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The dual role of FSP1 in programmed cell death: resisting ferroptosis in the cell membrane and promoting necroptosis in the nucleus of THP-1 cells.
Tan, Xiaoqian; He, Yinling; Yu, Panpan; Deng, Yunong; Xie, Zhongcheng; Guo, Jiami; Hou, Qin; Li, Pin; Lin, Xiaoyan; Ouyang, Siyu; Ma, Wentao; Xie, Yushu; Guo, Zilong; Chen, Dandan; Zhang, Zhixia; Zhu, Yunyu; Huang, Fei; Zhao, Ziye; Zhang, Cen; Guo, Zhirong; Chen, Xi; Peng, Tianhong; Li, Liang; Xie, Wei.
Afiliación
  • Tan X; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • He Y; School of Basic Medical Sciences, Xiangnan University, Chenzhou, 423000, Hunan, China.
  • Yu P; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Deng Y; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Xie Z; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Guo J; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Hou Q; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Li P; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Lin X; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Ouyang S; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Ma W; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Xie Y; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Guo Z; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Chen D; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Zhang Z; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Zhu Y; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Huang F; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Zhao Z; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Zhang C; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Guo Z; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Chen X; Class of Clinical Medicine, University of South China, Hengyang, 421001, Hunan, China.
  • Peng T; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Li L; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. 2602406228@qq.com.
  • Xie W; Department of Physiology, Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. 26002860@qq.com.
Mol Med ; 30(1): 102, 2024 Jul 15.
Article en En | MEDLINE | ID: mdl-39009982
ABSTRACT

BACKGROUND:

Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear.

METHODS:

THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot.

RESULTS:

The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis.

CONCLUSION:

We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ferroptosis / Necroptosis Límite: Humans Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ferroptosis / Necroptosis Límite: Humans Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido