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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/24 03:05:16」(JST)

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Ceramidase (EC 3.5.1.23, acylsphingosine deacylase, glycosphingolipid ceramide deacylase) is an enzyme which cleaves fatty acids from ceramide, producing sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate (S1P).^[1]

Function

Ceramide, SPH, and S1P are bioactive lipids that mediate cell proliferation, differentiation, apoptosis, adhesion, and migration. Presently, 7 human ceramidases encoded by 7 distinct genes have been cloned:^[1]

acid ceramidase (ASAH1) – cell survival
neutral ceramidase (ASAH2, ASAH2B, ASAH2C) – protective against inflammatory cytokines
alkaline ceramidase 1 (ACER1) – mediating cell differentiation by controlling the generation of SPH and S1P
alkaline ceramidase 2 (ACER2) – important for cell proliferation and survival
alkaline ceramidase 3 (ACER3)

Clinical significance

A deficiency in ASAH1 is associated with Farber disease.

References

^ ^a ^b Mao C, Obeid LM (September 2008). "Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate". Biochim. Biophys. Acta 1781 (9): 424–34. doi:10.1016/j.bbalip.2008.06.002. PMC 2614331. PMID 18619555.

External links

Ceramidase at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 3.5.1.23

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English Journal

Amyloid β-Peptide 1-42 Modulates the Proliferation of Mouse Neural Stem Cells: Upregulation of Fucosyltransferase IX and Notch Signaling.

Itokazu Y, Yu RK.Author information Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, Georgia Regents University, Augusta, GA, 30912, USA.AbstractAmyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer's disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarification of their physiological function is an important topic. We have systematically evaluated the effects of several putative bioactive Aβs (Aβ1-40, Aβ1-42, and Aβ25-35) on NSC proliferation. Treatment of NSCs with Aβ1-42 significantly increased the number of those cells (149 ± 10 %). This was not observed with Aβ1-40 which did not have any effects on the proliferative property of NSC. Aβ25-35, on the other hand, exhibited inhibitory effects on cellular proliferation. Since cell surface glycoconjugates, such as glycolipids, glycoproteins, and proteoglycans, are known to be important for maintaining cell fate determination, including cellular proliferation, in NSCs and they undergo dramatic changes during differentiation, we examined the effect of Aβs on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that Aβ1-42 altered the expression of several key glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9), sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the Lewis X carbohydrate epitope, which is known to be expressed in stem cells. Aβ1-42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Aβ1-42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.
Molecular neurobiology.Mol Neurobiol.2014 Jan 17. [Epub ahead of print]
Amyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer's disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarifica
PMID 24436056

Prostate cell lines as models for biomarker discovery: Performance of current markers and the search for new biomarkers.

Johnson IR, Parkinson-Lawrence EJ, Butler LM, Brooks DA.Author information Mechanisms in Cell Biology and Disease Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.AbstractBACKGROUND: Prostate cancer cell lines have been used in the search for biomarkers that are suitable for prostate cancer diagnosis. Unfortunately, many cell line studies have only involved single cell lines, partially characterized cell lines or were performed without controls, and this may have been detrimental to effective biomarker discovery. We have analyzed a panel of prostate cancer and nonmalignant control cell lines using current biomarkers and then investigated a set of prospective endosomal and lysosomal proteins to search for new biomarkers.
The Prostate.Prostate.2014 Jan 16. doi: 10.1002/pros.22777. [Epub ahead of print]
BACKGROUND: Prostate cancer cell lines have been used in the search for biomarkers that are suitable for prostate cancer diagnosis. Unfortunately, many cell line studies have only involved single cell lines, partially characterized cell lines or were performed without controls, and this may have bee
PMID 24435746

Sphingomyelin synthase-related protein SMSr is a suppressor of ceramide-induced mitochondrial apoptosis.

Tafesse FG, Vacaru AM, Bosma EF, Hermansson M, Jain A, Hilderink A, Somerharju P, Holthuis JC.Author information Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, the Netherlands.AbstractCells synthesize ceramides in the endoplasmic reticulum (ER) as precursors for sphingolipids to form an impermeable plasma membrane. As ceramides are engaged in apoptotic pathways, cells would need to monitor their levels closely to avoid killing themselves during sphingolipid biosynthesis. How this is accomplished remains to be established. Here we identify SMSr (SAMD8), an ER-resident ceramide phosphoethanolamine (CPE) synthase, as a suppressor of ceramide-mediated cell death. Disruption of SMSr catalytic activity causes a rise in ER ceramides and their mislocalization to mitochondria, triggering a mitochondrial pathway of apoptosis. Blocking de novo ceramide synthesis, stimulating ceramide export from the ER or targeting a bacterial ceramidase to mitochondria rescues SMSr-deficient cells from apoptosis. We also show that SMSr-catalyzed CPE production, although essential, is not sufficient to suppress ceramide-induced cell death and that SMSr-mediated ceramide homeostasis requires the N-terminal sterile α-motif, or SAM domain, of the enzyme. These results define ER ceramides as bona fide transducers of mitochondrial apoptosis and indicate a primary role of SMSr in monitoring ER ceramide levels to prevent inappropriate cell death during sphingolipid biosynthesis.
Journal of cell science.J Cell Sci.2014 Jan 15;127(Pt 2):445-54. doi: 10.1242/jcs.138933. Epub 2013 Nov 20.
Cells synthesize ceramides in the endoplasmic reticulum (ER) as precursors for sphingolipids to form an impermeable plasma membrane. As ceramides are engaged in apoptotic pathways, cells would need to monitor their levels closely to avoid killing themselves during sphingolipid biosynthesis. How this
PMID 24259670

Japanese Journal

Role of down-regulated neutral ceramidase during all-trans retinoic acid-induced neuronal differentiation in SH-SY5Y neuroblastoma cells

Tanaka Kouji,Tamiya-Koizumi Keiko,Hagiwara Kazumi [他]
Journal of Biochemistry 151(6), 611-620, 2012-06
NAID 40019309972

My journey into the world of sphingolipids and sphingolipidoses

SANDHOFF Konrad
Proceedings of the Japan Academy, Series B 88(10), 554-582, 2012
… Purification of lysosomal acid sphingomyelinase and ceramidase and analysis of their gene structures were the prerequisites for the clarification of Niemann-Pick and Farber disease. … Biosynthesis and intracellular trafficking of lysosomal hydrolases (hexosaminidases, acid sphingomyelinase and ceramidase) and lipid binding and transfer proteins (GM2 activator, saposins) were analyzed to identify the molecular and metabolic basis of several sphingolipidoses. …
NAID 130002540350

The Mucin Box and Signal/Anchor Sequence of Rat Neutral Ceramidase Recruit Bacterial Sphingomyelinase to the Plasma Membrane

Nakagawa Tetsuto,Tani Motohiro,Sueyoshi Noriyuki [他],ITO Makoto
Bioscience, biotechnology, and biochemistry 75(5), 987-990, 2011-05-23
… We found that the mucin box and signal/anchor sequence of a rat neutral ceramidase recruit bacterial sphingomyelinase to the plasma membranes of mammalian cells. …
NAID 10028272935

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★リンクテーブル★

リンク元	「セラミダーゼ」「セラミド分解酵素」
拡張検索	「glucosylceramidase」「glucosylceramidase deficiency」「galactosylceramidase」「glycosylceramidase」