EFFECT OF 6-HYDROXYDOPAMINE ON MURINE HEMATOPOIETIC STEM-CELLS - ENHANCED CYTOTOXICITY ON MEGAKARYOCYTE COLONY-FORMING-UNITS

被引:7
作者
GORDON, BG [1 ]
DEBOER, JM [1 ]
WOOLDRIDGE, LD [1 ]
SHARP, JG [1 ]
机构
[1] UNIV NEBRASKA,MED CTR,DEPT ANAT,OMAHA,NE 68105
关键词
D O I
10.1016/0024-3205(91)90025-7
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We examined the effect of catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) on murine committed megakaryocyte progenitor cells, the megakaryocyte-colony forming unit (CFU-Meg). More mature cells of the megakaryocyte series have the capacity for active uptake of catecholamines, and we speculated that the CFU-Meg would also take up 6-OHDA and be selectively killed. CFU-Meg were much more sensitive to the effects of this agent than were granulocyte-macrophage colony forming units (CFU-GM) or spleen-colony forming units. Co-incubation with catalase, which would destroy hydrogen peroxide generated extracellularly by the autoxidation of 6-OHDA, ablated 6-OHDA toxicity towards CFU-GM, but also significantly reduced the effect on CFU-Meg. Mazindol, a selective dopamine uptake inhibitor did not alter 6-OHDA effect on either CFU-Meg or CFU-GM. Finally, CFU-Meg were no more sensitive to incubation with hydrogen peroxide than were CFU-GM. These data suggest that CFU-Meg, unlike their more mature progeny, do not actively concentrate 6-OHDA, and the excess toxicity of this agnet towards CFU-Meg is probably due to increased sensitivity to autoxidation products of 6-OHDA, other than hydrogen peroxide, generated extracellularly.
引用
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页码:121 / 127
页数:7
相关论文
共 23 条
[1]  
ABRAMS WB, 1969, CLIN PHARMACOL THER, V10, P702
[2]  
BRALLEY TR, 1978, J CELL PHYSL, V97, P517
[3]  
BRICKER LJ, 1984, EXP HEMATOL, V12, P672
[4]   THE ROLE OF REACTIVE OXYGEN COMPOUNDS DERIVED FROM 6-HYDROXYDOPAMINE FOR BONE-MARROW PURGING FROM NEURO-BLASTOMA CELLS [J].
BRUCHELT, G ;
BUCK, J ;
GIRGERT, R ;
TREUNER, J ;
NIETHAMMER, D .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 130 (01) :168-174
[5]   UPTAKE OF H-3 DOPAMINE IN MEGAKARYOCYTES AND BLOOD-PLATELETS MEASURED BY QUANTITATIVE ELECTRON-MICROSCOPE AUTORADIOGRAPHY [J].
DAIMON, T ;
DAVID, H .
HISTOCHEMISTRY, 1986, 85 (06) :453-456
[6]  
GEWIRTZ AM, 1986, SEMIN HEMATOL, V23, P27
[7]  
HEIKKILA R, 1972, MOL PHARMACOL, V8, P241
[8]   EVIDENCE FOR DEGENERATION OF SYMPATHETIC-NERVE TERMINALS CAUSED BY ORTHO-QUINONES AND PARA-QUINONES OF 6-HYDROXYDOPAMINE [J].
HEIKKILA, RE ;
MYTILINEOU, C ;
COTE, L ;
COHEN, G .
JOURNAL OF NEUROCHEMISTRY, 1973, 20 (05) :1345-+
[9]  
HEIKKILA RE, 1977, EUR J PHARMACOL, V45, P32
[10]   CHOLINESTERASE AS A POSSIBLE MARKER FOR EARLY CELLS OF MEGAKARYOCYTIC SERIES [J].
JACKSON, CW .
BLOOD, 1973, 42 (03) :413-421