The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae.
作者： Xinjian Lin , Tsuyoshi Okuda , Alison Holzer , Stephen B. Howell
关键词: Carboplatin 、 Platinum 、 Chemistry 、 Biochemistry 、 Cytotoxic T cell 、 Copper 、 Saccharomyces cerevisiae 、 Transporter 、 Oxaliplatin 、 Cisplatin
摘要: Resistance to cisplatin (DDP) is often accompanied by impaired accumulation in mammalian cells. The mechanism of DDP unknown, but copper uptake diminished as well. We investigated the ability transporter CTR1 control Saccharomyces cerevisiae . Parallel studies and cellular pharmacokinetics were carried out using an isogenic pair wild-type ctr1 knockout S. strains. Both platinum increased linearly a function time drug concentration parental Deletion resulted 16-fold reduction 8-fold measured at 1 h. CTR1-deficient cells accumulated 2.3-fold ( p < 0.05) less their DNA 1.9-fold more resistant cytotoxic effect than CTR1-replete kinetics similar those DDP. Based on measurements h, K m for influx was 128.8 μM, V max 169.5 ng/mg protein/min; DDP, 140.2 μM 76.9 protein/min. blocked into not -deficient also demonstrated analogs carboplatin, oxaliplatin, ZD0473 [ cis -amminedichloro(2-methylpyridine) (II)]. These results indicate that markedly influences all clinically used platinum-containing drugs suggest this may transport
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