Authors: M Guo LP Song Y Jiang W Liu Y Yu GQ Chen
Publish Date: 2006/01/13
Volume: 11, Issue: 1, Pages: 67-77
Abstract
Hypoxia presents proapoptotic and antiapoptotic biphasic effects that appear to be dependent upon cell types and conditions around cells The substantial reports demonstrated that commonly used hypoxiamimetic agents cobalt chloride CoCl2 and desferrioxamine DFO could also induce apoptosis in many different kinds of cells but the mechanism was poorly understood In this work we compare the apoptosisinducing effects of these two hypoxiamimetic agents with acute myeloid leukemic cell lines NB4 and U937 as in vitro models The results show that both of them induce these leukemic cells to undergo apoptosis with a loss of mitochondrial transmembrane potentials ΔΨ m the activation of caspase3/8 and the cleavage of antiapoptotic protein Mcl1 together with the accumulation of hypoxiainducible factor1 alpha HIF1α protein a critical regulator for the cellular response to hypoxia Metavanadate and sodium nitroprusside significantly abrogate DFO rather than CoCl2induced mitochondrial Δ Ψ m collapse caspase3/8 activation Mcl1 cleavage and apoptosis but they fail to influence DFO and CoCl2induced HIF1α protein accumulation Moreover inducible expression of HIF1α gene dose not alter DFO and CoCl2induced apoptosis in U937 cells In conclusion these results propose that although both DFO and CoCl2induced leukemic cell apoptosis by mitochondrial pathwaydependent and HIF1αindependent mechanisms DFO and CoCl2induced apoptosis involves different initiating signal pathways that remain to be investigated
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