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Event: 2023

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Inhibition of Ceramide Synthase

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Inhibition CerS
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
CerS leads to NTDs MolecularInitiatingEvent Lola Bajard (send email) Open for citation & comment

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Ceramide synthases (CerS) are enzymes that catalyze the acylation of Sphiganine (Sa) to form (dihydro-)ceramide (a precursor for ceramide and complex sphingolipds) and also the reacylation of Sphingosine (So) that is derived from the turnover of complex sphingolipids (EFSA et al., 2018; Sassa et al., 2016). Six mammalian isoforms of ceramide synthases exist (CerS1–6), which differ in their tissue distribution as well as in their specificity of the fatty acid chain length used for N-acylation (EFSA et al., 2018; Stiban et al., 2010; Tidhar and Futerman, 2013). The inhibition of CerS results in an increase of Sa, So, and, often, Sa/So ratio. Among others, two possible effects of CerS inhibition are 1) a decrease in the level of ceramides and complex sphingolipids (Riley and Merrill, 2019) and 2) an increase in the phosphorylated forms of Sa and So (Gelineau-van Waes et al., 2012).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

EFSA, Knutsen, H.K., Barregård, L., Bignami, M., Brüschweiler, B., Ceccatelli, S., Cottrill, B., Dinovi, M., Edler, L., Grasl-Kraupp, B., Hogstrand, C., Hoogenboom, L. (Ron), Nebbia, C.S., Petersen, A., Rose, M., Roudot, A.C., Schwerdtle, T., Vleminckx, C., Vollmer, G., Wallace, H., Dall’Asta, C., Gutleb, A.C., Humpf, H.U., Galli, C., Metzler, M., Oswald, I.P., Parent-Massin, D., Binaglia, M., Steinkellner, H., Alexander, J., 2018. Appropriateness to set a group health-based guidance value for fumonisins and their modified forms. EFSA J. 16. https://doi.org/10.2903/j.efsa.2018.5172

Gelineau-van Waes, J., Rainey, M.A., Maddox, J.R., Voss, K.A., Sachs, A.J., Gardner, N.M., Wilberding, J.D., Riley, R.T., 2012. Increased sphingoid base-1-phosphates and failure of neural tube closure after exposure to fumonisin or FTY720. Birth Defects Res. Part A - Clin. Mol. Teratol. 94, 790–803. https://doi.org/10.1002/bdra.23074

Riley, R.T., Merrill, A.H., 2019. Ceramide synthase inhibition by fumonisins: A perfect storm of perturbed sphingolipid metabolism, signaling, and disease. J. Lipid Res. 60, 1183–1189. https://doi.org/10.1194/jlr.S093815

Sassa, T., Hirayama, T., Kihara, A., 2016. Enzyme activities of the ceramide synthases CERS2-6 are regulated by phosphorylation in the C-terminal region. J. Biol. Chem. 291, 7477–7487. https://doi.org/10.1074/jbc.M115.695858

Stiban, J., Tidhar, R., Futerman, A.H., 2010. Ceramide synthases: Roles in cell physiology and signaling. Adv. Exp. Med. Biol. 688, 60–71. https://doi.org/10.1007/978-1-4419-6741-1_4

Tidhar, R., Futerman, A.H., 2013. The complexity of sphingolipid biosynthesis in the endoplasmic reticulum. Biochim. Biophys. Acta - Mol. Cell Res. 1833, 2511–2518. https://doi.org/10.1016/j.bbamcr.2013.04.010