Elucidation of induction of ferroptosis and inhibition of tumor growth caused by suppressing cystine transporter xCT

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H06648
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Yamagata University
• Principal Investigator: Kobayashi Sho 山形大学, 大学院医学系研究科, 助教 (10779490)
• Research Collaborator: Fujii Junichi 山形大学, 大学院医学系研究科, 教授 (00222258) ; Homma Takujiro 山形大学, 大学院医学系研究科, 助教 (70743566)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Keywords: グルタチオン / システイン / xCT / ferroptosis / マクロファージ / オフタルミン酸

Outline of Final Research Achievements

We established a method for simultaneous measurement of low molecular thiols and ophthalmic acid, which is an oxidative stress marker, and found an increase in ophthalmic acid level but a decrease in glutathione level in plasma and liver of fasting mice. Analyses of macrophages from xCT-deficient mice by using this method indicated that they were severe deficiency in cysteine and glutathione but could survive for several days under conditions with high oxidative stress. These results suggest that macrophages have unique glutathione-independent survival system. Meantime, nitric oxide production in xCT-deficient macrophages was significantly decreased compared to that in WT cells.

Free Research Field

生化学