Tl⁺ Showed Negligible Interaction with Inner Membrane Sulfhydryl Groups of Rat Liver Mitochondria, but Formed Complexes with Matrix Proteins

Abstract

The effects of Tl(+) on protein sulfhydryl (SH) groups, swelling, and respiration of rat liver mitochondria (RLM) were studied in a medium containing TlNO3 and sucrose, or TlNO3 and KNO3 as well as glutamate plus malate, or succinate plus rotenone. Detected with Ellman's reagent, an increase in the content of the SH groups was found in the inner membrane fraction, and a simultaneous decline was found in the content of the matrix-soluble fraction for RLM, incubated and frozen in 25-75 mM TlNO3 . This increase was greater in the medium containing KNO3 regardless of the presence of Ca(2+) . It was eliminated completely for RLM injected in the medium containing TlNO3 and then washed and frozen in the medium containing KNO3 . Calcium-loaded RLM showed increased swelling and decreased respiration. These results suggest that a ligand interaction of Tl(+) with protein SH groups, regardless of the presence of calcium, may underlie the mechanism of thallium toxicity.

Influence of Tl(+) on the Ca(2+) and Na(+) movement across rat neonatal cardiomyocytes and rat heart mitochondria membranes

“…Some possible toxic mechanisms of Tl + can be the disturbance of calcium homeostasis, inhibition of cellular respiration, as well as ligand formation of Tl + with protein sulfhy dryl groups [1]. Our in vitro studies with RLM have revealed that Tl + was able to form complexes with mitochondrial proteins [35]. In our experiments, we observed that the inhibition of Ca 2+ influx with Ca 2+ free EGTA solution prevented the sustained/ transient increase in [Ca 2+ ] i induced by the addition of Tl + (Fig.…”

Y 3+ , La 3+ , and some bivalent metals inhibited the opening of the Tl + -induced permeability transition pore in Ca 2+ -loaded rat liver mitochondria

“…In other words, the Tl + -induced MPTP opening can occur only in experiments with Ca 2+ -preloaded mitochondria. Unlike Tl + , bivalent heavy metal ions (Cd 2+ , Hg 2+ , Pb 2+ , and Zn 2+ ) and Ag + possess high affinity to molecular SH groups and can stimulate the MPTP opening in media free of Ca 2+ ( [69] and references inside). Therefore, another reason that Tl + only stimulates the opening of MPTP pores in Ca 2+ -contained media could be weak interaction of Tl + with the SH groups [69].…”

“…Unlike Tl + , bivalent heavy metal ions (Cd 2+ , Hg 2+ , Pb 2+ , and Zn 2+ ) and Ag + possess high affinity to molecular SH groups and can stimulate the MPTP opening in media free of Ca 2+ ( [69] and references inside). Therefore, another reason that Tl + only stimulates the opening of MPTP pores in Ca 2+ -contained media could be weak interaction of Tl + with the SH groups [69]. It was shown that both the increase of cytoplasmic Ca 2+ concentration and various cytotoxic effects in experiments with isolated hepatocytes and Tl + were decreased in the presence of MPTP inhibitors (CsA and carnitine), which is in good correspondence with the inhibition of Tl + -induced MPTP opening in CaRLM in the presence of the MPTP inhibitors (CsA and ADP) [3].…”

Bacteriophage MS2 As a Tool for Targeted Delivery in Solid Tumor Chemotherapy

“…It has been demonstrated that Tl + ions exhibit strong cytotoxic activity and inhibit the cancer drug resistance-associated protein that acts as an efflux pump [4]. Incorporation of Tl + into a “non-leaking” nanosized container equipped with a targeted delivery system could allow one to develop an efficient tool for tumor destruction, while the overall toxicity of Tl + can be significantly mitigated.…”