Inhibition of iron uptake in HL60 cells by 2-formylpyridine monothiosemicarbazonato Cu(II). Arch Biochem Biophys 1991 Sep;289(2):393-8
Date
09/01/1991Pubmed ID
1654860DOI
10.1016/0003-9861(91)90429-mScopus ID
2-s2.0-0026047967 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
The electron paramagnetic resonance (EPR) signal of the tyrosyl radical attributed to ribonucleoside diphosphate reductase decreases after treatment of promyelocytic leukemic HL60 cells with 2-formylpyridine thiosemicarbazonato copper(II) (CuL). According to EPR studies, CuL forms adducts with both histidine and cysteine-like Lewis bases associated with isolated membranes from HL60 cells. After the addition of CuL, the EPR signal for the cysteine-like adduct decreases substantially over a 15-min period. The reduction of signal is consistent with oxidation of thiols as shown by an analysis of sulfhydryl content. It is hypothesized that receptor-mediated transferrin internalization is inhibited by oxidation of critical thiols. Since the uptake of 59Fe-transferrin is greatly inhibited by the treatment of HL60 cells with CuL, the reduced uptake of iron by cells, in the presence of CuL, may lead to decreased iron availability for the activity of the M2 subunit of ribonucleotide reductase and a subsequent decrease in the tyrosyl radical signal of the enzyme. Moreover, the intact subunit M2 is no longer detected by EPR, even after the addition of excess iron.
Author List
Narasimhan J, Antholine WE, Chitambar CR, Petering DHMESH terms used to index this publication - Major topics in bold
Biological Transport, ActiveElectron Spin Resonance Spectroscopy
Free Radicals
Humans
Iron
Organometallic Compounds
Oxidation-Reduction
Ribonucleoside Diphosphate Reductase
Sulfhydryl Compounds
Transferrin
Tumor Cells, Cultured
Tyrosine