Abstract
The effects of both Tl+ and thiol reagents were studied on the content of the inner membrane free SH-groups, detected with Ellman reagent, and the inner membrane potential as well as swelling and respiration of succinate-energized rat liver mitochondria in medium containing TlNO3 and KNO3. These effects resulted in a rise in swelling and a decrease in the content, the potential, and mitochondrial respiration in 3 and 2,4-dinitrophenol-uncoupled states. A maximal effect was seen when phenylarsine oxide reacting with thiol groups recessed into the hydrophobic regions of the membrane. Compared with phenylarsine oxide, the effective concentrations of other reagents were approximately one order of magnitude higher in experiments with mersalyl and 4,4′-diisothiocyanostilbene-2,2′-disulfonate, and two orders of magnitude higher in experiments with tert-butyl hydroperoxide and diamide. The above effects of Tl+ and the thiol reagents became even more pronounced with calcium overload of mitochondria. However, the effects were suppressed by inhibitors of the mitochondrial permeability transition pore (cyclosporine A, ADP, and n-ethylmaleimide). These findings suggest that opening of the pore induced by Tl+ in the inner membrane can be dependent on the conformation state of the adenine nucleotide translocase, which depends on the activity of its thiol groups.
Similar content being viewed by others
Abbreviations
- ΔΨmito :
-
Inner mitochondrial membrane potential
- ANT:
-
Adenine nucleotide translocase
- CsA:
-
Cyclosporine A
- CyP-D:
-
Cyclophilin D
- Diam:
-
Diamide
- DIDS:
-
4,4′-Diisothiocyanostilbene-2,2′-disulfonate
- DNP:
-
2,4-Dinitrophenol
- DTNB:
-
5,5-Dithio-bis-nitrobenzoic acid
- DTT:
-
Dithiothreitol
- EDTA:
-
Ethylenediaminetetraacetic acid
- EGTA:
-
Ethylene glycol-bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid
- IMM:
-
Inner mitochondrial membrane
- MPTP:
-
Mitochondrial permeability transition pore
- MSL:
-
Mersalyl
- NEM:
-
n-Ethylmaleimide
- PAO:
-
Phenylarsine oxide
- PiC:
-
Mitochondrial phosphate carrier
- RLM:
-
Rat liver mitochondria
- SDS:
-
Sodium dodecyl sulfate
- tBHP:
-
Tert-butyl hydroperoxide
References
Aoyama H, Yoshida M, Yamamura Y (1988) Induction of lipid peroxidation in tissues of thallous malonate-treated hamster. Toxicology 53(1):11–18. https://doi.org/10.1016/0300-483x(88)90232-6
Barrera H, Gomez-Puyou A (1975) Characteristics of the movement of K+ across the mitochondrial membrane and the inhibitory action of Tl+. J Biol Chem 250(14):5370–5374
Bernardes CF, Meyer-Fernandes JR, Basseres DS, Castilho RF, Vercesi AE (1994) Ca2+-dependent permeabilization of the inner mitochondrial membrane by 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS). Biochim Biophys Acta 1188(1–2):93–100. https://doi.org/10.1016/0005-2728(94)90026-4
Bernardes CF, Meyer-Fernandes JR, Martins OB, Vercesi AE (1997) Inhibition of succinic dehydrogenase and F0F1-ATP synthase by 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS). Z Naturforsch C 52(11–12):799–806. https://doi.org/10.1515/znc-1997-11-1212
Bindoli A, Callegaro MT, Barzon E, Benetti M, Rigobello MP (1997) Influence of the redox state of pyridine nucleotides on mitochondrial sulfhydryl groups and permeability transition. Arch Biochem Biophys 342(1):22–28. https://doi.org/10.1006/abbi.1997.9986
Bragadin M, Toninello A, Bindoli A, Rigobello MP, Canton M (2003) Thallium induces apoptosis in Jurkat cells. Ann N Y Acad Sci 1010:283–291. https://doi.org/10.1196/annals.1299.049
Bramanti E, Onor M, Colombaioni L (2019) Neurotoxicity induced by low thallium doses in living hippocampal neurons: evidence of early onset mitochondrial dysfunction and correlation with ethanol production. ACS Chem Neurosci 10(1):451–459. https://doi.org/10.1021/acschemneuro.8b00343
Brierley GP, Knight VA, Settlemire CT (1968) Ion transport by heart mitochondria. XII Activation of monovalent cation uptake by sulfhydrly group reagents. J Biol Chem 243(19):5035–5043
