Extracellular and intracellular biospeciaciation of insulin-mimetic metal complexes  Page description

Help  Print 
Back »
 

Details of project

  
Identifier
49417
Type K
Principal investigator Kiss, Tamás
Title in Hungarian Inzulinutánzó fémkomplexek biospeciációja a sejten kívüli és a sejten belüli térben
Title in English Extracellular and intracellular biospeciaciation of insulin-mimetic metal complexes
Panel Chemistry 1
Department or equivalent Department of Molecular and Analytical Chemistry (University of Szeged)
Participants Dörnyei, Ágnes
Jakusch, Tamás
Károlyné Lakatos, Andrea
Schrantz, Krisztina
Starting date 2005-01-01
Closing date 2009-12-31
Funding (in million HUF) 11.700
FTE (full time equivalent) 5.20
state closed project





 

Final report

  
Results in Hungarian
Antidiabetikus hatású VO(IV) és Zn(II) komplexek lehetséges átalakulásait vizsgáltuk a sejten kívüli és a sejten belüli térben, hogy felvilágosítást kapjunk a legvalószínűbb kémiai formára (biospeciáció), amely kapcsolatba hozható a biológiai aktivitással. Megállapítottuk, hogy a sejten kívüli térben mindkét fém esetében elsősorban a nagy molakulatömegű fehérjék a felelősek a fémionok/komplexek szállításáért, a VO(IV) komplexek esetén a Tf, míg a Zn(II) komplexek esetén a HSA. A kis molekulatömegű szérum komponensek, a citrát, illetve a His és Cys szerepe sem elhanyagolható, mivel ezek jelentik a fémion könnyen mobilizálható formáját. Az eredeti hordozó ligandumok, bár kölcsönhatásukat e szérum fehérjékkel (elsősorban a HSA-nal kimutattuk, úgy tűnik elsősorban a fémionok felszívódásának fokozásában van. Modell vizsgálatainkat és számításainkat ultraszűréssel, valamint ionkromatográfia-ICP(MS), illetve kapillárelektroforézis-ICP(MS) vizsgálatokkal igazoltuk. A fémionok sejten belüli lehetséges átalakulásait a mM koncentrációban jelenlevő glutation (GSH) és adenozin-trifoszfát (ATP) ligandumokkal vizsgáltuk. Megállapítottuk, hogy a VO(IV) esetén a GSH elsősorban a vanádium oxidációs állapotának meghatározásában és fenntartásában (alapvetően +4), míg az ATP a biner és terner komplexekben való megkötéséban játszik szerepet. Ugyanakkor a Zn(II)-nél a vegyes ligandumú komplexképződéssel a hordozó komplexek és az ATP, illetve a GSH között gyakorlatilag minden esetben számolni kell.
Results in English
The possible transformation reactions of potential antidiabetic VO(IV) and Zn(II) complexes were studied extracellurarly and intracellurarly in order to obtain information for the most probable chemical form (biospeciation) existing in the system and thus might be responsible for the biological activity. It was found that the high molecular mass serum proteins are the primary metal ion transporters with both metal ions and/or their complexes; in the case of VO(IV) the Tf, while in the case of Zn(II) HSA. The role of the low molecular mass components of serum like citrate or His and Cys are also important, as they may be the mobile form of the metal ions. The original carrier ligands, although their interactions with the serum proteins were detected possibly only facilitate absorption. The results of the modeling studies and calculations were confirmed by ultrafiltration and ionchromatography-ICP(MS) or capillaryelectrophoresis-ICP(MS) combined techniques on human serum samples. In the cell, the possible transformations of these complexes were studied with glutathione (GSH) and adenosine.triphosphate (ATP) both being present in mM concentration in the cell. It was found that in the case of VO(IV) complexes the primary role of GSH is its redox activity, while ATP as a strong complexing agent will bind VO(IV) in binary and ternary complexes. At he same time in the case of Zn(II) ternary complex formation between the carrier complexes and GSH or ATP may be important in any cases.
Full text http://real.mtak.hu/1970/
Decision
Yes





