Zhao Hui-Fang, Wang Xiang, Zhang Guo-Jiang
University of Science and Technology of Beijing, PR China.
FEBS Lett. 2005 Feb 28;579(6):1551-6. doi: 10.1016/j.febslet.2005.01.061.
Lysosomal disintegration is a crucial event for living cells, but mechanisms for the event are still unclear. In this study, we established that the cytosolic extracts could enhance lysosomal osmotic sensitivity and osmotically destabilize the lysosomes. The cytosol also caused the lysosomes to become more swollen in the hypotonic sucrose medium. The results indicate that the cytosol induced an osmotic shock to the lysosomes and an influx of water into the organelle. Since the effects of cytosol on the lysosomes could be abolished by O-tricyclo[5.2.1.0(2,6)]dec-9-yl dithiocarbonate potassium salt (D609), a specific inhibitor of cytosolic phospholipase C (PLC), the PLC might play an important role in the lysosomal osmotic destabilization. The activity of cytosolic PLC and the extent of enzyme latency loss of the cytosol-treated lysosomes exhibited a similar biphasic dependence on the cytosolic Ca2+ concentration. In addition, the cytosol did not osmotically destabilize the lysosomes until the cytosolic calcium ions rose above 100 nM. It suggests that the destabilization effect of cytosol on the lysosomes is Ca(2+)-dependent.
溶酶体解体对活细胞来说是一个关键事件，但其发生机制仍不清楚。在本研究中，我们证实细胞溶质提取物可增强溶酶体的渗透压敏感性，并使溶酶体在渗透压作用下不稳定。细胞溶质还会使溶酶体在低渗蔗糖培养基中变得更加肿胀。结果表明，细胞溶质对溶酶体引发了渗透压休克，并使水流入细胞器。由于胞质磷脂酶C（PLC）的特异性抑制剂O-三环[5.2.1.0(2,6)]癸-9-基二硫代碳酸钾盐（D609）可消除细胞溶质对溶酶体的影响，因此PLC可能在溶酶体渗透压不稳定过程中发挥重要作用。细胞溶质PLC的活性以及经细胞溶质处理的溶酶体酶潜伏性丧失程度对细胞溶质Ca2+浓度表现出相似的双相依赖性。此外，在细胞溶质钙离子浓度升至100 nM以上之前，细胞溶质不会使溶酶体在渗透压作用下不稳定。这表明细胞溶质对溶酶体的不稳定作用是Ca(2+)依赖性的。
