Wu H, Li Y, Zhang Q, Wang H, Xiu W, Xu P, Deng Y, Huang W, Wang DO

Parthanatos is one of the major pathways of programmed cell death in ischemic stroke characterized by DNA damage, poly (ADP-ribose) polymerases (PARP) activation, and poly (ADP-ribose) (PAR) formation. Here we demonstrate that crocetin, a natural potent antioxidant compound from Crocus sativus, antagonizes parthanatos in ischemic stroke. We reveal that mechanistically, ...

Read More

crocetin inhibits NADPH oxidase 2 (NOX2) activation to reduce reactive oxygen species (ROS) and PAR production at the early stage of parthanatos. Meanwhile we demonstrate that PARylated hexokinase-I (HK-I) is a novel substrate of E3 ligase RNF146 and that crocetin interacts with HK-I to suppress RNF146-mediated HK-I degradation at the later stage of parthanatos, preventing mitochondrial dysfunction and DNA damage that ultimately trigger the irreversible cell death. Our study supports further development of crocetin as a potential drug candidate for preventing and/or treating ischemic stroke.

Date: Jan. 21, 2023

View in: Pubmed Google Scholar

245069