Srivastava S K, Hu X, Xia H, Pal A, Guo J, Orchard J L, Singh S V
Cancer Research Laboratory, Mercy Cancer Institute, Mercy Hospital of Pittsburgh, PA 15219, USA.
FEBS Lett. 1999 Feb 26;445(2-3):291-4. doi: 10.1016/s0014-5793(99)00140-4.
The present study reports gender related differences in ATP-dependent transport of dinitrophenyl-glutathione (GSH) conjugate (DNP-SG), a model GSH xenobiotic conjugate, across murine canalicular liver plasma membrane (cLPM). ATP-dependent transport of DNP-SG across female A/J mouse cLPM was mediated by two components, a high-affinity and a low-affinity component, with corresponding Km of 18 microM (Vmax 0.02 nmol/min.mg) and 500 microM (Vmax 0.23 nmol/min.mg), respectively. On the other hand, only one component for the ATP-dependent transport of DNP-SG was observed in male mouse cLPM (K(m) 130 microM; Vmax 0.18 nmol/min.mg). Moreover, the rate of ATP-dependent transport of DNP-SG was markedly higher in the cLPM fraction of male mouse compared with that of the female. Presence of two transport components in female mouse cLPM, but only one system in the cLPM fraction of male mouse, was confirmed by measuring DNP-SG mediated stimulation of ATP hydrolysis (DNP-SG ATPase activity). To the best of our knowledge, the present study is the first report on gender related differences in ATP-dependent murine canalicular transport of GSH conjugates.
本研究报告了二硝基苯基谷胱甘肽（GSH）结合物（DNP-SG，一种典型的GSH外源性结合物）跨小鼠肝小管质膜（cLPM）的ATP依赖性转运中的性别相关差异。DNP-SG跨雌性A/J小鼠cLPM的ATP依赖性转运由两个成分介导，一个高亲和力成分和一个低亲和力成分，其相应的Km分别为18 microM（Vmax 0.02 nmol/min.mg）和500 microM（Vmax 0.23 nmol/min.mg）。另一方面，在雄性小鼠cLPM中仅观察到DNP-SG的ATP依赖性转运的一个成分（K(m) 130 microM；Vmax 0.18 nmol/min.mg）。此外，雄性小鼠cLPM组分中DNP-SG的ATP依赖性转运速率明显高于雌性。通过测量DNP-SG介导的ATP水解刺激（DNP-SG ATP酶活性）证实了雌性小鼠cLPM中存在两个转运成分，而雄性小鼠cLPM组分中只有一个系统。据我们所知，本研究是关于GSH结合物的ATP依赖性小鼠肝小管转运中性别相关差异的首次报道。
