The Joint Influence of Tl+ and Thiol-Modifying Agents on Rat Liver Mitochondrial Parameters In Vitro

Recent data have shown that the mitochondrial permeability transition pore (MPTP) is the complex of the Ca2+-modified adenine nucleotide translocase (ANT) and the Ca2+-modified ATP synthase. We found in a previous study that ANT conformational changes may be involved in Tl+-induced MPTP opening in the inner membrane of Ca2+-loaded rat liver mitochondria. In this study, the effects of thiol-modifying agents (eosin-5-maleimide (EMA), fluorescein isothiocyanate (FITC), Cu(o-phenanthroline)(2) (Cu(OP)(2)), and embelin (Emb)), and MPTP inhibitors (ADP, cyclosporine A (CsA), n-ethylmaleimide (NEM), and trifluoperazine (TFP)) on MPTP opening were tested simultaneously with increases in swelling, membrane potential (Delta psi(mito)) decline, decreases in state 3, 4, and 3U(DNP) (2,4-dinitrophenol-uncoupled) respiration, and changes in the inner membrane free thiol group content. The effects of these thiol-modifying agents on the studied mitochondrial characteristics were multidirectional and showed a clear dependence on their concentration. This research suggests that Tl+-induced MPTP opening in the inner membrane of calcium-loaded mitochondria may be caused by the interaction of used reagents (EMA, FITC, Emb, Cu(OP)(2)) with active groups of ANT, the mitochondrial phosphate carrier (PiC) and the mitochondrial respiratory chain complexes. This study provides further insight into the causes of thallium toxicity and may be useful in the development of new treatments for thallium poisoning.

Automated summary

This study found that the effects of thiol-modifying agents and MPTP inhibitors on MPTP opening were diverse and concentration-dependent. The research suggests that Tl+-induced MPTP opening in calcium-loaded mitochondrial inner membrane may be caused by the interaction of active groups. This study provides further insight into the causes of thallium toxicity and may be useful in developing new treatments for thallium poisoning.