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Vol. 20, No. 4, 2007
Issue release date: June 2007
Section title: Original Paper
Skin Pharmacol Appl Skin Physiol 2007;20:187–194
(DOI:10.1159/000101388)

Kinetic Characteristics of Acidic and Alkaline Ceramidase in Human Epidermis

Houben E. · Uchida Y. · Nieuwenhuizen W.F. · De Paepe K. · Vanhaecke T. · Holleran W.M. · Rogiers V.
aDepartment of Toxicology, Dermato-Cosmetology and Pharmacognosy, Vrije Universiteit Brussel, Brussels, Belgium; bDepartment of Dermatology, University of California San Francisco and VA Medical Center, San Francisco, Calif., USA; cTNO Quality of Life, Zeist, The Netherlands

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 10/24/2006
Accepted: 12/22/2006
Published online: 3/29/2007

Number of Print Pages: 8
Number of Figures: 7
Number of Tables: 0

ISSN: 1660-5527 (Print)
eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP

Abstract

It has recently become evident that at least five ceramidase (CDase) isoforms are present in human epidermis, and that specifically acidic CDase (aCDase) and alkaline CDase (alkCDase) activities increase during keratinocyte differentiation, and thus might play a pivotal role(s) in permeability barrier function. Prior to investigating their possible roles in the epidermal barrier function, it is necessary to characterize basic kinetic parameters for these enzymes, as well as to determine the effects of the established CDase inhibitors and their activities. In this study, assays for both aCDase and alkCDase activities in fully differentiated human epidermis were optimized using a radiolabeled substrate. These studies revealed that aCDase activity is substantially higher than alkCDase activity, and that both isoenzymes are inhibited by a CDase inhibitor N-oleylethanolamine. These findings were also confirmed using an in situ enzyme assay.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 10/24/2006
Accepted: 12/22/2006
Published online: 3/29/2007

Number of Print Pages: 8
Number of Figures: 7
Number of Tables: 0

ISSN: 1660-5527 (Print)
eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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References

