The yins and yangs of ceramide

Sharma, Kamal; Shi, Yufang

doi:10.1038/sj.cr.7290001

Cited by 17 publications

(10 citation statements)

References 50 publications

(73 reference statements)

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“…It was critical that the insertion of the capillary into the cell and the subsequent electrochemical-induced injection of the kit components did not interrupt the cellular activity, so that the assays of the intracellular glucose levels and SMase activity were meaningful. Because calcium is involved in multiple cellular pathways, the fluctuations in SMase activity or glucose concentrations should be associated with the changes in the intracellular calcium concentrations (32). Therefore, the intracellular calcium concentrations were measured using the fluorescence probe Fluo-3 before and after capillary insertion and the initial voltage application.…”

Section: Resultsmentioning

confidence: 99%

Nanokit for single-cell electrochemical analyses

Pan

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

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The development of more intricate devices for the analysis of small molecules and protein activity in single cells would advance our knowledge of cellular heterogeneity and signaling cascades. Therefore, in this study, a nanokit was produced by filling a nanometersized capillary with a ring electrode at the tip with components from traditional kits, which could be egressed outside the capillary by electrochemical pumping. At the tip, femtoliter amounts of the kit components were reacted with the analyte to generate hydrogen peroxide for the electrochemical measurement by the ring electrode. Taking advantage of the nanotip and small volume injection, the nanokit was easily inserted into a single cell to determine the intracellular glucose levels and sphingomyelinase (SMase) activity, which had rarely been achieved. High cellular heterogeneities of these two molecules were observed, showing the significance of the nanokit. Compared with the current methods that use a complicated structural design or surface functionalization for the recognition of the analytes, the nanokit has adapted features of the well-established kits and integrated the kit components and detector in one nanometer-sized capillary, which provides a specific device to characterize the reactivity and concentrations of cellular compounds in single cells.

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Section: Resultsmentioning

confidence: 99%

Nanokit for single-cell electrochemical analyses

Pan

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

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“…The membrane-bound enzyme neutral sphingomyelinase 2 (nSMase2), encoded by the sphingomyelin phosphodiesterase 3 (Smpd3) gene, cleaves sphingomyelin to generate the lipid second messenger ceramide, which affects a variety of cellular process, including proliferation, apoptosis, and differentiation (31)(32)(33)(34). A deletion mutation in the Smpd3 gene was identified in fragilitas ossium (fro), a mouse model of osteogenesis imperfecta (35).…”

Section: Although Bone Morphogenic Protein (Bmp) Signaling Promotes Cmentioning

confidence: 99%

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Kakoi

Maeda

Shinohara

et al. 2014

Journal of Biological Chemistry

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Background: It is not clear how BMP-induced chondrocyte maturation is cell-autonomously terminated. Results: BMP-2 induced the ceramide-generating enzyme neutral sphingomyelinase 2 (nSMase2) in chondrocytes, whereas silencing of nSMase2 enhanced maturation in an Akt signaling-dependent manner. Conclusion: nSMase2 signaling regulates BMP-induced chondrocyte maturation as a negative feedback mechanism. Significance: This study elucidated the novel link between BMP and lipid signaling in chondrogenesis.

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“…These interactions imply that ceramide or its metabolites might suppress a suppressor of the MAPK/ERK survival pathway such that removal of spt would reduce dSor1 and rolled hyperactivation. A candidate for this might be the transforming growth factor b (TGFb)-activated kinase 1 homolog TAK1, which is activated by ceramide and regulates both the JNK pathway in flies (Takatsu et al 2000) and the MAPK/ERK pathway (Sharma and Shi 1999;Zhang and Dong 2007). Alternatively, a sphingolipid metabolite might activate the presumptive ras/raf initiator of this pathway (Raabe 2000), such that removing spt would turn down signaling.…”

Section: Life Death and Sphingolipidsmentioning

confidence: 99%

Roles of sphingolipids in Drosophila development and disease

Kraut

2011

Journal of Neurochemistry

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response element binding protein; TAG, triacylglycerol; TGFa, transforming growth factor a. AbstractThe last 10 years have seen a rebirth of interest in lipid biology in the fields of Drosophila development and neurobiology, and sphingolipids have emerged as controlling many processes that have not previously been studied from the viewpoint of lipid biochemistry. Mutations in sphingolipid regulatory enzymes have been pinpointed as affecting cell survival and growth in tissues ranging from muscle to retina. Specification of cell types are also influenced by sphingolipid regulatory pathways, as genetic interactions of glycosphingolipid biosynthetic enzymes with many well-known signaling receptors such as Notch and epidermal growth factor receptor reveal. Furthermore, studies in flies are now uncovering unexpected roles of sphingolipids in controlling lipid storage and response to nutrient availability. The sophisticated genetics of Drosophila is particularly well suited to uncover the roles of sphingolipid regulatory enzymes in development and metabolism, especially in light of conserved pathways that are present in both flies and mammals. The challenges that remain in the field of sphingolipid biology in Drosophila are to combine traditional developmental genetics with more analytical biochemical and biophysical methods, to quantify and localize the responses of these lipids to genetic and metabolic perturbations.

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The yins and yangs of ceramide

Cited by 17 publications

References 50 publications

Nanokit for single-cell electrochemical analyses

Nanokit for single-cell electrochemical analyses

Bone Morphogenic Protein (BMP) Signaling Up-regulates Neutral Sphingomyelinase 2 to Suppress Chondrocyte Maturation via the Akt Protein Signaling Pathway as a Negative Feedback Mechanism

Roles of sphingolipids in Drosophila development and disease

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