Brierley GP, Jurkowitz M, Scott KM, Merola AJ (1970) Ion transport by heart mitochondria. XX. Factors affecting passive osmotic swelling of isolated mitochondria. J Biol Chem 245(20):5404–5411
Bugarin MG, Casas JS, Sordo J, Filella M (1989) Thallium (I) interactions in biological fluids: a potentiometric investigation of thallium(I) complex equilibria with some sulphur-containing amino acids. J Inorg Biochem 35(2):95–105. https://doi.org/10.1016/0162-0134(89)80002-9
Bunni MA, Douglas KT (1984) Arylthallium(III) reagents for protein modification Inhibition of lactate dehydrogenase from various sources by o-carboxyphenylthallium(III) bistrifluoroacetate. Biochem J 217(2):383–390. https://doi.org/10.1042/bj2170383
Carraro M, Carrer A, Urbani A, Bernardi P (2020) Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection. J Mol Cell Cardiol 144:76–86. https://doi.org/10.1016/j.yjmcc.2020.05.014
Castilho RF, Kowaltowski AJ, Meinicke AR, Bechara EJH, Vercesi AE (1995) Permeabilization of the inner mitochondrial membrane by Ca2+ ions is stimulated by t-butyl hydroperoxide and mediated by reactive oxygen species generated by mitochondria. Free Radical Biol Med 18(3):479–486. https://doi.org/10.1016/0891-5849(94)00166-h
Castilho RF, Kowaltowski AJ, Vercesi AE (1996) The irreversibility of inner mitochondrial membrane permeabilization by Ca2+ plus prooxidants is determined by the extent of membrane protein thiol crosslinking. J Bioenerg Biomembr 28(6):523–539. https://doi.org/10.1007/BF02110442
Chandler HA, Scott M (1986) A review of thallium toxicology. J R Nav Med Serv 72(2):75–79
Connern CP, Halestrap AP (1994) Recruitment of mitochondrial cyclophilin to the mitochondrial inner membrane under conditions of oxidative stress that enhance the opening of a calcium-sensitive non-specific channel. Biochem J 302(Pt 2):321–324. https://doi.org/10.1042/bj3020321
Douglas KT, Bunni MA, Baindur SR (1990) Thallium in biochemistry. Int J Biochem 22(5):429–438. https://doi.org/10.1016/0020-711x(90)90254-z
Ellman GL (1959) Tissue thiol groups. Arch Biochem Biophys 82(1):70–77. https://doi.org/10.1016/0003-9861(59)90090-6
Flesh P, Goldstone SB (1950) Effect of thallium on sulphydryl compounds in vitro. J Invest Dermatol 15(5):345–347. https://doi.org/10.1038/jid.1950.111
Galván-Arzate S, Santamaría A (1998) Thallium toxicity. Toxicol Lett 99(1):1–13. https://doi.org/10.1016/s0378-4274(98)00126-x
Galván-Arzate S, Pedraza-Chaverrí J, Medina-Campos ON, Maldonado PD, Vázquez-Román B, Ríos C, Santamaría A (2005) Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration. Food Chem Toxicol 43(7):1037–1045. https://doi.org/10.1016/j.fct.2005.02.006
García N, Martínez-Abundis E, Pavón N, Chávez E (2007) On the opening of an insensitive cyclosporine A non-specific pore by phenylarsine plus mersalyl. Cell Biochem Biophys 49(2):84–90. https://doi.org/10.1007/s12013-007-0047-0
Gross P, Runne E, Wilson JW (1948) Studies on the effect of thallium poisoning of the rat; the influence of cystine and methionine on alopecia and survival periods. J Investig Dermatol 10(3):119–134. https://doi.org/10.1038/jid.1948.20
Halestrap AP (2010) A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection. Biochem Soc Trans 38(4):841–860. https://doi.org/10.1042/BST0380841
Halestrap AP, Brenner C (2003) The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem 10(16):1507–1525. https://doi.org/10.2174/0929867033457278
Halestrap AP, Woodfield KY, Connern CP (1997) Oxidative stress, thiol reagents, and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase. J BiolChem 272(6):3346–3354. https://doi.org/10.1074/jbc.272.6.3346
Hanzel CE, Verstraeten SV (2009) Tl(I) and Tl(III) activate both mitochondrial and extrinsic pathways of apoptosis in rat pheochromocytoma (PC12) cells. Toxicol Appl Pharmacol 236(1):59–70. https://doi.org/10.1016/j.taap.2008.12.029
