Effect of 6-hydroxydopamine on murine hematopoietic stem cells: Enhanced cytotoxicity on megakaryocyte colony forming units

Bruce Geoffrey Gordon, Joanne M. DeBoer, Leslee D. Wooldridge, John G Sharp

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 agent towards CFU-Meg is probably due to increased sensitivity to autoxidation products of 6-OHDA, other than hydrogen peroxide, generated extracellularly.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalLife Sciences
Volume49
Issue number2
DOIs
StatePublished - 1991

Fingerprint

Megakaryocytes
Oxidopamine
Cytotoxicity
Hematopoietic Stem Cells
Stem cells
Stem Cells
Granulocyte-Macrophage Progenitor Cells
Hydrogen Peroxide
Toxicity
Mazindol
Megakaryocyte Progenitor Cells
Dopamine Uptake Inhibitors
Macrophages
Neurotoxins
Catalase
Catecholamines
Spleen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effect of 6-hydroxydopamine on murine hematopoietic stem cells : Enhanced cytotoxicity on megakaryocyte colony forming units. / Gordon, Bruce Geoffrey; DeBoer, Joanne M.; Wooldridge, Leslee D.; Sharp, John G.

In: Life Sciences, Vol. 49, No. 2, 1991, p. 121-127.

Research output: Contribution to journalArticle

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