PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway
Ferroptosis plays a crucial role in the secondary pathophysiological damage to brain tissue surrounding hematomas after intracerebral hemorrhage (ICH). While platelet factor 4 (PF4) is known to promote regeneration following peripheral nerve injury, its role in brain tissue repair after cerebral he...
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-11-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/11283 |
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| author | Na Hu Guohong Zhang Liping An Wei Wang Ran An Yunfeng Li |
| author_facet | Na Hu Guohong Zhang Liping An Wei Wang Ran An Yunfeng Li |
| author_sort | Na Hu |
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Ferroptosis plays a crucial role in the secondary pathophysiological damage to brain tissue surrounding hematomas after intracerebral hemorrhage (ICH). While platelet factor 4 (PF4) is known to promote regeneration following peripheral nerve injury, its role in brain tissue repair after cerebral hemorrhage remains unclear. In this study, Hemin-induced PC12 cells were treated with various inhibitors and assessed for viability, oxidative stress, and ferroptosis using a combination of assays, including CCK-8 (Cell Counting Kit-8), EdU (5-Ethynyl-2’-deoxyuridine), flow cytometry, and immunofluorescence. ICH cells were also treated with recombinant PF4 (Rm-PF4) and a CXCR3 antagonist (AMG487) to investigate the mechanism by which Rm-PF4 influences Hemin-induced PC12 cell injury and inflammation. Subsequently, ICH mouse models were established via collagenase injection. Neurological function in these mice was evaluated using the Cylinder and Corner tests. Histopathological damage to brain tissue was analyzed through HE, TUNEL, and Nissl staining, as well as immunohistochemistry, to further explore the role of Rm-PF4 in controlling neuroinflammation in vivo. Results showed that Rm-PF4 inhibited Hemin-mediated ferroptosis-induced PC12 cell damage and inflammation by activating the CXCR3/AKT1/SLC7A11 signaling pathway. Blocking the CXCR3/AKT1/SLC7A11 pathway partially reversed PF4's protective effects on Hemin-induced PC12 cells.In ICH mice, pro-inflammatory marker CD16 (3rd day) and anti-inflammatory marker Arg1 (7th day) were significantly decreased and increased, respectively (p<0.05). IL-6, TNF-α, and IL-1β levels were down-regulated in brain tissues after Rm-PF4 injection, which was significantly reversed by AMG487. PF4 inhibits ferroptosis after ICH reduced PC12 cell damage and the inflammatory response via activating the CXCR3/AKT1/SLC7A11 pathway.
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| format | Article |
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| institution | OA Journals |
| issn | 2831-0896 2831-090X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
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| series | Biomolecules & Biomedicine |
| spelling | doaj-art-fb294aaac8b3429f94774a3390221ae82025-08-20T02:05:52ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-11-0110.17305/bb.2024.11283PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathwayNa Hu0Guohong Zhang1Liping An2Wei Wang3Ran An4Yunfeng Li5Department of Biochemistry and Biology, School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio- Cerebrovascular Disease, Shijiazhuang, Hebei Province, China Department of Biochemistry and Biology, School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio- Cerebrovascular Disease, Shijiazhuang, Hebei Province, ChinaDepartment of Biochemistry and Biology, School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio- Cerebrovascular Disease, Shijiazhuang, Hebei Province, ChinaDepartment of Biochemistry and Biology, School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio- Cerebrovascular Disease, Shijiazhuang, Hebei Province, ChinaDepartment of Biochemistry and Biology, School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio- Cerebrovascular Disease, Shijiazhuang, Hebei Province, ChinaDepartment of Biochemistry and Biology, School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio- Cerebrovascular Disease, Shijiazhuang, Hebei Province, China Ferroptosis plays a crucial role in the secondary pathophysiological damage to brain tissue surrounding hematomas after intracerebral hemorrhage (ICH). While platelet factor 4 (PF4) is known to promote regeneration following peripheral nerve injury, its role in brain tissue repair after cerebral hemorrhage remains unclear. In this study, Hemin-induced PC12 cells were treated with various inhibitors and assessed for viability, oxidative stress, and ferroptosis using a combination of assays, including CCK-8 (Cell Counting Kit-8), EdU (5-Ethynyl-2’-deoxyuridine), flow cytometry, and immunofluorescence. ICH cells were also treated with recombinant PF4 (Rm-PF4) and a CXCR3 antagonist (AMG487) to investigate the mechanism by which Rm-PF4 influences Hemin-induced PC12 cell injury and inflammation. Subsequently, ICH mouse models were established via collagenase injection. Neurological function in these mice was evaluated using the Cylinder and Corner tests. Histopathological damage to brain tissue was analyzed through HE, TUNEL, and Nissl staining, as well as immunohistochemistry, to further explore the role of Rm-PF4 in controlling neuroinflammation in vivo. Results showed that Rm-PF4 inhibited Hemin-mediated ferroptosis-induced PC12 cell damage and inflammation by activating the CXCR3/AKT1/SLC7A11 signaling pathway. Blocking the CXCR3/AKT1/SLC7A11 pathway partially reversed PF4's protective effects on Hemin-induced PC12 cells.In ICH mice, pro-inflammatory marker CD16 (3rd day) and anti-inflammatory marker Arg1 (7th day) were significantly decreased and increased, respectively (p<0.05). IL-6, TNF-α, and IL-1β levels were down-regulated in brain tissues after Rm-PF4 injection, which was significantly reversed by AMG487. PF4 inhibits ferroptosis after ICH reduced PC12 cell damage and the inflammatory response via activating the CXCR3/AKT1/SLC7A11 pathway. https://www.bjbms.org/ojs/index.php/bjbms/article/view/11283PF4intracerebral hemorrhageferroptosisCXCR3/AKT1/SLC7A11 pathwayinflammatory response |
| spellingShingle | Na Hu Guohong Zhang Liping An Wei Wang Ran An Yunfeng Li PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway Biomolecules & Biomedicine PF4 intracerebral hemorrhage ferroptosis CXCR3/AKT1/SLC7A11 pathway inflammatory response |
| title | PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway |
| title_full | PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway |
| title_fullStr | PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway |
| title_full_unstemmed | PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway |
| title_short | PF4 inhibits ferroptosis-mediated intracerebral hemorrhage through modulating the CXCR3/AKT1/SLC7A11 signaling pathway |
| title_sort | pf4 inhibits ferroptosis mediated intracerebral hemorrhage through modulating the cxcr3 akt1 slc7a11 signaling pathway |
| topic | PF4 intracerebral hemorrhage ferroptosis CXCR3/AKT1/SLC7A11 pathway inflammatory response |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/11283 |
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