Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria.
We studied action of inorganic phosphate (P(i)) on toxic effects of Tl+ in isolated rat liver mitochondria. This is a convenient model to study the toxicity of heavy metals. P(i) markedly retarded contraction of energized mitochondria swollen in the TlNO3 medium and even stronger stimulated swelling and state 4 of succinate-energized mitochondria in the TlNO3 medium. A valinomycin-induced decrease of K+-diffusion potential was also accelerated by Tl+ in the presence of P(i). The mitochondrial permeability transition pore in the medium containing Ca2+, TlNO3, and nitrates of univalent cations was distinctly stimulated by P(i). However, P(i) did not affect both the Tl+-stimulated swelling of nonenergized mitochondria in the TlNO3 medium and swelling of energized mitochondria in the Tl acetate medium. Respiration stimulated by 2,4-dinitrophenol and monoamine oxidase activity of energized mitochondria were not affected by Tl+ regardless of the presence of P(i). We suggested that stimulation by P(i) of toxic action of Tl+ in mitochondria and cells could be due to even greater enhancement of uncoupling of mitochondria as shown by an additional increase of swelling and state 4, and in the greater probability of opening of MPTP in the presence of P(i) and Ca2+.
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223 St. Petersburg, Russia. korotkov@SK1645.spb.edu
Sergey M
SM
Korotkov
Larisa V
LV
Emel'yanova
Olga V
OV
Yagodina
D000818:Animals; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects*; D008995:Monoamine Oxidase / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013793:Thallium / Q000378:metabolism / Q000633:toxicity*
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009942:Organometallic Compounds; D010710:Phosphates; D013793:Thallium; D008995:Monoamine Oxidase; C042172:thallium nitrate; C026995:thallium acetate