Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells.
We reported recently that moderate hypoxia and hypoxia-mimetic agents could induce growth arrest and differentiation of leukemic cells via the mediation of hypoxia-inducible factor 1 alpha (HIF-1alpha), but the exact molecular mechanisms remain largely unknown. In this study, human acute promonocytic leukemic U937 cells were incubated under 2% O2 or in 50 microM of the hypoxia mimetic agent cobalt chloride (CoCl2) and normal oxygen for 24 h, and their protein expression profiles were compared by 2-DE coupled with MALDI-TOF/TOF MS/MS. We identified 62 and 16 proteins that were significantly deregulated by hypoxia and CoCl2 treatment, respectively. These proteins were mainly involved in metabolism, gene expression regulation, signal transduction, cell proliferation, differentiation and apoptosis. As an example, N-myc downstream regulated gene 1 (NDRG1), a putative differentiation-related gene, was up-regulated in both 2% O2- and CoCl2-treated U937 cells. Moreover, enforced HIF-1alpha expression also elevated NDRG1 mRNA and protein in U937 cells. These data will provide some clues for understanding mechanisms by which leukemic cells response to hypoxia.
Han
Yu-Hui
YH
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, P. R. China.
Xia
Li
L
Song
Li-Ping
LP
Zheng
Ying
Y
Chen
Wen-Li
WL
Zhang
Lei
L
Huang
Ying
Y
Chen
Guo-Qiang
GQ
Wang
Li-Shun
LS
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020543:Proteome; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020298:U937 Cells
D020543:Proteome; D003035:Cobalt; C018021:cobaltous chloride