Uptake of hematin and growth of malignant murine erythroleukemia cells depleted of endogenous heme by succinylacetone.
Heme levels and growth of malignant murine erythroleukemia cells in heme-free medium are drastically reduced by incubation of these cells in the presence of 4,6-dioxoheptanoic acid [succinylacetone (SA)]. When hematin was added to the culture medium of heme-depleted cells, the intracellular heme levels returned to normal, and growth inhibition produced by SA was also reversed. However, when cells depleted of heme by growth in heme-free medium containing SA were placed in heme-free medium without SA, heme levels were restored to normal, and growth was resumed. Hematin uptake in both untreated and heme-depleted malignant murine erythroleukemia cells exhibited biphasic kinetics, with a rapid phase of about 2 min followed by a slower uptake. The rate of uptake of exogenous hematin was slightly greater at 37 degrees than at 20 degrees. Although supplementation of heme-free medium with exogenous hematin increased total cellular heme in both untreated and heme-depleted malignant murine erythroleukemia cells, the fraction of heme in the 20,000 X g sediment was unaffected. A nonmalignant fibroblastic cell line, 3T3, exhibited little or no capacity to take up exogenous hematin.
D000624:5-Aminolevulinate Synthetase / Q000037:antagonists & inhibitors; D000818:Animals; D001692:Biological Transport; D002455:Cell Division; D006418:Heme / Q000031:analogs & derivatives* / Q000172:deficiency; D006427:Hemin / Q000378:metabolism*; D006537:Heptanoates / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D007651:Keto Acids / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D007942:Leukemia, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013696:Temperature
D006537:Heptanoates; D006538:Heptanoic Acids; D007651:Keto Acids; D006418:Heme; C020804:succinylacetone; D006427:Hemin; D000624:5-Aminolevulinate Synthetase