Free Sphingosine Formation from Endogenous Substrates by a Liver Plasma Membrane System with a Divalent Cation Dependence and a Neutral pH Optimum

Slife, Charles W.; Wang, E.; Hunter, Robert L.; Wang, Sijian; Burgess, C.; Liotta, Dennis; Merrill, Alfred H.

doi:10.1016/s0021-9258(18)81629-5

Cited by 101 publications

(2 citation statements)

References 37 publications

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“…Lipids were extracted from equal amounts of protein from microsomes with the method of Bligh and Dyer (4). The lipids were dried under nitrogen gas, applied in 50 µl of chloroform-methanol (2:1) to silica LK5D plates, and developed in chloroform-methanol-petroleum ether-acetic acid-boric acid [40:20:30:10:1.8 vol/vol (44)]. After each plate was dried in a fume hood, the sample lanes and phospholipid standard lanes were briefly exposed to iodine vapors.…”

Section: Methodsmentioning

confidence: 99%

TNF-α increases ceramide without inducing apoptosis in alveolar type II epithelial cells

Mallampalli

Peterson

Carter

et al. 1999

American Journal of Physiology-Lung Cellular and Molecular Phys

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Ceramide is a bioactive lipid mediator that has been observed to induce apoptosis in vitro. The purpose of this study was to determine whether endogenous ceramide, generated in response to in vivo administration of tumor necrosis factor-α (TNF-α), increases apoptosis in primary rat alveolar type II epithelial cells. Intratracheal instillation of TNF-α (5 μg) produced a decrease in sphingomyelin and activation of a neutral sphingomyelinase. These changes were associated with a significant increase in lung ceramide content. TNF-α concomitantly activated the p42/44 extracellular signal-related kinases and induced nuclear factor-κB activation in the lung. Hypodiploid nuclei studies revealed that intratracheal TNF-α did not increase type II cell apoptosis compared with that in control cells after isolation. A novel observation from separate in vitro studies demonstrated that type II cells undergo a gradual increase in apoptosis after time in culture, a process that was accelerated by exposure of cells to ultraviolet light. However, culture of cells with a cell-permeable ceramide, TNF-α, or a related ligand, anti-CD95, did not increase apoptosis above the control level. The results suggest that ceramide resulting from TNF-α activation of sphingomyelin hydrolysis might activate the mitogen-activated protein kinase and nuclear factor-κB pathways without increasing programmed cell death in type II cells.

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Section: Methodsmentioning

confidence: 99%

TNF-α increases ceramide without inducing apoptosis in alveolar type II epithelial cells

Mallampalli

Peterson

Carter

et al. 1999

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Sphingosine, the substrate of hSK1, is concentrated in the plasma membrane (23). Therefore, one possible mechanism…”

Section: Phosphorylation and Plasma Membrane Localization Of Hsk1 Enhances S1p Generationmentioning

confidence: 99%

Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling

Pitson

Xia

Leclercq

et al. 2004

The Journal of Experimental Medicine

251

256

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Sphingosine kinase (SK) 1 catalyzes the formation of the bioactive lipid sphingosine 1-phosphate, and has been implicated in several biological processes in mammalian cells, including enhanced proliferation, inhibition of apoptosis, and oncogenesis. Human SK (hSK) 1 possesses high instrinsic catalytic activity which can be further increased by a diverse array of cellular agonists. We have shown previously that this activation occurs as a direct consequence of extracellular signal–regulated kinase 1/2–mediated phosphorylation at Ser225, which not only increases catalytic activity, but is also necessary for agonist-induced translocation of hSK1 to the plasma membrane. In this study, we report that the oncogenic effects of overexpressed hSK1 are blocked by mutation of the phosphorylation site despite the phosphorylation-deficient form of the enzyme retaining full instrinsic catalytic activity. This indicates that oncogenic signaling by hSK1 relies on a phosphorylation-dependent function beyond increasing enzyme activity. We demonstrate, through constitutive localization of the phosphorylation-deficient form of hSK1 to the plasma membrane, that hSK1 translocation is the key effect of phosphorylation in oncogenic signaling by this enzyme. Thus, phosphorylation of hSK1 is essential for oncogenic signaling, and is brought about through phosphorylation-induced translocation of hSK1 to the plasma membrane, rather than from enhanced catalytic activity of this enzyme.

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Rapid screening of specific changes in mRNA in thyroid carcinomas by sequence specific-differential display: Decreased expression of acid ceramidase mRNA in malignant and benign thyroid tumors

et al. 1999

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Sequence specific‐differential display (SS‐DD) is a powerful method for screening significant changes in gene expression between normal and malignant tissues. Using this method, we detected 3 genes for which the expression is much decreased in thyroid tumors. After sub‐cloning and sequencing analysis, one of the genes was revealed to be acid ceramidase (AC). The expression of AC in normal thyroids and thyroid tumors was examined by semi‐quantitative reverse‐transcription‐polymerase‐chain‐reaction (RT‐PCR). Obvious decreases in the expression of AC mRNA were observed in 5/6 follicular adenomas, 2/2 adenomatous goiters, 3/6 papillary carcinomas and 1/2 follicular carcinomas. To confirm this result, real‐time quantitative PCR analysis (TaqMan PCR) was carried out. The relative expression level of AC mRNA compared with that of GAPDH mRNA was reduced in follicular adenomas, follicular carcinomas, and papillary carcinomas. Further, the expression of AC mRNA was extremely reduced in 2 anaplastic carcinomas. These results suggest a possible relationship between thyroid tumorigenesis and the expression of AC mRNA. Moreover, the increased expression of AC mRNA in normal thyroid tissues suggests some fundamental roles of AC in thyroid function. Int. J. Cancer 81:700–704, 1999. © 1999 Wiley‐Liss, Inc.

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Free Sphingosine Formation from Endogenous Substrates by a Liver Plasma Membrane System with a Divalent Cation Dependence and a Neutral pH Optimum

Cited by 101 publications

References 37 publications

TNF-α increases ceramide without inducing apoptosis in alveolar type II epithelial cells

TNF-α increases ceramide without inducing apoptosis in alveolar type II epithelial cells

Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling

Rapid screening of specific changes in mRNA in thyroid carcinomas by sequence specific-differential display: Decreased expression of acid ceramidase mRNA in malignant and benign thyroid tumors

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