Role of Na+, K+-ATPase α1 subunit in the intracellular accumulation of cisplatin

Kishimoto, Seiji; Kawazoe, Yuji; Ikeno, Mako; Saitoh, Mizuha; Nakano, Yukari; Nishi, Yuko; Fukushima, Shoji; Takeuchi, Yoshikazu

doi:10.1007/s00280-005-0003-x

Cited by 39 publications

(28 citation statements)

References 23 publications

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“…This gender-dependent effect was stimulus specific (13). Furthermore, the Na,K-ATPase alpha 1 subunit expression was decreased following a 24-h exposure to CP, and these results suggest that Na,K-ATPasedependent active transport of CP does not occur in resistant cells, and furthermore, the Na,K-ATPase alpha 1 subunit plays an important role in the transport of cisplatin (14). Data from several studies indicated decreased function of the Na,K-ATPase pump in female heart, ileum, liver, brain tissues as compared to male ones (15).…”

Section: Discussionmentioning

confidence: 64%

Cisplatin increases urinary sodium excretion in rats: gender-related differences

et al. 2010

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Results. The 24-h urinary sodium excretion, sodium/chloride ratio, and diuresis showed no gender-related differences in control rats. After a single administration of 2.5 mg/kg cisplatin, 24-h urinary sodium excretion was not significantly higher in cisplatin-treated rats than in gender-matched controls. After repeated cisplatin administration, 24-h urinary sodium excretion was significantly higher in cisplatin-treated male rats as compared to matched controls (P<0.05). No such effect was found in cisplatin-treated female rats.Conclusion. The study data show that cisplatin enhances urinary sodium excretion in male but not in female rats. The mechanism of such a gender-related effect is not yet clear. Further investigations are necessary to elucidate the mechanism of this pharmacological effect of cisplatin.

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Section: Discussionmentioning

confidence: 64%

Cisplatin increases urinary sodium excretion in rats: gender-related differences

et al. 2010

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“…As mentioned above, cisplatin ( cis -diaminedichloroplatinum) is also a potent anticancer drug [106-108]. It is well known that cisplatin inhibits Na + ,K + -ATPase, but rather a high cisplatin concentration (280-800 μM) and/or a long period of incubation (60-90 min) was required to obtain about 50% inhibition of enzyme activity.…”

Section: Inhibition Of Na+k+-atpase Activitymentioning

confidence: 99%

Na+,K+-ATPase as the Target Enzyme for Organic and Inorganic Compounds

Vasić

Momić

Petković

et al. 2008

Sensors

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This paper gives an overview of the literature data concerning specific and non specific inhibitors of Na+,K+-ATPase receptor. The immobilization approaches developed to improve the rather low time and temperature stability of Na+,K+-ATPase, as well to preserve the enzyme properties were overviewed. The functional immobilization of Na+,K+-ATPase receptor as the target, with preservation of the full functional protein activity and access of various substances to an optimum number of binding sites under controlled conditions in the combination with high sensitive technology for the detection of enzyme activity is the basis for application of this enzyme in medical, pharmaceutical and environmental research.

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“…Rather than competing with the normal substrates for these transporters, it is likely that DDP disables these enzymes by binding to key thiol groups. The ability to bind DDP may underlie the increase in resistance to DDP that is observed after overexpression of some of these enzymes (Kishimoto et al, 2006). It is of substantial interest that DDP-associated nephrotoxicity is accompanied by severe copper deficiency (DeWoskin and Riviere, 1992).…”

Section: Discussionmentioning

confidence: 99%

Transport of Cisplatin by the Copper Efflux Transporter ATP7B

Safaei

Otani²,

Larson³

et al. 2007

Mol Pharmacol

100

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ATP7B is a P-type ATPase that mediates the efflux of copper. Recent studies have demonstrated that ATP7B regulates the cellular efflux of cisplatin (DDP) and controls sensitivity to the cytotoxic effects of this drug. To determine whether DDP is a substrate for ATP7B, DDP transport was assayed in vesicles isolated from Sf9 cells infected with a baculovirus that expressed either the wild-type ATP7B or a mutant ATP7B that was unable to transport copper as a result of conversion of the transmembrane metal binding CPC motif to CPA. Only the wild-type ATP7B-expressing vesicles exhibited copper-dependent ATPase activity, copper-induced acyl-phosphate formation, and ATP-dependent transport of copper. The amount of DDP that became bound was higher for vesicles expressing either type of ATP7B than for those not expressing either form of ATP7B, but only the vesicles expressing wild-type ATP7B mediated ATP-dependent accumulation of the drug. At pH 4.6, the vesicles expressing the wild-type ATP7B exhibited ATPdependent accumulation of DDP with an apparent K m of 1.2 Ϯ 0.5 (S.E.M.) M and V max of 0.03 Ϯ 0.002 (S.E.M.) nmol/mg of protein/min. DDP also induced the acyl-phosphorylation of ATP7B but at a much slower rate than copper. Copper and DDP each inhibited the ATP-dependent transport of the other. These results establish that DDP is a substrate for ATP7B but is transported at a much slower rate than copper.

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Role of Na+, K+-ATPase α1 subunit in the intracellular accumulation of cisplatin

Cited by 39 publications

References 23 publications

Cisplatin increases urinary sodium excretion in rats: gender-related differences

Cisplatin increases urinary sodium excretion in rats: gender-related differences

Na+,K+-ATPase as the Target Enzyme for Organic and Inorganic Compounds

Transport of Cisplatin by the Copper Efflux Transporter ATP7B

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