Na+/K+-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energy
source to drive excess Na+ions out of the cell in exchange for K+ions. We explored whether three representative
cytotoxic gold(III) compounds might interfere with Na+/K+-ATPase and cause its inhibition at pharmacologically
relevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy = 2,2′-bipyridine), [Au(pydmb
-
H)(CH3
COO)2] (pydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipydmb-H)(OH)][PF6]
(bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na+/K+-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na+/K+-ATPase inhibition.
It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes
Na+/K+-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energysource to drive excess Na+ions out of the cell in exchange for K+ions. We explored whether three representativecytotoxic gold(III) compounds might interfere with Na+/K+-ATPase and cause its inhibition at pharmacologicallyrelevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy = 2,2′-bipyridine), [Au(pydmb-H)(CH3COO)2] (pydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipydmb-H)(OH)][PF6](bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na+/K+-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na+/K+-ATPase inhibition.It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes
การแปล กรุณารอสักครู่..