title: The enigma of ceramide synthase regulation in mammalian cells.
abstract: Ceramide synthases (CerS) are key enzymes in the lipid metabolism of eukaryotic cells. Their products, ceramides (Cer), are components of cellular membranes but also mediate signaling functions in physiological processes such as proliferation, skin barrier function and cerebellar development. In pathophysiological processes such as multiple sclerosis and tumor progression, ceramide levels are altered, which can be ascribed, partly, to dysregulation of CerS gene transcription. Most publications deal with the effects of altered ceramide levels on physiological and pathophysiological processes, but the regulation of the appropriate CerS is frequently not investigated. This is insufficient for the clarification of the role of ceramides, because most ceramide species are generated by at least two CerS. The mechanisms of CerS regulation are manifold and it seems that each CerS isoform is regulated individually. For this reason, we discuss the different CerS separately in this review. From transcriptional regulation to alteration of protein activity, the possibilities to influence CerS are diverse. Furthermore, CerS are influenced by a variety of molecules including hormones and lipids. Without claiming completeness, we provide a résumé of the regulatory mechanisms for each CerS in mammalian cells and how dysregulation of these mechanisms during physiological processes may lead to pathophysiological processes.
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann- Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: wegner@med.uni-frankfurt.de.
authors.forename: Marthe-Susanna
authors.initials: MS
authors.lastname: Wegner
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology (TMP), Frankfurt am Main, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schiffmann
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology (TMP), Frankfurt am Main, Germany.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Parnham
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann- Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann- Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Grösch
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000378:metabolism / Q000473:pathology; D057890:Epigenomics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D013107:Sphingolipids; D010088:Oxidoreductases; C108138:dihydroceramide desaturase
keywords: Ceramide synthases; Epigenetic; Post-translational; Regulation; Transcriptional; miR