Hasan M, Chandra SV, Dua PR, Raghubir R, Ali SF (1977) Biochemical and electrophysiologic effects of thallium poisoning on the rat corpus striatum. Toxicol Appl Pharmacol 41(2):353–359. https://doi.org/10.1016/0041-008x(77)90036-9
Herman MM, Bensch KG (1967) Light and electron microscopic studies of acute and chronic thallium intoxication in rats. Toxicol Appl Pharmacol 10(2):199–222. https://doi.org/10.1016/0041-008x(67)90104-4
Houstĕk J, Pedersen PL (1985) Adenine nucleotide and phosphate transport systems of mitochondria Relative location of sulfhydryl groups based on the use of the novel fluorescent probe eosin-5-maleimide. J Biol Chem 260(10):6288–6295
Huang CC, Shih TS, Liu CH (2012) Acute thallium intoxication: an experience in Taiwan. Curr Top Toxicol 8:33–41
Ichas F, Mazat JP (1998) From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim Biophys Acta 1366(1–2):33–50. https://doi.org/10.1016/s0005-2728(98)00119-4
Kiliç GA, Kutlu M (2010) Effects of exogenous metallothionein against thallium-induced oxidative stress in rat liver. Food Chem Toxicol 48(3):980–987. https://doi.org/10.1016/j.fct.2010.01.013
Korotkov SM (2009) Effects of Tl+ on ion permeability, membrane potential and respiration of isolated rat liver mitochondria. J Bioenerg Biomembr 41(3):277–287. https://doi.org/10.1007/s10863-009-9225-7
Korotkov SM (2013) Thallium, effects on mitochondria. In: Kretsinger RH, Uversky VN, Permyakov EA (eds) Encyclopedia of metalloproteins. Springer, New York, pp 2193–2202
Korotkov SM, Saris NE (2011) Influence of Tl+ on mitochondrial permeability transition pore in Ca2+-loaded rat liver mitochondria. J Bioenerg Biomembr 43(2):149–162. https://doi.org/10.1007/s10863-011-9341-z
Korotkov SM, Skulskii IA, Glazunov VV (1998) Cd2+ effects on respiration and swelling of rat liver mitochondria were modified by monovalent cations. J Inorg Biochem 70(1):17–23. https://doi.org/10.1016/s0162-0134(98)00008-7
Korotkov SM, Glazunov VV, Yagodina OV (2007) Increase in toxic effects of Tl+ on isolated rat liver mitochondria in the presence of nonactin. J Biochem Mol Toxicol 21(2):81–91. https://doi.org/10.1002/jbt.20163
Korotkov SM, Emel’yanova LV, Yagodina OV (2008) Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria. J Biochem Mol Toxicol 22(3):148–157. https://doi.org/10.1002/jbt.20215
Korotkov SM, Brailovskaya IV, Kormilitsyn BN, Furaev VV (2014a) Tl+ showed negligible interaction with inner membrane sulfhydryl groups of rat liver mitochondria, but formed complexes with matrix proteins. J Biochem Mol Toxicol 28(4):149–156. https://doi.org/10.1002/jbt.21547
Korotkov S, Konovalova S, Emelyanova L, Brailovskaya I (2014b) Y3+, La3+, and some bivalent metals inhibited the opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria. J Inorg Biochem 141(1):1–9
Korotkov SM, Konovalova SA, Brailovskaya IV (2015a) Diamide accelerates opening of the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria. Biochim Biophys Res Commun 468(1–2):360–364. https://doi.org/10.1016/j.bbrc.2015.10.091
Korotkov SM, Emelyanova LV, Konovalova SA, Brailovskaya IV (2015b) Tl+ induces the permeability transition pore in Ca2+-loaded rat liver mitochondria energized by glutamate and malate. Toxicol in Vitro 29(5):1034–1041. https://doi.org/10.1016/j.tiv.2015.04.006
Korotkov SM, Konovalova SA, Brailovskaya IV, Saris NEL (2016) To involvement the conformation of the adenine nucleotide translocase in opening the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria. Toxicol in Vitro 32:320–332. https://doi.org/10.1016/j.tiv.2016.01.015
Korotkov SM, Konovalova SA, Nesterov VP, Brailovskaya IV (2018) Mersalyl prevents the Tl+-induced permeability transition pore opening in the inner membrane of Ca2+-loaded rat liver mitochondria. Biochem Biophys Res Commun 495(2):1716–1721. https://doi.org/10.1016/j.bbrc.2017.12.023
Kotlyar AB, Vinogradov AD (1984) Interaction of the membrane-bound succinate dehydrogenase with substrate and competitive inhibitors. Biochim Biophys Acta 784(1):24–34. https://doi.org/10.1016/0167-4838(84)90168-7
