Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible

The Journal of Clinical Investigation
J C Drapier, J B Hibbs

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.

References

Jul 15, 1977·Science·J B HibbsJ B Weinberg
Jan 1, 1985·Annual Review of Biochemistry·Y Hatefi
Jan 12, 1972·Nature: New Biology·J B HibbsJ S Remington
Jul 21, 1967·Biochemical and Biophysical Research Communications·B H Robinson, J B Chappell
Feb 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·T A KentE Münck
Nov 1, 1982·The Journal of Cell Biology·D L Granger, A L Lehninger
Jan 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·H BeinertA J Thomson
Aug 5, 1983·Science·P Reichard, A Ehrenberg
Apr 15, 1983·Archives of Biochemistry and Biophysics·H Beinert, A J Thomson
Sep 17, 1984·Biochemical and Biophysical Research Communications·J B HibbsZ Vavrin
Feb 1, 1980·The Journal of Clinical Investigation·D L GrangerJ B Hibbs

❮ Previous
Next ❯

Citations

Sep 1, 1992·Annals of Neurology·T M DawsonS H Snyder
Jul 1, 1996·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J C Drapier, C Bouton
Mar 1, 1996·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D M Evans, S H Ralston
May 1, 1989·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·T F Patterson, V T Andriole
Aug 1, 1992·Biological Trace Element Research·E D Weinberg
Sep 4, 2009·Archives of Pharmacal Research·Young-Joon SurhYoung-Nam Cha
Apr 29, 1996·European Journal of Pharmacology·U K Messmer, B Brüne
Jan 1, 1994·Life Sciences·B BrüneE G Lapetina
Sep 1, 1990·Parasitology Today·S L James, J B Hibbs
Mar 1, 1995·Blood Reviews·G J Kontoghiorghes, E D Weinberg
Dec 1, 1992·Comparative Biochemistry and Physiology. B, Comparative Biochemistry·A HrabákF Antoni
Sep 1, 1996·Clinics in Dermatology·S McSorleyF Y Liew
Jan 1, 1992·Free Radical Biology & Medicine·D W Reif
Jan 1, 1996·Free Radical Biology & Medicine·M B JuckettG M Vercellotti
Jan 1, 1994·Cellular Signalling·U K Messmer, B Brüne
Sep 1, 1991·Research in Immunology·M LepoivreG Lemaire
Nov 1, 1995·Research in Immunology·J B Mannick
Feb 11, 1991·Current Opinion in Immunology·C F Nathan, J B Hibbs
Feb 1, 1994·Current Opinion in Immunology·N R Bastian, J B Hibbs
Jan 1, 1995·Advances in Neuroimmunology·A FranchiniE Ottaviani
Mar 1, 1994·Trends in Cell Biology·K PantopoulosM W Hentze
Nov 30, 1988·Biochemical and Biophysical Research Communications·J B HibbsE M Rachlin
Oct 16, 2003·Journal of Theoretical Biology·Danuta Wlodek, Michael Gonzales
Oct 17, 2001·Developmental and Comparative Immunology·N F NeumannM Belosevic
Jun 6, 2003·Journal of Ethnopharmacology·A Sá-NunesJ M Sforcin
Apr 27, 1999·Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie·S MnaimnehP Vincendeau
Feb 14, 2002·Free Radical Biology & Medicine·Hidekazu Tsukamoto
Jan 22, 1998·Free Radical Biology & Medicine·J B WeinbergW Chamulitrat
Mar 30, 2002·Critical Reviews in Oncology/hematology·Juliana C Kwok, Des R Richardson
Nov 7, 1998·British Journal of Pharmacology·L LecanuM Plotkine
Jun 18, 2002·Journal of Neurochemistry·Benoît ChénaisJean-Claude Drapier

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.