Department of Molecular Pharmacology, Technion-Israel Institute of Technology, Ephron Street, P.O. Box 9649, Bat-Galim, Haifa 31096, Israel.
Curr Mol Med. 2012 May;12(4):494-501. doi: 10.2174/1566524011207040494.
By exposing cells of the U118MG glioblastoma cell line to protoporphyrin IX (PPIX) in culture, we found that the 18 kDa mitochondrial translocator protein (TSPO) prevents intracellular accumulation of PPIX. In particular, TSPO knockdown by stable transfection of TSPO silencing siRNA vectors into U118MG cells leads to mitochondrial PPIX accumulation. In combination with light exposure, the PPIX accumulation led to cell death of the TSPO knockdown cells. In the sham control cells (stable transfection of scrambled siRNA vectors), TSPO expression remained high and no PPIX accumulation was observed. The prevention of PPIX accumulation by TSPO was not due to conversion of PPIX to heme in the sham control cells. Similar to TSPO knockdown, the reactive oxygen species (ROS) scavenger glutathione (GSH) also enhanced PPIX accumulation. This suggests that that ROS generation as modulated by TSPO activation may present a mechanism to prevent accumulation of PPIX.
通过将 U118MG 神经胶质瘤细胞系的细胞暴露于培养中的原卟啉 IX（PPIX）中，我们发现 18kDa 线粒体转位蛋白（TSPO）可防止 PPIX 在细胞内积累。具体来说，通过将 TSPO 沉默 siRNA 载体稳定转染到 U118MG 细胞中，可使 TSPO 敲低，从而导致线粒体 PPIX 积累。与光照结合，PPIX 的积累导致 TSPO 敲低细胞死亡。在假对照细胞（稳定转染 scrambled siRNA 载体）中，TSPO 表达仍然很高，并且没有观察到 PPIX 积累。TSPO 阻止 PPIX 积累并不是由于在假对照细胞中 PPIX 转化为血红素所致。与 TSPO 敲低相似，活性氧（ROS）清除剂谷胱甘肽（GSH）也增强了 PPIX 的积累。这表明 TSPO 激活调节的 ROS 生成可能提供了一种防止 PPIX 积累的机制。