 

List of publications

  
Kiss T; Jakusch T; Bouhsina S; Sakurai H; Enyedi ÉA,: Binding Constant of VO(IV) to Transferrin, Eur. J. Inorg. Chem., 3607-3614, 2006
Jakusch T; Marcao S; Rodrigues L; Correia I; Costa Pessoa J; Kiss T: Oxovanadium(IV) complexes of salicyl-L-aspartic acid and salicyiglicyl-L-aspartic acid, Dalton Transactions, 2005, 3072-3078, 2005
Correia I; Dörnyei Á; Avecilla F; Kiss T;, Costa Pessoa J: X-ray Diffraction and aqueous characterization of Zn(II)[N,N’-ethylendi(pyridoxylaminato)], Eur.J.Inorg.Chem., 3, 656-662, 2006
Jakusch T; Gajda-Schrantz K; Adachi Y; Sakurai H; Kiss T: Solution equilibrium characterisation of insulin-mimetic Zn(II) complexes, J. Inorg. Biochem., 100 1521-1526, 2006
Kiss T; Jakusch T, Hollender D; Dörnyei Á;: Biospeciation of Insulin-mimetic VO(IV) complexes, ACS Special Publication Symposium Series 974, 323-339, 2007
Dörnyei Á; Kiss T; Bouhsina S; Marcao S; Costa Pessoa J: Interactions of insulin mimetic VO(IV) complexes with cell constituents: ATP and glutathione, 1st European Conference on Chemistry for Life Sciences, Rimini, October 4-8, 2005, p200, 2005
Dörnyei Á; Marcao S; Pessoa JC; Jakusch T; Kiss T;: Interactions of Insulin-mimetic VO(IV) complexes with Cell Constituents ATP and Glutathione, European Journal of Inorganic Chemistry, (18), 3614-3621, 2006
Enyedy ÉA; horváth L; Gajda.Schrantz K; Galbács G; Kiss T ,: An in vitro study of interactions between insulin-mimetic zinc(II) complexes and selected plasma components, J. Inorg. Biochem., 100, 1936-1945, 2006
Adachi Y; YoshidaJ; Kodera Y; Kiss T; Jakusch T; Enyedy ÉA; Yoshikawa Y; Sakurai H,: Oral Administration of a zinc complex improves type 2 diabetes and metabolic syndromes, Biochem. Biophys Res. Commun., 351, 165-170, 2006
Dörnyei Á; Marcao S; Pessoa JC; Jakusch T; Kiss T,: Interactions of insulin mimetic VO(IV) complexes with cell constituents: ATP and glutathione, European J. Inorg. Chem., 3614-3621, 2006
Kiss T; Jakusch T; Hollender D; Dörnyei A; Enyedy ÉA; Pessoa JC; Sakurai H; Sanz-Medel,: Biospeciation of insulin mimetic VO(IV) complexes, Coord. Chem. Rev. , 252, 1153-1162, 2008, 2008
Kiss T; Odani A,: Demonstration of the importance of metral ion speciation in bioactive systems, Bull. Chem. Soc. Japan, 80, 1691-1702, 2007
Enyedy ÉA; Lakatos A; Kiss T; Horváth L; Kiss T,: Interactions of insulin-mimetic zinc(II) complexes with cell constituents: glutathione and ATP, J. Inorg. Biochem., 102, 1473-1485, 2008, 2008
Dörnyei Á; Marcao S; Pessoa JC; Jakusch T; Kiss T,: Interactions of insulin-mimetic vanadium(IV) complexes with cell constituents: glutathione and ATP, 2nd European Conference on Chemistry for Life Sciences, 4-8 Sept. 200, Wroclaw, Poland, 2007
Dörnyei Á; Marcao S; Pessoa JC; Jakusch T; Kiss T,: Interactions of insulin-mimetic vanadium(IV) complexes with cell constituents: glutathione and ATP, 2nd European Conference on Chemistry for Life Sciences, 4-8 Sept. 200, Wroclaw, Poland, p159, 2007
