Zalewski P D, Forbes I J, Seamark R F, Borlinghaus R, Betts W H, Lincoln S F, Ward A D
Department of Medicine, University of Adelaide, Queen Elizabeth Hospital, Woodville, Australia.
Chem Biol. 1994 Nov;1(3):153-61. doi: 10.1016/1074-5521(94)90005-1.
The transition metal Zn(II) is thought to regulate cell and tissue growth by enhancing mitosis (cell proliferation) and suppressing the counterbalancing process of apoptosis (gene-directed cell death). To investigate the role of Zn(II) further, we have used a UV-excitable Zn(II)-specific fluorophore, Zinquin. The ester group of Zinquin is hydrolyzed by living cells, ensuring its intracellular retention; this allows the visualization and measurement of free or loosely-bound (labile) intracellular Zn(II) by fluorescence video image analysis or fluorimetric spectroscopy.
Here we show that in cells undergoing early events of apoptosis, induced spontaneously or by diverse agents, there is a substantial increase in their Zinquin-detectable Zn(II). This increase occurred in the absence of exogenous Zn(II) and before changes in membrane permeability, consistent with a release of Zn(II) from intracellular stores or metalloproteins rather than enhanced uptake from the medium. We propose that there is a major redistribution of Zn(II) during the induction of apoptosis, which may influence or precipitate some of the later biochemical and morphological changes.
The phenomenon of Zn(II) mobilization, revealed by Zinquin, presents a new element in the process of apoptosis for investigation and may permit rapid and sensitive identification of apoptotic cells, particularly in those tissues where their frequency is low.
过渡金属锌离子（Zn(II)）被认为可通过促进有丝分裂（细胞增殖）和抑制细胞凋亡（基因导向的细胞死亡）这一平衡过程来调节细胞和组织生长。为进一步研究Zn(II)的作用，我们使用了一种紫外线可激发的Zn(II)特异性荧光团锌喹啉（Zinquin）。锌喹啉的酯基被活细胞水解，确保其在细胞内保留；这使得通过荧光视频图像分析或荧光光谱法能够可视化和测量游离或松散结合（不稳定）的细胞内Zn(II)。
我们在此表明，在自发或由多种因素诱导发生早期凋亡事件的细胞中，其锌喹啉可检测到的Zn(II)显著增加。这种增加在没有外源性Zn(II)的情况下且在膜通透性改变之前就已发生，这与Zn(II)从细胞内储存库或金属蛋白中释放出来而非从培养基中摄取增加一致。我们提出，在细胞凋亡诱导过程中存在Zn(II)的主要重新分布，这可能会影响或促成一些后期的生化和形态学变化。
锌喹啉揭示的Zn(II)动员现象是细胞凋亡过程中一个有待研究的新因素，并且可能允许快速、灵敏地鉴定凋亡细胞，尤其是在那些凋亡细胞频率较低的组织中。
