(Press-News.org) https://doi.org/10.1016/j.apsb.2025.10.027
This new article publication from Acta Pharmaceutica Sinica B, discusses how palmitoylation of Tfr1 enhances platelet ferroptosis and liver injury in heat stroke.
Heat stroke (HS) is a severe medical emergency characterized by coagulation and high mortality due to organ injury. This study identifies a novel mechanism in which platelet ferroptosis, driven by transferrin receptor 1 (Tfr1) palmitoylation, significantly contributes to liver injury in HS. The findings reveal a strong inverse correlation between platelet count and organ damage, especially liver injury, as well as mortality rates. Using murine models, it was demonstrated that inhibiting Tfr1-mediated ferroptosis in platelets mitigates thrombocytopenia and decreases Interleukin-1β (IL-1β) secretion, thereby improving liver function and survival outcomes. This research highlights Tfr1 palmitoylation as a critical factor in iron transport within platelets, with the palmitoylation inhibitor 2-bromopalmitate (2BP) effectively reducing total iron, Fe2+, lipid ROS, 4-hydroxynonenal (4-HNE), and cell cytotoxicity under heat stress. These results suggest that targeting Tfr1 palmitoylation-dependent ferroptosis in platelets offers a novel therapeutic strategy for treating HS-induced thrombocytopenia and liver injury.
Keywords: Heat stroke, Heat stroke-induced liver injury, Platelet, Ferroptosis, Tfr1, Palmitoylation, Cytokines, IL-1β
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525007051-ga1_lrg.jpg
Tfr1 palmitoylation-mediated ferroptosis in platelets, accompanied by IL-1β secretion, exacerbates liver injury in HS. The findings provide novel insights into thrombocytopenia and liver injury in HS, offering a potential therapeutic strategy to mitigate HS-induced thrombocytopenia, liver injury, and poor prognosis.
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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.
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CiteScore: 24.3
Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.8
ISSN 2211-3835
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Qiyuan An, Riqing Wei, Zhicheng Huang, Youyong Tang, Minghao Wang, Sixiao He, Kaihua Huang, Zhifeng Liu, Meimei Zhang, Ru Li, Junhao Huang, Keying Zhang, Jingjing Ji, Liwei Xie, Qiang Ma, Palmitoylation of Tfr1 enhances platelet ferroptosis and liver injury in heat stroke, Acta Pharmaceutica Sinica B, Volume 16, Issue 1, 2026, Pages 270-286, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.10.027
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https://doi.org/10.1016/j.apsb.2025.10.028
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