Enyedy ÉA; Horváth L; Kiss T,: Interactions of insulin-mimetic zinc(II) complexes and their carrier ligands with cell constituents, 2nd European Conference on Chemistry for Life Sciences, 4-8 Sept. 200, Wroclaw, Poland, p168, 2007
Horváth L; Enyedy ÉA; Lakatos A; Kiss T,: Solution studies on ternary complex formation of insulin-mimetic zinc(II) complexes with glutathione and ATP, 2nd European Conference on Chemistry for Life Sciences, 4-8 Sept. 200, Wroclaw, Poland, p194, 2007
Kiss T,: Speciation of Bioactive insulin-mimetic VO(IV) complexes, 2nd European Conference on Chemistry for Life Sciences, 4-8 Sept. 200, Wroclaw, Poland, p50, 2007
Kiss T,: Biospeciation of insulin-mimetic vanadium(IV) complexes, ISMEC 2007, 5-9 June. 2007, Cagliari, Italy, p3 (plenary lecture), 2007
Enyedy ÉA; Horváth L; Károly-Lakatos A; Kiss T,: Interaction of insulin-mimetic zinc(II) complexes with the cell constituent glutathione, XXI International Conference on Coordination and Bioinorganic Chemistry, 3-8 June 2007, Smolenice, Slovakia, p25, 2007
Kiss T; Jakusch T; Hollender D; Dörnyei Á.: Inzulinutánzó vanádium(IV) komplexek biospeciációja (szekcióelőadás), Centenáriumi Vegyészkonferencia, Május 29-Junius 1 2007, Sopron, p277., 2007
Horváth L; Kiss T; Enyedy ÉA; Lakatos A,: Inzulinutánzó cink(II) komplexek lölcsönhatása glutationnal, XLII. Komplexkémiai Kollokvium, 2007. május 23-25, Mátrafüred, p19, 2007
Nikolakis VA, Tsalavoutis, JT, Stylianou M, Evegeniou E, Jakusch T, Melman A, Sigalas, MP, Kiss T, Keramidas, AD, Kabanos TA,: Vanadium(V) compounds with the bis(hydoxylamino)1,3,5-triazine ligand, H(2)bihyat: synthetic, structural and physical studies of [(V2O3)-OV(bihyat)(2)] and of the enhanced hydrolitic stability species cis-[(VO2)-O-V(bihyat)](-), Inorg. Chem., 47 11698-11710, 2008
Hossein Esbak, Jessica Nilsson, Ebbe Nordlander, E. A. Enyedy, Tamas Kiss, Yutaka Yoshikawa, Hiromu Sakurai, Dieter, Rehder: Insulin-mimetic and speciation studies of oxovanadium complexes containing picolyltryptophane and tris(pyridyl)amine, J. Arg. Chem. Soc.,, 2008
Hossein Esbak, E. A. Enyedy, Tamas Kiss, Yutaka Yoshikawa, Hiromu Sakurai, Eugenio Garribba, Dieter, Rehder: Amninoacid-derivatised pivcolynato-oxovanadium(IV) complexes: characterisation, speciation and ex vivo insulin-mimetic potential, J. Inorg. Biochem., (in press), 2008
Tamas Kiss, Tamás Jakusch, Dominik Hollender, Éva Anna Enyedy, László Horváth: Comparative studies on the biospeciation of anti-diabetic VO(IV) and Zn(II) complrexes, J. Inorg. Biochem., (in press), 2008
T. Jakusch, D. Hollender, É. A. Enyedy, C.S. González, M. Montes-Bayon, A. Sanz-Medel, J. Costa Pessoa, I. Tomaz, T. Kiss: Biospeciation of different antidiabetic VO(IV) compounds with serum proteins, Dalton Trans., (in press), 2009



Back »