Dihydroceramide hinders ceramide channel formation: Implications on apoptosis

Stiban, Johnny; Fistere, D.; Colombini, Marco

doi:10.1007/s10495-006-5882-8

Cited by 125 publications

(88 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In another study, inhibition of dhCer synthesis correlated with reduced viability in T-cell leukemia line [94]. Ceramide-to-dhCer ratio was shown to be a determinant in the apoptotic decision in another report, possibly by modulating ceramide channels through conversion of ceramide to dhCer [95]. Loss of dhCer was correlated with rapid cell growth and increased apoptosis interestingly, and this phenotype was rescued with the activation of dhCer synthesis in some neurodegerative disorders [96].…”

Section: Dihydrosphingosinementioning

confidence: 88%

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Ekiz

Baran²

2011

ACAMC

View full text Add to dashboard Cite

Sphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias.

show abstract

Section: Dihydrosphingosinementioning

confidence: 88%

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Ekiz

Baran²

2011

ACAMC

View full text Add to dashboard Cite

show abstract

“…Additionally, these fatty acid chain lengths within the ceramide have the ability to alter its bioactivity [58]. Specifically, it has been shown that intracellular C16-ceramide is particularly pro-apoptotic, whereas C24-ceramide and dihydroceramides antagonize apoptosis induced by shorter ceramides [59][60][61]. Interestingly, both C16-ceramide and C24-ceramide treatment of macrophages resulted in a significant reduction in TNF-α and CCL2 mRNA expression, while dihydroceramides had no effect.…”

Section: Discussionmentioning

confidence: 99%

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

et al. 2017

View full text Add to dashboard Cite

High-fat diets (HFD) increase lipopolysaccharide (LPS) activity in the blood and may contribute to systemic inflammation with obesity. We hypothesized that dietary milk sphingomyelin (SM), which reduces lipid absorption and colitis in mice, would reduce inflammation and be mediated through effects on gut health and LPS activity. C57BL/6J mice were fed high-fat, high-cholesterol diets (HFD, n = 14) or the same diets with milk SM (HFD-MSM, 0.1% by weight, n = 14) for 10 weeks. HFD-MSM significantly reduced serum inflammatory markers and tended to lower serum LPS (p = 0.08) compared to HFD. Gene expression related to gut barrier function and macrophage inflammation were largely unchanged in colon and mesenteric adipose tissues. Cecal gut microbiota composition showed greater abundance of Acetatifactor genus in mice fed milk SM, but minimal changes in other taxa. Milk SM significantly attenuated the effect of LPS on pro-inflammatory gene expression in RAW264.7 macrophages. Milk SM lost its effects when hydrolysis was blocked, while long-chain ceramides and sphingosine, but not dihydroceramides, were anti-inflammatory. Our data suggest that dietary milk SM may be effective in reducing systemic inflammation through inhibition of LPS activity and that hydrolytic products of milk SM are important for these effects.

show abstract

“…Cette double liaison semble associée à des propriétés régulatrices du céramide, que ne possède pas son précurseur le dihydrocéramide, notamment sur l'apoptose [39]. En effet, le céramide peut former des canaux dans la membrane externe de la mitochondrie, permettant le relargage de petites protéines (notamment le cytochrome c) [42]. La myristoylation des deux isoformes de la dihydrocéramide Δ4-désaturase (DES1 et DES2) a été démontrée chez le rat.…”

Section: Acide Myristique Et Régulation De La Biodisponibilité Des Acunclassified

Acide myristique : nouvelles fonctions de régulation et de signalisation

2009

View full text Add to dashboard Cite

Parmi les acides gras saturés les plus consommés dans l'alimentation humaine, l'acide myristique (acide saturé linéaire à 14 carbones, CH 3 -[CH 2 ] 12 -COOH, C14:0) arrive en troisième position, loin derrière l'acide palmitique (CH 3 -[CH 2 ] 14 -COOH, C16:0) et l'acide stéa-rique (CH 3 -[CH 2 ] 16 -COOH, C18:0) [1]. Présent en quantité importante dans la matière grasse laitière (il représente environ 10 % des acides gras), l'acide myristique occupe majoritairement la position sn-2 1 [2] sur les triglycérides, ce qui lui assure une absorption intestinale efficace sous forme de 2-monoglycéride. Dans la cellule animale, l'acide myristique est relativement rare et représente en moyenne 1 % des acides gras. Sa biosynthèse endogène faible (quelques centaines de μg dans le foie) rend son origine alimentaire quantitativement prépondérante (entre 4 et 8 g/jour) [3]. Lorsqu'il est ajouté à des hépatocytes en culture, l'acide myristique est majoritairement incorporé dans les lipides cellulaires (65 % du C14:0 initial) mais est aussi largement β-oxydé (30 %) (Figure 1) [4].La description des rôles physiologiques de l'acide myristique a longtemps été restreinte à sa responsabilité dans la hausse du cholestérol plasmatique chez l'homme et l'animal, quand il est apporté en excès dans 1 Sn dénote les atomes de carbone. l'alimentation [5], ce qui explique sa mauvaise répu-tation nutritionnelle. Ces résultats, bien que remis en cause depuis que les études nutritionnelles explorent l'impact des doses raisonnables d'acides gras saturés totaux et d'acide myristique en particulier [6,7], ont largement contribué à masquer les autres fonctions biologiques importantes de cet acide gras ainsi que les bases moléculaires de ces fonctions.

show abstract

Dihydroceramide hinders ceramide channel formation: Implications on apoptosis

Cited by 125 publications

References 44 publications

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

Acide myristique : nouvelles fonctions de régulation et de signalisation

Contact Info

Product

Resources

About