A chemical-genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase.
Nat Chem Biol
; 15(2): 169-178, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30643283
ABSTRACT
Reactive oxygen species (ROS) are transient, highly reactive intermediates or byproducts produced during oxygen metabolism. However, when innate mechanisms are unable to cope with sequestration of surplus ROS, oxidative stress results, in which excess ROS damage biomolecules. Oxidized phosphatidylserine (PS), a proapoptotic 'eat me' signal, is produced in response to elevated ROS, yet little is known regarding its chemical composition and metabolism. Here, we report a small molecule that generates ROS in different mammalian cells. We used this molecule to detect, characterize and study oxidized PS in mammalian cells. We developed a chemical-genetic screen to identify enzymes that regulate oxidized PS in mammalian cells and found that the lipase ABHD12 hydrolyzes oxidized PS. We validated these findings in different physiological settings including primary peritoneal macrophages and brains from Abhd12-/- mice under inflammatory stress, and in the process, we functionally annotated an enzyme regulating oxidized PS in vivo.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilserinas
/
Monoacilglicerol Lipases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Chem Biol
Assunto da revista:
BIOLOGIA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia