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ZDHHC12-dependent Nrf2 palmitoylation mediates the anti-ferroptotic and anti-inflammatory effects of artemisinin in mastitis
Fan Zeqiu, Luo Yang, Zhang Zhenzhao, Cheng Feng, Yi Kangle, Liu Wenjun
Journal:Communications Biology
IF:5.8
DOI:10.1038/s42003-026-10677-z
PMID:
Published:2026-07-16
research field:神经科学分子生物学基因治疗合成生物学生物医学工程干细胞生物学病毒学
Abstract
Artemisinin (ART) is known to alleviate inflammation in mastitis, but its effect on ferroptosis in mammary epithelial cells and the associated regulatory mechanisms has not been fully clarified. Here, we demonstrate that ART markedly attenuates inflammatory injury and ferroptosis in Staphylococcus aureus -induced mastitis models both in vivo and in vitro. ART treatment reduces iron accumulation and lipid peroxidation while restoring antioxidant capacity, accompanied by improved mitochondrial integrity. Mechanistically, ART upregulates the palmitoyltransferase ZDHHC12, which promotes palmitoylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and facilitates its nuclear translocation. Activation of Nrf2 subsequently enhances heme oxygenase-1 (HO-1) signaling, leading to suppression of inflammation and ferroptosis. Collectively, these findings reveal that ART exerts protective effects against mastitis by activating the ZDHHC12/Nrf2/HO‑1 axis, highlighting ART as a potential therapeutic agent for mastitis through coordinated inhibition of inflammation and ferroptosis.
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