Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P

Xu, Ruijuan; Jin, Junfei; Hu, Wei; Sun, Wei; Bielawski, Jacek; Szulc, Zdzisław M.; Taha, Tarek; Obeid, Lina M.; Mao, Cungui

doi:10.1096/fj.05-5689com

Cited by 129 publications

(189 citation statements)

References 49 publications

(64 reference statements)

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“…To overexpress ACER2, we used the stable cell line HeLa T-Rex/ACER2 that we constructed in our previous study ( 17 ). To overexpress ACER1, we applied the same expression system.…”

Section: Overexpression Of Hacer2 and Macer1mentioning

confidence: 99%

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Casasampere

Camacho

Cingolani

et al. 2015

Journal of Lipid Research

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“…To overexpress ACER2, we used the stable cell line HeLa T-Rex/ACER2 that we constructed in our previous study ( 17 ). To overexpress ACER1, we applied the same expression system.…”

Section: Overexpression Of Hacer2 and Macer1mentioning

confidence: 99%

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Casasampere

Camacho

Cingolani

et al. 2015

Journal of Lipid Research

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“…Inhibition of NBD-GlcCer synthesis by PPMP in the present study and by tamoxifen (14) enhanced the formation of NBD-SM in CHO cells and in COS cells, respectively. MAPPsensitive alkaline ceramidases such as ACER2 and ACER3 are localized to the Golgi apparatus (39,49). In this study, we showed that Na 3 VO 4 induced formation of NBD-caproic acid (and NBD-C1P) for 2 h accompanied by a decrease in NBD-SM, and the expression of hCERK by itself decreased the level of NBD-caproic acid.…”

Section: Characteristics Of Nbd-ceramide Metabolism With or Without Nmentioning

confidence: 56%

Activation of Ceramidase and Ceramide Kinase by Vanadate via a Tyrosine Kinase–Mediated Pathway

Tada¹,

Toyomura²,

Nakamura³

et al. 2010

J Pharmacol Sci

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Abstract. Ceramide, a key molecule in the metabolism of sphingolipids, is converted by ceramidase to sphingosine, and phosphorylated by ceramide kinase to form ceramide-1-phosphate (C1P). In this study, we improved on a method of thin-layer chromatography using a fluorescent ceramide, 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-ceramide) by adding another step for separation of extracted ceramide metabolites by lipophilicity, and determined levels of C1P, caproic acid, sphingomyelin, and glucosylceramide simultaneously. Also we found that 1) treatment of NBD-ceramide-labeled cells (human lung adenocarcinoma A549 cells and Chinese hamster ovary cells) with Na 3 VO 4 increased the amount of NBD-C1P formed within 30 min, 2) the treatment increased production of NBD-caproic acid, a counterpart of sphingosine, by ceramidase within 2 h, 3) expression of ceramide kinase enhanced the Na 3 VO 4 -induced formation of NBD-C1P, and tyrosine kinase inhibitors (herbimycin and genistein) decreased the response, 4) the production of NBD-caproic acid in A549 cells was inhibited by genistein, and 5) the responses for 2 h after Na 3 VO 4 treatment were accompanied by a decrease in the production of NBD-sphingomyelin, not a loss of NBD-ceramide. The improved thin-layer chromatography method was useful for the simultaneous determination of enzymatic activities for ceramide metabolism in cells.

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“…Thus, deacylation of short-chain ceramide is suggested to occur at the intact Golgi apparatus. Mao's group has recently cloned a novel human alkaline ceramidase (termed alkaline ceramidase 2) which selectively localizes to the Golgi apparatus [58]. In light of the Golgi-dependent deacylation of short-chain ceramide, alkaline ceramidase 2 might play a role in deacylation of short-chain ceramide and resultant release of free sphingosine.…”

Section: -3 Deacylation/reacylation Of Exogenous Short-chain Ceramidementioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

520

457

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Sphingolipids are important components of eukaryotic cells, many of which function as bioactive signaling molecules. Of these, ceramide is a central metabolite and plays key roles in a variety of cellular responses, including regulation of cell growth, viability, differentiation, and senescence. Ceramide is composed of the long-chain sphingoid base, sphingosine, in N-linkage to a variety of acyl groups. Sphingosine serves as the product of sphingolipid catabolism, and it is mostly salvaged through re-acylation, resulting in the generation of ceramide or its derivatives. This recycling of sphingosine is termed the "salvage pathway", and recent evidence points to important roles for this pathway in ceramide metabolism and function. A number of enzymes are involved in the salvage pathway, and these include sphingomyelinases, cerebrosidases, ceramidases, and ceramide synthases. Recent studies suggest that the salvage pathway is not only subject to regulation, but it also modulates the formation of ceramide and subsequent ceramide-dependent cellular signals. This review focuses on the salvage pathway in ceramide metabolism, its regulation, its experimental analysis, and emerging biological functions.

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Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P

Cited by 129 publications

References 49 publications

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Activation of Ceramidase and Ceramide Kinase by Vanadate via a Tyrosine Kinase–Mediated Pathway

The sphingolipid salvage pathway in ceramide metabolism and signaling

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