Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence

Therapy‐induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro‐...

Full description

Saved in:
Bibliographic Details
Published inProteomics (Weinheim) Vol. 20; no. 10; pp. e2000013 - n/a
Main Authors Millner, Alec, Lizardo, Darleny Y., Atilla‐Gokcumen, Gunes Ekin
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 01.05.2020
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Therapy‐induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro‐survival activity, it is envisioned in this article that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, a tissue culture model system is established and the cellular lipidomes of senescent and proliferating cells are comparatively analyzed. Out of thousands of features detected, 17 species are identified that show significant changes in senescent cells. The majority of these species (11 out of 17) are atypical sphingolipids, 1‐deoxyceramides/dihydroceramides, which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids are depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide result in decreased senescence, suggesting that these species might play a key role in this process.
Bibliography:Present address: Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1615-9853
1615-9861
DOI:10.1002/pmic.202000013