Kowaltowski AJ, Vercesi AE, Castilho RF (1997) Mitochondrial membrane protein thiol reactivity with N-ethylmaleimide or mersalyl is modified by Ca2+: correlation with mitochondrial permeability transition. Biochim Biophys Acta 1318(3):395–402. https://doi.org/10.1016/s0005-2728(96)00111-9
Lenartowicz E, Bernardi P, Azzone GF (1991) Phenylarsine oxide induces the cyclosporin A-sensitive membrane permeability transition in rat liver mitochondria. J Bioenerg Biomembr 23(4):679–688. https://doi.org/10.1007/BF00785817
Lê-Quôc K, Lê-Quôc D (1985) Crucial role of sulfhydryl groups in the mitochondrial inner membrane structure. J Biol Chem 260(12):7422–7428
Leung KM, Ooi VE (2000) Studies on thallium toxicity, its tissue distribution and histopathological effects in rats. Chemosphere 41(1–2):155–159. https://doi.org/10.1016/s0045-6535(99)00404-x
Lin G, Sun Y, Long J, Sui X, Yang J, Wang Q, Wang S, He H, Luo Y, Qiu Z, Wang Y (2020) Involvement of the Nrf2-Keap1 signaling pathway in protection against thallium-induced oxidative stress and mitochondrial dysfunction in primary hippocampal neurons. Toxicol Lett 319:66–73. https://doi.org/10.1016/j.toxlet.2019.11.008
Maya-López M, Mireles-García MV, Ramírez-Toledo M, Colín-González AL, Galván-Arzate S, Túnez I, Santamaría A (2018) Thallium-induced toxicity in rat brain crude synaptosomal/mitochondrial fractions is sensitive to anti-excitatory and antioxidant agents. Neurotox Res 33(3):634–640. https://doi.org/10.1007/s12640-017-9863-1
McStay GP, Clarke SJ, Halestrap AP (2002) Role of critical thiol groups on the matrix surface of the adenine nucleotide translocase in the mechanism of the mitochondrial permeability transition pore. Biochem J 367(Pt 2):541–548. https://doi.org/10.1042/BJ20011672
Melnick RL, Monti LG, Motzkin SM (1976) Uncoupling of mitochondrial oxidative phosphorylation by thallium. Biochem Biophys Res Commun 69(1):68–73. https://doi.org/10.1016/s0006-291x(76)80273-2
Mulkey JP, Oehme FW (1993) A review of thallium toxicity. Vet Hum Toxicol 35(5):445–453
Novgorodov SA, Kultayeva EV, Yaguzhinsky LS, Lemeshko VV (1987) Ion permeability induction by the SH crosslinking reagents in rat liver mitochondria is inhibited by the free radical scavenger, butylhydroxytoluene. J Bioenerg Biomembr 19(3):191–202. https://doi.org/10.1007/BF00762412
Panov A, Schonfeld P, Dikalov S, Hemendinger R, Bonkovsky HL, Brooks BR (2009) The neuromediator glutamate, through specific substrate interactions, enhances mitochondrial ATP production and reactive oxygen species generation in nonsynaptic brain mitochondria. J Biol Chem 284(21):14448–14456. https://doi.org/10.1074/jbc.M900985200
Perrin DD (1979) Stability constants of metal-ion complexes. Part B. Organic ligands. Pergamon, Oxford
Petronilli V, Costantini P, Scorrano L, Colonna R, Passamonti S, Bernardi P (1994) The voltage sensor of the mitochondrial permeability transition pore is tuned by the oxidation-reduction state of vicinal thiols. Increase of the gating potential by oxidants and its reversal by reducing agents. J Biol Chem 269(24):16638–16642
Petronilli V, Sileikyte J, Zulian A, Dabbeni-Sala F, Jori G, Gobbo S, Tognon G, Nikolov P, Bernardi P, Ricchelli F (2009) Switch from inhibition to activation of the mitochondrial permeability transition during hematoporphyrin-mediated photooxidative stress Unmasking pore-regulating external thiols. Biochim Biophys Acta 1787(7):897–904. https://doi.org/10.1016/j.bbabio.2009.03.014
Pourahmad J, Eskandari MR, Daraei B (2010) A comparison of hepatocyte cytotoxic mechanisms for thallium (I) and thallium (III). Environ Toxicol 25(5):456–467. https://doi.org/10.1002/tox.20590
Riley MV, Lehninger AL (1964) Changes in sulfhydryl groups of rat liver mitochondria during swelling and contraction. J Biol Chem 239(6):2083–2089
Riley WW Jr, Pfeiffer DR (1985) Relationships between Ca2+ release, Ca2+ cycling, and Ca2+-mediated permeability changes in mitochondria. J Biol Chem 260(23):12416–12425
