Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate

Mao, Cungui; Obeid, Lina M.

doi:10.1016/j.bbalip.2008.06.002

Cited by 354 publications

(347 citation statements)

References 140 publications

Supporting

Mentioning

328

Contrasting

Unclassified

Order By: Relevance

“…2). These reactions take place within the plasma membrane (which can generate signaling sphingolipids) as well as in the lysosome, which is an important site of sphingolipid catabolism (Mao and Obeid 2008;Jenkins et al 2009;Schulze and Sandhoff 2011). Lysosomal ceramides and LCBs generated from breakdown of mature sphingolipids exit this organelle by poorly characterized means and return to the secretory pathway, where they can be recycled to form new sphingolipids.…”

Section: Sphingolipid Turnover and Degradationmentioning

confidence: 99%

“…Notable progress has been made in characterizing several sphingolipid catabolic enzymes (for a review, see Mao and Obeid 2008;Jenkins et al 2009). However, these studies have primarily focused on the roles of these enzymes in acute signaling responses rather than on their regulation in the context of sphingolipid homeostasis.…”

Section: Regulation Of Sphingolipid Transport and Turnovermentioning

confidence: 99%

See 1 more Smart Citation

Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond

Breslow

2013

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

Sphingolipids are a diverse group of lipids that have essential cellular roles as structural components of membranes and as potent signaling molecules. In recent years, a detailed picture has emerged of the basic biochemistry of sphingolipids-from their initial synthesis in the endoplasmic reticulum (ER), to their elaboration into complex glycosphingolipids, to their turnover and degradation. However, our understanding of how sphingolipid metabolism is regulated in response to metabolic demand and physiologic cues remains incomplete. Here I discuss new insights into the mechanisms that ensure sphingolipid homeostasis, with an emphasis on the ER as a critical regulatory site in sphingolipid metabolism. In particular, Orm family proteins have recently emerged as key ER-localized mediators of sphingolipid homeostasis. A detailed understanding of how cells sense and control sphingolipid production promises to provide key insights into membrane function in health and disease.

show abstract

Section: Sphingolipid Turnover and Degradationmentioning

confidence: 99%

Section: Regulation Of Sphingolipid Transport and Turnovermentioning

confidence: 99%

Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond

Breslow

2013

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

show abstract

“…According to their pH optima of activity, acid, neutral, and alkaline ceramidases can be distinguished (14). Among these ceramidases, acid ceramidase (aCDase), encoded by the ASAH1 gene, appears to play an important role in cancer progression.…”

mentioning

confidence: 99%

Acid Ceramidase Expression Modulates the Sensitivity of A375 Melanoma Cells to Dacarbazine

Bedia

Casas²,

Andrieu‐Abadie

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Dacarbazine (DTIC) is the treatment of choice for metastatic melanoma, but its response in patients remains very poor. Ceramide has been shown to be a death effector and to play an important role in regulating cancer cell growth upon chemotherapy. Among ceramidases, the enzymes that catabolize ceramide, acid ceramidase (aCDase) has been implicated in cancer progression. Here we show that DTIC elicits a time-and dosedependent decrease of aCDase activity and an increase of intracellular ceramide levels in human A375 melanoma cells. The loss of enzyme activity occurred as a consequence of reactive oxygen species-dependent activation of cathepsin B-mediated degradation of aCDase. These events preceded autophagic features and loss of cell viability. Down-regulation of acid but not neutral or alkaline ceramidase 2 resulted in elevated levels of ceramide and sensitization to the toxic effects of DTIC. Conversely, inducible overexpression of acid but not neutral ceramidase reduced ceramide levels and conferred resistance to DTIC. In conclusion, we report that increased levels of ceramide, due to enhanced degradation of aCDase, are in part responsible for the cell death effects of DTIC. These results suggest that downregulation of aCDase alone or in combination with DTIC may represent a useful tool in the treatment of metastatic melanoma.

show abstract

“…Ceramide, sphingosine and sphingosine-1-phosphate are bioactive lipids that mediate cell proliferation, differentiation, apoptosis, adhesion and migration. 145 Ceramide is further hydrolyzed to free fatty acid and sphingosine, the latter undergoing conversion to sphingosine phosphate by the action of a specific nuclear kinase. 146 Both ceramide and ceramide kinase (CERK) have a role in various signal transduction pathways involved in inflammation.…”

Section: Potential Role For Ceramidementioning

confidence: 99%

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

2009

View full text Add to dashboard Cite

Gaucher disease (GD) is caused by the reduced activity of a lysosomal enzyme, glucocerebrosidase, leading to the accumulation of glucocerebroside (GC). The relatively high prevalence of this disease within an ethnic group is believed to reflect a selective advantage. Treatment with enzyme replacement therapy (ERT) is safe and effective in ameliorating the primary symptoms of the disease, yet there have been reports that some patients on ERT have developed type 2 diabetes or metabolic syndrome, malignancies and central nervous system disorders. A series of animal studies suggest that these complications may be related to the reduction of GC levels by the enzyme administered. GC has been shown to have an immunomodulatory effect through the promotion of dendritic cells, natural killer T cells, and regulatory T cells. The break down of GC to ceramide can underline part of these findings. Clinical trials suggested a beneficial effect of GC in type 2 diabetes or nonalcoholic steatohepatitis. This review of the data from animal models and humans proposes that the increased level of GC may provide an evolutionary advantage for patients with GD. Indirectly, these data support treating symptomatic patients with mild/moderate GD with lowdose ERT and re-evaluating the use of ERT in asymptomatic patients.

show abstract

Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate

Cited by 354 publications

References 140 publications

Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond

Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond

Acid Ceramidase Expression Modulates the Sensitivity of A375 Melanoma Cells to Dacarbazine

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

Contact Info

Product

Resources

About