  1. He X, Li CM, Park JH, Dagan A, Gatt S, Schuchman EH: A fluorescence-based high-performance liquid chromatographic assay to determine acid ceramidase activity. Anal Biochem 1999;274:264–269.
  2. Linke T, Lansmann S, Sandhoff K: Purification of acid ceramidase from human placenta. Methods Enzymol 2000;311:201–207.
  3. Momoi T, Ben Yoseph Y, Nadler HL: Substrate-specificities of acid and alkaline ceramidases in fibroblasts from patients with Farber disease and controls. Biochem J 1982;205:419–425.
  4. Koch J, Gartner S, Li CM, Quintern LE, Bernardo K, Levran O, Schnabel D, Desnick RJ, Schuchman EH, Sandhoff K: Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification of the first molecular lesion causing Farber disease. J Biol Chem 1996;271:33110–33115.
  5. Zhang Z, Mandal AK, Mital A, Popescu N, Zimonjic D, Moser A, Moser H, Mukherjee AB: Human acid ceramidase gene: novel mutations in Farber disease. Mol Genet Metab 2000;70:301–309.
  6. El Bawab S, Roddy P, Qian T, Bielawska A, Lemasters JJ, Hannun YA: Molecular cloning and characterization of a human mitochondrial ceramidase. J Biol Chem 2000;275:21508–21513.
  7. Hwang YH, Tani M, Nakagawa T, Okino N, Ito M: Subcellular localization of human neutral ceramidase expressed in HEK293 cells. Biochem Biophys Res Commun 2005;331:37–42.
  8. Mao C, Xu R, Szulc ZM, Bielawska A, Galadari SH, Obeid LM: Cloning and characterization of a novel human alkaline ceramidase. A mammalian enzyme that hydrolyzes phytoceramide. J Biol Chem 2001;276:26577–26588.
  9. Mao C, Xu R, Szulc ZM, Bielawski J, Becker KP, Bielawska A, Galadari SH, Hu W, Obeid LM: Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. J Biol Chem 2003;278:31184–31191.
  10. Houben E, Holleran WM, Yaginuma T, Mao C, Obeid LM, Rogiers V, Takagi Y, Elias PM, Uchida Y: Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis. J Lipid Res 2006;47:1063–1070.
  11. Wakita H, Tokura Y, Yagi H, Nishimura K, Furukawa F, Takigawa M: Keratinocyte differentiation is induced by cell-permeant ceramides and its proliferation is promoted by sphingosine. Arch Dermatol Res 1994;286:350–354.
  12. Jung EM, Griner RD, Mann-Blakeney R, Bollag WB: A potential role for ceramide in the regulation of mouse epidermal keratinocyte proliferation and differentiation. J Invest Dermatol 1998;110:318–323.
  13. Gniadecki R, Gajkowska B, Bartosik J, Hansen M, Wulf HC: Variable expression of apoptotic phenotype in keratinocytes treated with ultraviolet radiation, ceramide, or suspended in semisolid methylcellulose. Acta Derm Venereol 1998;78:248–257.
  14. Bektas M, Dullin Y, Wieder T, Kolter T, Sandhoff K, Brossmer R, Ihrig P, Orfanos CE, Geilen CC: Induction of apoptosis by synthetic ceramide analogues in the human keratinocyte cell line HaCaT. Exp Dermatol 1998;7:342–349.
  15. Pillai S, Mahajan M, Carlomusto M: Ceramide potentiates, but sphingomyelin inhibits, vitamin D-induced keratinocyte differentiation: comparison between keratinocytes and HL-60 cells. Arch Dermatol Res 1999;291:284–289.
  16. Muller-Wieprecht V, Riebeling C, Stooss A, Orfanos CE, Geilen CC: Bcl-2 transfected HaCaT keratinocytes resist apoptotic signals of ceramides, tumor necrosis factor alpha and 1 alpha, 25-dihydroxyvitamin D3. Arch Dermatol Res 2000;292:455–462.
  17. Di Nardo A, Benassi L, Magnoni C, Cossarizza A, Seidenari S, Giannetti A: Ceramide 2 (N-acetyl sphingosine) is associated with reduction in Bcl-2 protein levels by Western blotting and with apoptosis in cultured human keratinocytes. Br J Dermatol 2000;143:491–497.
  18. Xia P, Wang L, Gamble JR, Vadas MA: Activation of sphingosine kinase by tumor necrosis factor-alpha inhibits apoptosis in human endothelial cells. J Biol Chem 1999;274:34499–34505.
  19. Manggau M, Kim DS, Ruwisch L, Vogler R, Korting HC, Schafer-Korting M, Kleuser B: 1α,25-dihydroxyvitamin D3 protects human keratinocytes from apoptosis by the formation of sphingosine-1-phosphate. J Invest Dermatol 2001;117:1241–1249.
  20. Vogler R, Sauer B, Kim DS, Schafer-Korting M, Kleuser B: Sphingosine-1-phosphate and its potentially paradoxical effects on critical parameters of cutaneous wound healing. J Invest Dermatol 2003;120:693–700.
  21. Sauer B, Vogler R, von Wenckstern H, Fujii M, Anzano MB, Glick AB, Schafer-Korting M, Roberts AB, Kleuser B: Involvement of Smad signaling in sphingosine 1-phosphate-mediated biological responses of keratinocytes. J Biol Chem 2004;279:38471–38479.
  22. Hammer S, Sauer B, Spika I, Schraut C, Kleuser B, Schafer-Korting M: Glucocorticoids mediate differential anti-apoptotic effects in human fibroblasts and keratinocytes via sphingosine-1-phosphate formation. J Cell Biochem 2004;91:840–851.
  23. Merrill AH, Wang E: Biosynthesis of long-chain (sphingoid) bases from serine by LM cells. Evidence for introduction of the 4-trans-double bond after de novo biosynthesis of N-acylsphinganine(s). J Biol Chem 1986;261:3764–3769.
  24. Rother J, van Echten G, Schwarzmann G, Sandhoff K: Biosynthesis of sphingolipids: dihydroceramide and not sphinganine is desaturated by cultured cells. Biochem Biophys Res Commun 1992;189:14–20.
  25. Elias PM, Menon GK: Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 1991;24:1–26.
  26. Elias PM, Feingold KR: Lipids and the epidermal water barrier: metabolism, regulation, and pathophysiology. Semin Dermatol 1992;11:176–182.
  27. Bibel DJ, Aly R, Shinefield HR: Topical sphingolipids in antisepsis and antifungal therapy. Clin Exp Dermatol 1995;20:395–400.
  28. Arikawa J, Ishibashi M, Kawashima M, Takagi Y, Ichikawa Y, Imokawa G: Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus. J Invest Dermatol 2002;119:433–439.
  29. Nieuwenhuizen WF, van Leeuwen S, Gotz F, Egmond MR: Synthesis of a novel fluorescent ceramide analogue and its use in the characterization of recombinant ceramidase from Pseudomonas aeruginosa PA01. Chem Phys Lipids 2002;114:181–191.
  30. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.
  31. Wertz PW, Downing DT: Ceramidase activity in porcine epidermis. FEBS Lett 1990;268:110–112.
  32. Yada Y, Higuchi K, Imokawa G: Purification and biochemical characterization of membrane-bound epidermal ceramidases from guinea pig skin. J Biol Chem 1995;270:12677–12684.
  33. Bernardo K, Hurwitz R, Zenk T, Desnick RJ, Ferlinz K, Schuchman EH, Sandhoff K: Purification, characterization, and biosynthesis of human acid ceramidase. J Biol Chem 1995;270:11098–11102.
  34. Behne MJ, Meyer JW, Hanson KM, Barry NP, Murata S, Crumrine D, Clegg RW, Gratton E, Holleran WM, Elias PM, Mauro TM: NHE1 regulates the stratum corneum permeability barrier homeostasis. Microenvironment acidification assessed with fluorescence lifetime imaging. J Biol Chem 2002;277:47399–47406.
  35. Behne MJ, Barry NP, Hanson KM, Aronchik I, Clegg RW, Gratton E, Feingold K, Holleran WM, Elias PM, Mauro TM: Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function. J Invest Dermatol 2003;120:998–1006.