Interaction of some Pd(II) complexes with Na+ / K+-ATPase: inhibition, kinetics, prevention and recovery.
The aim of this work was to investigate the influence of [PdCl4]2-, [PdCl(dien)]+ and [PdCl(Me4dien)]+ complexes on Na+ / K+-ATPase activity. The dose-dependent inhibition curves were obtained in all cases. IC50 values determined by Hill analysis were 2.25 x 10(-5) M, 1.21 x 10(-4) M and 2.36 x 10(-4) M, respectively. Na+ / K+-ATPase exhibited typical Michelis-Menten kinetics in the presence of Pd(II) complexes. Kinetic parameters (Vmax, Km) derived using Eadie-Hofstee transformation indicated a noncompetitive type of Na+ / K+-ATPase inhibition. The inhibitor constants (Ki) were determined from Dixon plots. The order of complex affinity for binding with Na+ / K+-ATPase, deducted from Ki values, was [PdCl4]2- > [PdCl(dien)]+ > [PdCl(Me4dien)]+. The results indicated that the potency of Pd(II) complexes to inhibit Na+/ K +-ATPase activity depended strongly on ligands of the related compound. Furthermore, the ability of SH-donor ligands, L-cysteine and glutathione, to prevent and recover the Pd(II) complexes-induced inhibition of Na+ / K+-ATPase was examined. The addition of 1 mM L-cysteine or glutathione to the reaction mixture before exposure to Pd(II) complexes prevented the inhibition by increasing the IC50 values by one order of magnitude. Moreover, the inhibited enzymatic activity was recovered by addition of SH-donor ligands in a concentration-dependent manner.
Krinulović
Katarina S
KS
Vinca Institute of Nuclear Sciences, Department of Physical Chemistry, P.O. Box 522, Belgrade 11001, Serbia & Montenegro.
Vasić
Vesna M
VM
D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003545:Cysteine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010165:Palladium / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013552:Swine
D004791:Enzyme Inhibitors; D010165:Palladium; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D003545:Cysteine