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Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells.
Cell Signal. 2020 Aug; 72:109633.CS

Abstract

Ferroptosis is a regulated form of cell death characterized by the iron-dependent accumulation of lipid hydroperoxides. Ceruloplasmin (CP) is a glycoprotein that plays an essential role in iron homeostasis. However, whether CP regulates ferroptosis has not been reported. Here, we show that CP suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma (HCC) cells. Depletion of CP promoted erastin- and RSL3-induced ferroptotic cell death and resulted in the accumulation of intracellular ferrous iron (Fe2+) and lipid reactive oxygen species (ROS). Moreover, overexpression of CP suppressed erastin- and RSL3-induced ferroptosis in HCC cells. In addition, a novel frameshift mutation (c.1192-1196del, p.leu398serfs) of CP gene newly identified in patients with iron accumulation and neurodegenerative diseases lost its ability to regulate iron homeostasis and thus failed to participate in the regulation of ferroptosis. Collectively, these data suggest that CP plays an indispensable role in ferroptosis by regulating iron metabolism and indicate a potential therapeutic approach for hepatocellular carcinoma.

Authors+Show Affiliations

School of Life Science, Beijing Institute of Technology, Beijing 100081, China; The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.School of Life Science, Beijing Institute of Technology, Beijing 100081, China.School of Life Science, Beijing Institute of Technology, Beijing 100081, China.The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address: yangyf@bit.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32283255

Citation

Shang, Yuxue, et al. "Ceruloplasmin Suppresses Ferroptosis By Regulating Iron Homeostasis in Hepatocellular Carcinoma Cells." Cellular Signalling, vol. 72, 2020, p. 109633.
Shang Y, Luo M, Yao F, et al. Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell Signal. 2020;72:109633.
Shang, Y., Luo, M., Yao, F., Wang, S., Yuan, Z., & Yang, Y. (2020). Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cellular Signalling, 72, 109633. https://doi.org/10.1016/j.cellsig.2020.109633
Shang Y, et al. Ceruloplasmin Suppresses Ferroptosis By Regulating Iron Homeostasis in Hepatocellular Carcinoma Cells. Cell Signal. 2020;72:109633. PubMed PMID: 32283255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. AU - Shang,Yuxue, AU - Luo,Meiying, AU - Yao,Fengping, AU - Wang,Shukun, AU - Yuan,Zengqiang, AU - Yang,Yongfei, Y1 - 2020/04/10/ PY - 2020/02/12/received PY - 2020/04/08/revised PY - 2020/04/08/accepted PY - 2020/4/14/pubmed PY - 2020/4/14/medline PY - 2020/4/14/entrez KW - Ceruloplasmin KW - Ferroptosis KW - Hepatocellular carcinoma KW - Iron homeostasis KW - Lipid ROS SP - 109633 EP - 109633 JF - Cellular signalling JO - Cell. Signal. VL - 72 N2 - Ferroptosis is a regulated form of cell death characterized by the iron-dependent accumulation of lipid hydroperoxides. Ceruloplasmin (CP) is a glycoprotein that plays an essential role in iron homeostasis. However, whether CP regulates ferroptosis has not been reported. Here, we show that CP suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma (HCC) cells. Depletion of CP promoted erastin- and RSL3-induced ferroptotic cell death and resulted in the accumulation of intracellular ferrous iron (Fe2+) and lipid reactive oxygen species (ROS). Moreover, overexpression of CP suppressed erastin- and RSL3-induced ferroptosis in HCC cells. In addition, a novel frameshift mutation (c.1192-1196del, p.leu398serfs) of CP gene newly identified in patients with iron accumulation and neurodegenerative diseases lost its ability to regulate iron homeostasis and thus failed to participate in the regulation of ferroptosis. Collectively, these data suggest that CP plays an indispensable role in ferroptosis by regulating iron metabolism and indicate a potential therapeutic approach for hepatocellular carcinoma. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/32283255/Ceruloplasmin_suppresses_ferroptosis_by_regulating_iron_homeostasis_in_hepatocellular_carcinoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(20)30110-8 DB - PRIME DP - Unbound Medicine ER -
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