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Involvement of acid ceramidase in the degradation of bioactive N-acylethanolamines.
- Source :
-
Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2021 Sep; Vol. 1866 (9), pp. 158972. Date of Electronic Publication: 2021 May 24. - Publication Year :
- 2021
-
Abstract
- Bioactive N-acylethanolamines (NAEs) include palmitoylethanolamide, oleoylethanolamide, and anandamide, which exert anti-inflammatory, anorexic, and cannabimimetic actions, respectively. The degradation of NAEs has been attributed to two hydrolases, fatty acid amide hydrolase and NAE acid amidase (NAAA). Acid ceramidase (AC) is a lysosomal enzyme that hydrolyzes ceramide (N-acylsphingosine), which resembles NAAA in structure and function. In the present study, we examined the role of AC in the degradation of NAEs. First, we demonstrated that purified recombinant human AC can hydrolyze various NAEs with lauroylethanolamide (C12:0-NAE) as the most reactive NAE substrate. We then used HEK293 cells metabolically labeled with [ <superscript>14</superscript> C]ethanolamine, and revealed that overexpressed AC lowered the levels of <superscript>14</superscript> C-labeled NAE. As analyzed with liquid chromatography-tandem mass spectrometry, AC overexpression decreased the amounts of different NAE species. Furthermore, suppression of endogenous AC in LNCaP prostate cells by siRNA increased the levels of various NAEs. Lastly, tissue homogenates from mice genetically lacking saposin D, a presumable activator protein of AC, showed much lower hydrolyzing activity for NAE as well as ceramide than the homogenates from wild-type mice. These results demonstrate the ability of AC to hydrolyze NAEs and suggest its physiological role as a third NAE hydrolase.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Animals
HEK293 Cells
Mice
Palmitic Acids metabolism
Oleic Acids metabolism
Endocannabinoids metabolism
Amides metabolism
Polyunsaturated Alkamides metabolism
Arachidonic Acids metabolism
Hydrolysis
Male
Ceramides metabolism
Amidohydrolases
Ethanolamines metabolism
Acid Ceramidase metabolism
Acid Ceramidase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-2618
- Volume :
- 1866
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular and cell biology of lipids
- Publication Type :
- Academic Journal
- Accession number :
- 34033896
- Full Text :
- https://doi.org/10.1016/j.bbalip.2021.158972