Rodríguez-Mercado JJ, Altamirano-Lozano MA (2013) Genetic toxicology of thallium: a review. Drug Chem Toxicol 36(3):369–383. https://doi.org/10.3109/01480545.2012.710633
Saris NE, Skulskii IA, Savina MV, Glasunov VV (1981) Mechanism of mitochondrial transport of thallous ions. J Bioenerg Biomembr 13(1–2):51–59. https://doi.org/10.1007/BF00744746
Schoer J (1984) Thallium. In: Hutzinger O (ed) Handbook of environmental chemistry anthropogenic compounds. Springer, New York
Scott KM, Hwang KM, Jurkowitz M, Brierley GP (1971) Ion transport by heart mitochondria 23 The effects of lead on mitochondrial reactions. Arch Biochem Biophys 147(2):557–567. https://doi.org/10.1016/0003-9861(71)90413-9
Singh BK, Tripathi M, Pandey PK, Kakkar P (2011) Alteration in mitochondrial thiol enhances calcium ion dependent membrane permeability transition and dysfunction in vitro: a cross-talk between mtThiol, Ca2+, and ROS. Mol Cell Biochem 357(1–2):373–385. https://doi.org/10.1007/s11010-011-0908-0
Spencer PS, Peterson ER, Madrid R, Raine CS (1973) Effects of thallium salts on neuronal mitochondria in organotypic cord-ganglia-muscle combination cultures. J Cell Biol 58(1):79–95. https://doi.org/10.1083/jcb.58.1.79
Stavinoha WB, Emerson GA, Nash JB (1959) The effects of some sulfur compounds on thallotoxicosis in mice. Toxicol Appl Pharmacol 1:638–646. https://doi.org/10.1016/0041-008x(59)90068-7
Varanyuwatana P, Halestrap AP (2012) The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore. Mitochondrion 12(1):120–125. https://doi.org/10.1016/j.mito.2011.04.006
Waldmeier PC, Feldtrauer JJ, Qian T, Lemasters J (2002) Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol Pharmacol 62(1):22–29. https://doi.org/10.1124/mol.62.1.22
Weinberg JM, Harding PG, Humes HD (1982) Mitochondrial bioenergetics during the initiation of mercuric chloride-induced renal injury I. Direct effects of in vitro mercuric chloride on renal cortical mitochondrial function. J Biol Chem 257(1):60–67
Woods JS, Fowler BA (1986) Alteration of hepatocellular structure and function by thallium chloride: ultrastructural, morphometric, and biochemical studies. Toxicol Appl Pharmacol 83(2):218–229. https://doi.org/10.1016/0041-008x(86)90299-1
Woods JS, Fowler BA, Eaton DL (1984) Studies on the mechanisms of thallium-mediated inhibition of hepatic mixed function oxidase activity. Correlation with inhibition of NADPH-cytochrome c (P-450) reductase. Biochem Pharmacol 33(4):571–576. https://doi.org/10.1016/0006-2952(84)90309-5
Zazueta C, Sánchez C, García N, Correa F (2000) Possible involvement of the adenine nucleotide translocase in the activation of the permeability transition pore induced by cadmium. Int J Biochem Cell Biol 32(10):1093–1101. https://doi.org/10.1016/s1357-2725(00)00041-8
Zierold K (2000) Heavy metal cytotoxicity studied by electron probe X-ray microanalysis of cultured rat hepatocytes. Toxicol in Vitro 14(6):557–563. https://doi.org/10.1016/s0887-2333(00)00049-7
Acknowledgements
The author is grateful to Ms Terttu Kaustia for correcting the English as well as Irina V. Brailovskaya, Victor V. Furaev, and Boris N. Kormilitsyn for help in isolating mitochondria and estimation of the protein thiol content and the oxygen consumption rates in rat liver mitochondrial suspensions. The research was carried out within the state assignment of FASO of Russia (theme No. AAAA-A18-118012290142-9). Safranin fluorescence was measured using of Research Resource Center equipment for the physiological, biochemical and molecular-biological studies (Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No conflicts of interest, financial or otherwise, are declared by the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Korotkov, S.M. Effects of Tl+ on the inner membrane thiol groups, respiration, and swelling in succinate-energized rat liver mitochondria were modified by thiol reagents. Biometals 34, 987–1006 (2021). https://doi.org/10.1007/s10534-021-00329-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-021-00329-6