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Ceramide in cystic fibrosis: a potential new target for therapeutic intervention.

Wojewodka G, De Sanctis JB, Radzioch D - J Lipids (2010)

Bottom Line: These characteristics of ceramides make them strong candidates for therapeutic intervention in CF.As more studies have come to evaluate the role of ceramide in CF, conflicting results have been described.This paper discusses various views regarding the potential role of ceramide in CF, summarizes methods of ceramide detection and their role in the regulation of cellular and molecular processes.

View Article: PubMed Central - PubMed

Affiliation: Human Genetics, McGill University Health Center Research Institute, 1650 Cedar Avenue L11-218, Montreal, QC, Canada H3G 1A4.

ABSTRACT
Patients with cystic fibrosis (CF) are afflicted with many symptoms but the greatest challenge is the fight against chronic bacterial infections, leading to decreased lung function and ultimately death. Our group has recently found reduced levels of ceramides in CF patients and mice. Ceramides are sphingolipids involved in the structure of cell membranes but also participate in the inflammatory response, in cell signalling through membrane microdomains (lipid rafts), and in apoptosis. These characteristics of ceramides make them strong candidates for therapeutic intervention in CF. As more studies have come to evaluate the role of ceramide in CF, conflicting results have been described. This paper discusses various views regarding the potential role of ceramide in CF, summarizes methods of ceramide detection and their role in the regulation of cellular and molecular processes.

No MeSH data available.


Related in: MedlinePlus

Synthesis pathway of ceramide. There exist two pathways for ceramide synthesis: de  novo pathway and recycling pathway. The de novo pathway occurs in the endoplasmic reticulum while the recycling pathway occurs in vesicular and cell membranes.
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fig1: Synthesis pathway of ceramide. There exist two pathways for ceramide synthesis: de novo pathway and recycling pathway. The de novo pathway occurs in the endoplasmic reticulum while the recycling pathway occurs in vesicular and cell membranes.

Mentions: There are two pathways for ceramide synthesis (Figure 1). The de novo pathway occurs in the endoplasmic reticulum and begins with the conversion of serine and palmitoyl-CoA to sphinganine by serine palmitoyl transferase. Ceramide synthases then transform sphinganine into dihydroceramide which is converted to ceramide by dihydroceramide desaturase. Alternatively, ceramide can be synthesized through a recycling pathway with the conversion of sphingomyelin to ceramide by sphingomyelinase (SMase) [9]. There are several types of SMase categorized based on pH optima and localization in the cell: acidic (aSMase), neutral (nSMase), and alkaline (Alk-SMase) [11]. Generally a pH of 4.5–5.0 is optimal for aSMase and it is localized mainly in lysosomal compartments in the cells as well as in membrane microdomains (discussed later) in the cell membrane [12]. Neutral SMases have a pH optima of 7.4 [12] and can be located in the plasma membrane [13]. Alk-SMase is mainly found to be expressed in the intestines [14]. Considering that the deficiency in ceramides in CF can be corrected by fenretinide and the induction of dihydroceramide, the precursor to ceramide, can be detected [8], these findings suggest that the de novo pathway involving the endoplasmic reticulum is targeted by this drug in CF as it was described before in the context of cancer.


Ceramide in cystic fibrosis: a potential new target for therapeutic intervention.

Wojewodka G, De Sanctis JB, Radzioch D - J Lipids (2010)

Synthesis pathway of ceramide. There exist two pathways for ceramide synthesis: de  novo pathway and recycling pathway. The de novo pathway occurs in the endoplasmic reticulum while the recycling pathway occurs in vesicular and cell membranes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066841&req=5

fig1: Synthesis pathway of ceramide. There exist two pathways for ceramide synthesis: de novo pathway and recycling pathway. The de novo pathway occurs in the endoplasmic reticulum while the recycling pathway occurs in vesicular and cell membranes.
Mentions: There are two pathways for ceramide synthesis (Figure 1). The de novo pathway occurs in the endoplasmic reticulum and begins with the conversion of serine and palmitoyl-CoA to sphinganine by serine palmitoyl transferase. Ceramide synthases then transform sphinganine into dihydroceramide which is converted to ceramide by dihydroceramide desaturase. Alternatively, ceramide can be synthesized through a recycling pathway with the conversion of sphingomyelin to ceramide by sphingomyelinase (SMase) [9]. There are several types of SMase categorized based on pH optima and localization in the cell: acidic (aSMase), neutral (nSMase), and alkaline (Alk-SMase) [11]. Generally a pH of 4.5–5.0 is optimal for aSMase and it is localized mainly in lysosomal compartments in the cells as well as in membrane microdomains (discussed later) in the cell membrane [12]. Neutral SMases have a pH optima of 7.4 [12] and can be located in the plasma membrane [13]. Alk-SMase is mainly found to be expressed in the intestines [14]. Considering that the deficiency in ceramides in CF can be corrected by fenretinide and the induction of dihydroceramide, the precursor to ceramide, can be detected [8], these findings suggest that the de novo pathway involving the endoplasmic reticulum is targeted by this drug in CF as it was described before in the context of cancer.

Bottom Line: These characteristics of ceramides make them strong candidates for therapeutic intervention in CF.As more studies have come to evaluate the role of ceramide in CF, conflicting results have been described.This paper discusses various views regarding the potential role of ceramide in CF, summarizes methods of ceramide detection and their role in the regulation of cellular and molecular processes.

View Article: PubMed Central - PubMed

Affiliation: Human Genetics, McGill University Health Center Research Institute, 1650 Cedar Avenue L11-218, Montreal, QC, Canada H3G 1A4.

ABSTRACT
Patients with cystic fibrosis (CF) are afflicted with many symptoms but the greatest challenge is the fight against chronic bacterial infections, leading to decreased lung function and ultimately death. Our group has recently found reduced levels of ceramides in CF patients and mice. Ceramides are sphingolipids involved in the structure of cell membranes but also participate in the inflammatory response, in cell signalling through membrane microdomains (lipid rafts), and in apoptosis. These characteristics of ceramides make them strong candidates for therapeutic intervention in CF. As more studies have come to evaluate the role of ceramide in CF, conflicting results have been described. This paper discusses various views regarding the potential role of ceramide in CF, summarizes methods of ceramide detection and their role in the regulation of cellular and molecular processes.

No MeSH data available.


Related in: MedlinePlus