title: Ptpmt1 induced by HIF-2α regulates the proliferation and glucose metabolism in erythroleukemia cells.
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.
authors.affiliation: High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001, PR China; Qinghai Provincial People's Hospital, Xining, PR China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Xu
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, PR China.
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Xiao
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, PR China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Sun
authors.affiliation: High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001, PR China; Qinghai Provincial People's Hospital, Xining, PR China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Shi
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, PR China.
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, PR China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850, PR China. Electronic address: wangls@bmi.ac.cn.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
authors.affiliation: High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001, PR China. Electronic address: geriligao@hotmail.com.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1; D017027:Protein Tyrosine Phosphatases
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005947:Glucose; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051059:PTEN Phosphohydrolase; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C495687:SLC2A3 protein, human; C000612027:Ptpmt1 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: Erythroleukemia; HIF-2α; Hypoxia; Ptpmt1