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Author Xu, Qin-Qin ♦ Xiao, Feng-Jun ♦ Sun, Hui-Yan ♦ Shi, Xue-Feng ♦ Wang, Hua ♦ Yang, Yue-Feng ♦ Li, Yu-Xiang ♦ Wang, Li-Sheng ♦ Ge, Ri-Li
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANIMAL CELLS ♦ ANIMALS ♦ ANOXIA ♦ APOPTOSIS ♦ CELL PROLIFERATION ♦ GLUCOSE ♦ INHIBITION ♦ METABOLISM ♦ MITOCHONDRIA ♦ MOLECULES ♦ OXIDATION ♦ PLANT GROWTH
Abstract Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction. - Highlights: • Hypoxia induces upregulation of HIF-1α, HIF-2α and Ptpmt1; HIF-2a induces Ptpmt1 upregulation in TF-1 cells. • PTPMT-1 inhibition reduces growth and induces apoptosis of TF-1 cells. • PTPMT1 inhibition downregulates Glut-1, Glut-3 expression and reduces glucose consumption.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-03-18
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 471
Issue Number 4


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