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Article Publish Status: FREE
Abstract Title:

Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I.

Abstract Source:

Cell Death Dis. 2023 Jan 21 ;14(1):50. Epub 2023 Jan 21. PMID: 36681688

Abstract Author(s):

Hao Wu, Ying Li, Qian Zhang, Hanxun Wang, Wenyu Xiu, Pu Xu, Yujie Deng, Wanxu Huang, Dan Ohtan Wang

Article Affiliation:

Hao Wu

Abstract:

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, 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.

Study Type : In Vitro Study

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