Ceramide in Regulation of Apoptosis

Jaffrézou, Jean‐Pierre; Laurent, Guy; Levade, Thierry

doi:10.1007/0-306-47931-1_14

Cited by 15 publications

(7 citation statements)

References 76 publications

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“…To establish if A‐SMase mediated either effect, HSC were pretreated with SR33557, a potent A‐SMase inhibitor [23]. SR33557 prevented the increased phosphorylation of JNK as well as the decreased phosphorylation of p38 MAPK induced by TNF‐α (Fig.…”

Section: Resultsmentioning

confidence: 99%

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells¹

et al. 2002

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The role of members of the mitogen-activated protein kinase (MAPK) family on tumor necrosis factor K K (TNF-K K)-mediated down-regulation of col1a1 gene was studied. TNF-K K increased extracellular-regulated kinase and Jun-N-terminal kinase phosphorylation, but these e¡ects were not related to its inhibitory e¡ect on K K1(I) procollagen (col1a1) mRNA levels. Phosphorylation of p38 MAPK was decreased in response to TNF-K K, and the speci¢c p38 MAPK inhibitor SB203580 mimicked the e¡ect of TNF-K K on col1a1 mRNA levels. Transforming growth factor L L (TGF-L L) increased p38 MAPK phosphorylation and SB203580 prevented the induction of col1a1 mRNA levels by TGF-L L. These results suggest that p38 MAPK plays an important role in regulating the expression of col1a1 in hepatic stellate cells in response to cytokines. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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Section: Resultsmentioning

confidence: 99%

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells¹

et al. 2002

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“…[3][4][5][6][7][8]. Therefore, it has been hypothesized that the cellular role of SM synthase goes beyond the production of SM.…”

Section: Sphingomyelin (Sm)mentioning

confidence: 99%

Purification, Characterization, and Identification of a Sphingomyelin Synthase from Pseudomonas aeruginosa

Luberto

Stonehouse

Collins

et al. 2003

Journal of Biological Chemistry

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Sphingomyelin synthase is the enzyme that synthesizes sphingomyelin (SM) in mammalian cells by transferring a phosphorylcholine moiety from phosphatidylcholine to ceramide. Despite its importance, the gene and/or the protein responsible for this activity has not yet been identified. Here we report the purification, identification, and biochemical characterization of an enzymatic activity that synthesizes SM in Pseudomonas aeruginosa. SM synthase-like activity was found secreted in the culture medium of P. aeruginosa, strains PA01 and PAK, whereas it could not be detected in cultures of Escherichia coli. From the medium of PAK cultures, SM synthase was purified through sequential chromatographic columns. After separation on polyacrylamide-SDS gels and visualization by silver staining, the purified enzyme showed two bands, one of ϳ75 kDa and one of 30 -35 kDa. Interestingly, the highly purified SM synthase preparation also showed neutral sphingomyelinase activity. We therefore investigated whether the protein we purified as SM synthase could actually be the previously identified PlcH, a 78-kDa phospholipase C known to hydrolyze phosphatidylcholine and SM in P. aeruginosa. First, the purified SM synthase preparation contained a 78-kDa protein that reacted with monoclonal antibodies raised against purified PlcH. Second, purified PlcH showed SM synthase activity. Third, using different knockout mutant strains for the PlcH operon, PlcH was found to be necessary for SM synthase activity in P. aeruginosa. Interestingly, SM synthase activity was specific to the Pseudomonas PlcH as other bacterial phospholipases did not display SM synthase activity. Biochemical studies on the Pseudomonas SM synthase confirmed that it is a transferase, similar to the mammalian enzyme, that specifically recognizes the choline head-group and the primary hydroxyl on ceramide. This SM synthase did not have reverse transferase activity. In conclusion, the Pseudomonas PlcH also exerts SM synthase activity; therefore, for the first time, we have identified a structural gene for a SM synthase.

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“…The ceramide has been recognized as an important second messager implicated in triggering apoptotic/necrotic processes in many normal and cancer cell types [1–14]. Several works have been carried out to establish the molecular mechanisms by which this endogenous sphingolipid mediates its biological effects.…”

Section: Introductionmentioning

confidence: 99%

“…Several works have been carried out to establish the molecular mechanisms by which this endogenous sphingolipid mediates its biological effects. In particular, the subcellular localization of ceramide molecules in plasmalemmal microdomains termed caveolae or rafts, lysosomes and mitochondria represents an important factor that determines their cellular functions [11,13–20]. Moreover, the cellular ceramide generation induced by different external agents such as tumor necrosis factor‐α (TNF‐α), Fas ligand, interferon‐γ (INF‐γ) and interleukin‐1β (IL‐1β) through the activation of their transmembrane receptors might lead to the modulation of the activities of different protein kinases and phosphatases that regulate certain phases of apoptotic/necrotic cell death [21–30].…”

Section: Introductionmentioning

confidence: 99%

New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer

Mimeault

2002

FEBS Letters

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Recent data on the cellular ceramide functions and its involvement in the apoptotic/necrotic cell death as well as its anticarcinogenic properties are presented. The emphasis is on the connections between the ceramide and caspase signaling pathways during the apoptotic cell death process. Notably, the experimental strategies and pharmacological tools used for establishment of the role of ceramide in triggering cell death are described. Moreover, the importance of a compartmentation of endogenous ceramide within the plasma membrane microdomains, lysosomes and mitochondria is discussed. Information on the deregulated functions of ceramide and caspase signaling pathways in several metastatic cancer types is also presented.

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Ceramide in Regulation of Apoptosis

Cited by 15 publications

References 76 publications

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells¹

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells¹

Purification, Characterization, and Identification of a Sphingomyelin Synthase from Pseudomonas aeruginosa

New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer

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Ceramide in Regulation of Apoptosis

Cited by 15 publications

References 76 publications

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells1

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells1

Purification, Characterization, and Identification of a Sphingomyelin Synthase from Pseudomonas aeruginosa

New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer

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Product

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p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells¹

p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF‐α and TGF‐β in a cell line of rat hepatic stellate cells¹