Hu Jin-Shan, Li Ying-Bin, Wang Jiong-Wei, Sun Lin, Zhang Guo-Jiang
School of Science, Hebei University of Technology, Tianjin, 300130, People's Republic of China.
J Membr Biol. 2007 Jan;215(1):27-35. doi: 10.1007/s00232-007-9002-7. Epub 2007 May 18.
Lysosomal destabilization is critical for the organelle and living cells. Phospholipase A(2 )(PLA(2)) was shown to be able to destabilize lysosomes under some conditions. By what mechanism the enzyme affects lysosomal stability is not fully studied. In this study, we investigated the effects of lysophosphatidylcholine (lysoPC), a PLA(2)-produced lipid metabolite, on lysosomal ion permeability, osmotic sensitivity and stability. By measuring lysosomal beta-hexosaminidase free activity, membrane potential, proton leakage and their enzyme latency loss in hypotonic sucrose medium, we established that lysoPC could increase the lysosomal permeability to both potassium ions and protons and enhance lysosomal osmotic sensitivity. These changes in lysosomal membrane properties promoted entry of potassium ions into lysosomes via K(+)/H(+) exchange. The resultant osmotic imbalance across the membranes led to losses of lysosomal integrity. The enhancement of lysosomal osmotic sensitivity caused the lysosomes to become more liable to destabilization in osmotic shock. These results suggest that lysoPC may play a key role in PLA(2)-induced lysosomal destabilization.
溶酶体的不稳定对细胞器和活细胞至关重要。磷脂酶A2（PLA2）已被证明在某些条件下能够使溶酶体不稳定。该酶影响溶酶体稳定性的机制尚未得到充分研究。在本研究中，我们研究了溶血磷脂酰胆碱（lysoPC），一种PLA2产生的脂质代谢产物，对溶酶体离子通透性、渗透敏感性和稳定性的影响。通过测量溶酶体β-己糖胺酶的游离活性、膜电位、质子泄漏以及它们在低渗蔗糖培养基中的酶潜伏性丧失，我们确定lysoPC可以增加溶酶体对钾离子和质子的通透性，并增强溶酶体的渗透敏感性。溶酶体膜性质的这些变化促进了钾离子通过K(+)/H(+)交换进入溶酶体。由此导致的跨膜渗透失衡导致溶酶体完整性丧失。溶酶体渗透敏感性的增强使溶酶体在渗透休克中更容易不稳定。这些结果表明，lysoPC可能在PLA2诱导的溶酶体不稳定中起关键作用。
