Abstract
Ceramide, a bioactive lipid, has been extensively studied and identified as an essential bioactive molecule in mediating cellular signaling pathways. Sphingomyelinase (SMase), (EC 3.1.4.12) catalyzes the cleavage of the phosphodiester bond in sphingomyelin (SM) to form ceramide and phosphocholine. In mammals, three Mg2+-dependent neutral SMases termed nSMase1, nSMase2 and nSMase3 have been identified. Among the three enzymes, nSMase2 is the most studied and has been implicated in multiple physiological responses including cell growth arrest, apoptosis, development and inflammation. In this review, we summarize recent findings for the cloned nSMases and discuss the insights for their roles in regulation ceramide metabolism and cellular signaling pathway.
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Abbreviations
- SMase:
-
Sphingomyelinase
- nSMase:
-
Neutral sphingomyelinase
- SM:
-
Sphingomyelin
- IL:
-
Interleukin
- ER:
-
Endoplasmic reticulum
- ROS:
-
Reactive oxygen species
- HAE:
-
Human airway epithelial
- TNF:
-
Tumor necrosis factor. GSH, glutathione
- FAN:
-
Factor associated with N-SMase activation
- VCAM:
-
Vascular cell adhesion molecule-1
- ICAM:
-
Intercellular adhesion molecule-1
- eNOS:
-
Endothelial nitric oxide synthase
- LPS:
-
Lipopolysaccharide
- IL-1β:
-
Interleukin 1-beta
- IRAK:
-
IL-1β receptor-associated kinase
- KO:
-
Knockout
- PM:
-
Plasma membrane
- AD:
-
Alzheimer’s disease
- Aβ:
-
Amyloid-β peptide
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This work was supported in part by NIH grant GM43825.
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Wu, B.X., Clarke, C.J. & Hannun, Y.A. Mammalian Neutral Sphingomyelinases: Regulation and Roles in Cell Signaling Responses. Neuromol Med 12, 320–330 (2010). https://doi.org/10.1007/s12017-010-8120-z
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DOI: https://doi.org/10.1007/s12017-010-8120-z