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Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible.
J Clin Invest. 1986 Sep; 78(3):790-7.JCI

Abstract

Previous studies show that cytotoxic activated macrophages cause inhibition of DNA synthesis, inhibition of mitochondrial respiration, and loss of intracellular iron from tumor cells. Here we examine aconitase, a citric acid cycle enzyme with a catalytically active iron-sulfur cluster, to determine if iron-sulfur clusters are targets for activated macrophage-induced iron removal. Results show that aconitase activity declines dramatically in target cells after 4 h of co-cultivation with activated macrophages. Aconitase inhibition occurs simultaneously with arrest of DNA synthesis, another early activated macrophage-induced metabolic change in target cells. Dithionite partially prevents activated macrophage induced aconitase inhibition. Furthermore, incubation of injured target cells in medium supplemented with ferrous ion plus a reducing agent causes near-complete reconstitution of aconitase activity. The results show that removal of a labile iron atom from the [4Fe-4S] cluster, by a cytotoxic activated macrophage-mediated mechanism, is causally related to aconitase inhibition.

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PMC Free PDF

Authors

Drapier JC
No affiliation info available
Hibbs JB
No affiliation info available

MeSH

Aconitate HydrataseAnimalsCell LineCitratesCitric AcidDNADithioniteFemaleFerrous CompoundsIronIron-Sulfur ProteinsIsocitrate DehydrogenaseKineticsLipopolysaccharidesMacrophage ActivationMacrophagesMaleMetalloproteinsMiceMice, Inbred C3HNeoplasms, ExperimentalOxygen ConsumptionSpectrophotometry

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3745439

Citation

Drapier, J C., and J B. Hibbs. "Murine Cytotoxic Activated Macrophages Inhibit Aconitase in Tumor Cells. Inhibition Involves the Iron-sulfur Prosthetic Group and Is Reversible." The Journal of Clinical Investigation, vol. 78, no. 3, 1986, pp. 790-7.
Drapier JC, Hibbs JB. Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. J Clin Invest. 1986;78(3):790-7.
Drapier, J. C., & Hibbs, J. B. (1986). Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. The Journal of Clinical Investigation, 78(3), 790-7.
Drapier JC, Hibbs JB. Murine Cytotoxic Activated Macrophages Inhibit Aconitase in Tumor Cells. Inhibition Involves the Iron-sulfur Prosthetic Group and Is Reversible. J Clin Invest. 1986;78(3):790-7. PubMed PMID: 3745439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. AU - Drapier,J C, AU - Hibbs,J B,Jr PY - 1986/9/1/pubmed PY - 2001/3/28/medline PY - 1986/9/1/entrez SP - 790 EP - 7 JF - The Journal of clinical investigation JO - J Clin Invest VL - 78 IS - 3 N2 - Previous studies show that cytotoxic activated macrophages cause inhibition of DNA synthesis, inhibition of mitochondrial respiration, and loss of intracellular iron from tumor cells. Here we examine aconitase, a citric acid cycle enzyme with a catalytically active iron-sulfur cluster, to determine if iron-sulfur clusters are targets for activated macrophage-induced iron removal. Results show that aconitase activity declines dramatically in target cells after 4 h of co-cultivation with activated macrophages. Aconitase inhibition occurs simultaneously with arrest of DNA synthesis, another early activated macrophage-induced metabolic change in target cells. Dithionite partially prevents activated macrophage induced aconitase inhibition. Furthermore, incubation of injured target cells in medium supplemented with ferrous ion plus a reducing agent causes near-complete reconstitution of aconitase activity. The results show that removal of a labile iron atom from the [4Fe-4S] cluster, by a cytotoxic activated macrophage-mediated mechanism, is causally related to aconitase inhibition. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/3745439/Murine_cytotoxic_activated_macrophages_inhibit_aconitase_in_tumor_cells__Inhibition_involves_the_iron_sulfur_prosthetic_group_and_is_reversible_ DB - PRIME DP - Unbound Medicine ER -