title: [Effect of PD98059 on Proliferation and Apoptosis of CD71(+),CD235a(+) Nucleated Erythrocytes in the Patients with High Altitude Polycythemia].
abstract: Objective： To study the effect of PD98059, a specific inhibitor of Ras/Raf/MEK/ERK signaling pathway, on the proliferation and apoptisis of bone marrow CD71(+), CD235a(+) nucleated erythrocytes in patients with high altitude polycythemia (HAPC) and the pathogenesis of HAPC.
  
  
  METHODS
  The CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients and controls (patients with simple obsolete stracture) were sorted by using the immunemagnetic beads, then were added with 5, 10, 20 µmol/L of PD98059 and DMSO (as control) and were cultured for 72 h under hypoxia. The cell apoptosis was detected by flow cytometry with Annexin V and PI double staining, the cell proliferation was detected by CCK8 method, at same time the erythroid colong-formation ability of bone marrow mononuclear cells (BMMNC) treated with 5, 10, 20 µmol/L of PD98059 and DMSO was observed.
  
  
  RESULTS
  With the increase of PD98059 concentration, the apoptosis rate of bone marrow CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients was enhanced (r=0.807,P<0.01), while the proliferation rate of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients dereased (r=0.502,P<0.01). The erythroid colong-formation ability of BMMNC in HAPC patients decreased with the increase of PD98059 concentration (r=0.504,P<0.01). There were statistic differences among different groups at 7 and 14 d.
  
  
  CONCLUSIONS
  The MEK specific inhibitor PD98059 can inhibit the proliferation and promote the apoptosis of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients, then inhibit the excessive accumulation of erythrocytes.
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Feng
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.E-mail:13997244508@163.com.
authors.forename: Lin-Hua
authors.initials: LH
authors.lastname: Ji
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Yuan-Fang
authors.initials: YF
authors.lastname: Han
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ren
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Li
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Hematology, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Cui
mesh_terms: D000532:Altitude Sickness; D017209:Apoptosis; D001853:Bone Marrow; D001854:Bone Marrow Cells; D049109:Cell Proliferation; D004900:Erythroblasts; D004906:Erythrocyte Count; D004912:Erythrocytes; D005419:Flavonoids; D005434:Flow Cytometry; D006021:Glycophorins; D006801:Humans
chemical_list: D005419:Flavonoids; D006021:Glycophorins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one