Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells |
| |
| Affiliation: | 1. Internal Medicine and Centre for Hemochromatosis and Heredometabolic Liver Diseases, ERN-EuroBloodNet Center for Iron Disorders, Azienda Ospedaliero-Universitaria di Modena - Policlinico, Modena, Italy;2. Department of Medical and Surgical Sciences, Università degli Studi di Modena e Reggio Emilia, Modena, Italy;3. General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Policlinico di Milano, Milan, Italy;4. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy;5. Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca’ Granda Ospedale Policlinico di Milano, Milan, Italy;6. Center for Genome Research, Università degli Studi di Modena e Reggio Emilia, Modena, Italy;1. Department of Microbiology and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China;2. Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China;3. Department of Pharmacology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
