Dihydroceramide Desaturase Activity is Modulated by Oxidative Stress

Overview

Journal Biochem J

Specialty Biochemistry

Date 2010 Jan 29

PMID 20105137

Citations 36

Authors

Jolanta Idkowiak-Baldys

Aintzane Apraiz

Li Li

Mehrdad Rahmaniyan

Christopher J Clarke

Jacqueline M Kraveka

Aintzane Asumendi

Yusuf A Hannun

Affiliations

Soon will be listed here.

Abstract

Oxidative stress has been implicated previously in the regulation of ceramide metabolism. In the present study, its effects on dihydroceramide desaturase were investigated. To stimulate oxidative stress, HEK (human embyronic kidney)-293, MCF7, A549 and SMS-KCNR cells were treated with H2O2, menadione or tert-butylhydroperoxide. In all cell lines, an increase in dihydroceramide was observed upon oxidative stress as measured by LC (liquid chromatography)/MS. In contrast, total ceramide levels were relatively unchanged. Mechanistically, dihydroceramide desaturase activity was measured by an in situ assay and decreased in a time- and dose-dependent fashion. Interestingly, no detectable changes in the protein levels were observed, suggesting that oxidative stress does not induce degradation of dihydroceramide desaturase. In summary, oxidative stress leads to potent inhibition of dihydroceramide desaturase resulting in significant elevation in dihydroceramide levels in vivo.

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References

Jiang Q, Wong J, Fyrst H, Saba J, Ames B . gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. Proc Natl Acad Sci U S A. 2004; 101(51):17825-30. PMC: 535585. DOI: 10.1073/pnas.0408340102. View

Signorelli P, Munoz-Olaya J, Gagliostro V, Casas J, Ghidoni R, Fabrias G . Dihydroceramide intracellular increase in response to resveratrol treatment mediates autophagy in gastric cancer cells. Cancer Lett. 2009; 282(2):238-43. DOI: 10.1016/j.canlet.2009.03.020. View

Hannun Y, Obeid L . Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008; 9(2):139-50. DOI: 10.1038/nrm2329. View

Ballatori N, Krance S, Notenboom S, Shi S, Tieu K, Hammond C . Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009; 390(3):191-214. PMC: 2756154. DOI: 10.1515/BC.2009.033. View

Applegate M, Humphries K, Szweda L . Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid. Biochemistry. 2007; 47(1):473-8. DOI: 10.1021/bi7017464. View

Michel C, van Echten-Deckert G, Rother J, Sandhoff K, Wang E, Merrill Jr A . Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide. J Biol Chem. 1997; 272(36):22432-7. DOI: 10.1074/jbc.272.36.22432. View

Chlebowski R, Dietrich M, Akman S, Block J . Vitamin K3 inhibition of malignant murine cell growth and human tumor colony formation. Cancer Treat Rep. 1985; 69(5):527-32. View

Schulze H, Michel C, van Echten-Deckert G . Dihydroceramide desaturase. Methods Enzymol. 1999; 311:22-30. DOI: 10.1016/s0076-6879(00)11063-8. View

McAmis W, Schaeffer Jr R, Baynes J, Wolf M . Menadione causes endothelial barrier failure by a direct effect on intracellular thiols, independent of reactive oxidant production. Biochim Biophys Acta. 2003; 1641(1):43-53. DOI: 10.1016/s0167-4889(03)00063-6. View

10.

Lovat P, Ranalli M, Corazzari M, Raffaghello L, Pearson A, Ponzoni M . Mechanisms of free-radical induction in relation to fenretinide-induced apoptosis of neuroblastoma. J Cell Biochem. 2003; 89(4):698-708. DOI: 10.1002/jcb.10551. View

11.

Darwiche N, Hatoum A, Dbaibo G, Kadara H, Nasr R, Abou-Lteif G . N-(4-hydroxyphenyl)retinamide induces growth arrest and apoptosis in HTLV-I-transformed cells. Leukemia. 2004; 18(3):607-15. DOI: 10.1038/sj.leu.2403245. View

12.

Kitatani K, Idkowiak-Baldys J, Hannun Y . The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell Signal. 2008; 20(6):1010-8. PMC: 2422835. DOI: 10.1016/j.cellsig.2007.12.006. View

13.

Szulc Z, Bielawski J, Gracz H, Gustilo M, Mayroo N, Hannun Y . Tailoring structure-function and targeting properties of ceramides by site-specific cationization. Bioorg Med Chem. 2006; 14(21):7083-104. DOI: 10.1016/j.bmc.2006.07.016. View

14.

Maceyka M, Milstien S, Spiegel S . Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling. J Lipid Res. 2008; 50 Suppl:S272-6. PMC: 2674705. DOI: 10.1194/jlr.R800065-JLR200. View

15.

Menon S, Goswami P . A redox cycle within the cell cycle: ring in the old with the new. Oncogene. 2006; 26(8):1101-9. DOI: 10.1038/sj.onc.1209895. View

16.

Geeraert L, Mannaerts G, Van Veldhoven P . Conversion of dihydroceramide into ceramide: involvement of a desaturase. Biochem J. 1997; 327 ( Pt 1):125-32. PMC: 1218771. DOI: 10.1042/bj3270125. View

17.

Tiwari M, Bajpai V, Sahasrabuddhe A, Kumar A, Sinha R, Behari S . Inhibition of N-(4-hydroxyphenyl)retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells. Carcinogenesis. 2008; 29(3):600-9. DOI: 10.1093/carcin/bgm264. View

18.

Kraveka J, Li L, Szulc Z, Bielawski J, Ogretmen B, Hannun Y . Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells. J Biol Chem. 2007; 282(23):16718-28. PMC: 2084375. DOI: 10.1074/jbc.M700647200. View

19.

Liu B, Andrieu-Abadie N, Levade T, Zhang P, Obeid L, Hannun Y . Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem. 1998; 273(18):11313-20. DOI: 10.1074/jbc.273.18.11313. View

20.

Chan C, Goldkorn T . Ceramide path in human lung cell death. Am J Respir Cell Mol Biol. 2000; 22(4):460-8. DOI: 10.1165/ajrcmb.22.4.3376. View