Erastin-induced ferroptosis is a regulator forthe growth and function of humanpancreatic islet-like cell clusters  

作　　者：Xing Yu Li Po Sing Leung 

机构地区：[1]School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Shatin,Hong Kong,China [2]Key Laboratory for Regenerative Medicine,Ministry of Education,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong,China

出　　处：《Cell Regeneration》2020年第1期171-179,共9页细胞再生（英文）

基　　金：This research was supported by the General Research Fund of The Research Grants Council of Hong Kong(Ref.#14107415);The Chinese University of Hong Kong(Ref.#CUHK7104280)to PS Leung.

摘　　要：Ferroptosis is a newly identified and novel form of cell death, which is characterized by an iron- and reactiveoxygen species (ROS)-dependent manner. Potential utility of ferroptotic cell death has been recently proposed forcancer treatment. Meanwhile, ROS generation and apoptosis are inherently consequent to cell apoptosis anddysfunction during islet cell preparation and transplantation. Whether ferroptosis induction is a regulator for cellviability and function in human pancreatic islet-cell clusters (ICCs) derived from pancreatic progenitor cells (PPCs)remains elusive. We thus sought to induce ferroptosis in our established cell culture system of human PPCs/ICCs,examine the effects of ferroptosis on ICCs, and explore the potential regulatory pathways involved. Our resultsshowed that ICCs were prone to the use of ferroptosis-inducing and inhibiting agents under our culture conditions.Erastin, a ferroptosis inducer, was found to trigger ferroptosis in ICCs, without the apparent detection of other typesof cell death involved, such as apoptosis and autophagy. In corroboration, the use of ferroptosis inhibitor,ferrostatin-1 (Fer-1), was found to enhance the cell viability of ICCs and prevent them from ferroptosis as well asimprove its function. Mechanistically, the erastin-induced ferroptosis in ICCs was probably mediated via activation ofJNK/P38/MAPK pathways and upregulation of NOX4 expression. Together, our findings may provide a scientificbasis of ferroptosis inhibition as a potential for the amelioration of ICC survival and functionality during islettransplantation in diabetic patients.

关 键 词：Apoptosis Autophagy Cell death Erastin Ferrostatin-1 ISLETS NOX4 P38 

分 类 号：R73[医药卫生—肿瘤]