Rosen H, Glukmann V, Feldmann T, Fridman E, Lichtstein D
The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute of Microbiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Cell Mol Biol (Noisy-le-grand). 2006 Dec 30;52(8):78-86.
Cardiac steroids (CS) are specific inhibitors of Na+, K+-ATPase activity. Although the presence of CS-like compounds in animal tissues has been established, their physiological role is not clear. In a previous study we showed that in pulse-chase membrane-labeling experiments, long term (hours) interaction of CS at physiological concentrations (nM) with Na+, K+-ATPase, caused changes in endocytosed membrane traffic in human NT2 cells. This was associated with the accumulation of large vesicles adjacent to the nucleus. For this sequence of events to function in the physiological setting, however, CS would be expected to modify membrane traffic upon short term (min) exposure and membrane labeling. We now demonstrate that CS affects membrane traffic also following a short exposure. This was reflected by the CS-induced accumulation of FM1-43 and transferrin in the cells, as well as by changes in their colocalization with Na+, K+-ATPase. We also show that the CS-induced changes in membrane traffic following up to 2 hrs exposure are reversible, whereas longer treatment induces irreversible effects. Based on these observations, we propose that endogenous CS-like compounds are physiological regulators of the recycling of endocytosed membrane proteins and cargo in neuronal cells, and may affect basic mechanisms such as neurotransmitter release and reuptake.
强心甾类化合物（CS）是Na +，K + -ATP酶活性的特异性抑制剂。尽管已确定动物组织中存在类CS化合物，但其生理作用尚不清楚。在先前的一项研究中，我们表明，在脉冲追踪膜标记实验中，生理浓度（nM）的CS与Na +，K + -ATP酶的长期（数小时）相互作用，导致人NT2细胞内吞膜运输发生变化。这与细胞核附近大囊泡的积累有关。然而，为了使这一系列事件在生理环境中发挥作用，预计CS在短期（分钟）暴露和膜标记后会改变膜运输。我们现在证明，CS在短期暴露后也会影响膜运输。这表现为CS诱导细胞内FM1-43和转铁蛋白的积累，以及它们与Na +，K + -ATP酶共定位的变化。我们还表明，暴露长达2小时后CS诱导的膜运输变化是可逆的，而更长时间的处理会诱导不可逆的影响。基于这些观察结果，我们提出内源性类CS化合物是神经元细胞内吞膜蛋白和货物再循环的生理调节剂，并且可能影响诸如神经递质释放和再摄取等基本机制。
