-related cell death phenotypes. The acd5 plants also showed an early defect in restricting B. cinerea germination and growth, which occurred prior to the onset of cell death. This early defect in B. cinerea restriction in acd5 points to a role for ceramide phosphate and/or the balance of ceramides in mediating early antifungal responses that are independent of cell death.

show abstract

Ceramide and ceramide 1-phosphate in health and disease

Cited by 178 publications

References 162 publications

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation

Differential Regulation of Dihydroceramide Desaturase by Palmitate versus Monounsaturated Fatty Acids

Loss of Ceramide Kinase in Arabidopsis Impairs Defenses and Promotes Ceramide Accumulation and Mitochondrial H₂O₂ Bursts

Contact Info

Product

Resources

About

Ceramide and ceramide 1-phosphate in health and disease

Cited by 178 publications

References 162 publications

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation

Differential Regulation of Dihydroceramide Desaturase by Palmitate versus Monounsaturated Fatty Acids

Loss of Ceramide Kinase in Arabidopsis Impairs Defenses and Promotes Ceramide Accumulation and Mitochondrial H2O2 Bursts

Contact Info

Product

Resources

About

Loss of Ceramide Kinase in Arabidopsis Impairs Defenses and Promotes Ceramide Accumulation and Mitochondrial H₂O₂ Bursts