Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin NT, Hong Kong, China.
Neurotox Res. 2010 Aug;18(2):161-72. doi: 10.1007/s12640-009-9122-1. Epub 2009 Oct 23.
The aim was to study the mechanism of neuronal toxicity, the cellular pathway, and the glial cell reactions induced by trichosanthin (TCS), a type I ribosome-inactivating protein (RIP). Ricin A chain (RTA) was included for comparison. TCS, RTA, and fluorescein isothiocyanate (FITC)-labeled TCS and RTA were separately injected into rat eyes. Saline or pure FITC was used as the control. Electron microscopy, confocal microscopy, and lectin and immunohistochemical staining were used to study the neurotoxic mechanism. TCS mainly induced apoptosis by causing degeneration of the mitochondria. TCS was able to enter the Müller and pigment cells. It caused a change in cell number of the following types of glial cells: a decrease in Müller cells, an increase in astrocytes, and little change in microglia. In contrast, RTA mainly induced necrosis and entered vascular endothelial cells. Astrocyte and microglia reactions were stronger in the RTA-treated retinas than those in the TCS-treated retinas. In conclusion, TCS appears to selectively enter and destroy Müller and pigment epithelia cells, which subsequently induce the death of photoreceptors. Degeneration of mitochondria is involved in the pathways of apoptosis of the photoreceptors caused by TCS. In sharp contrast, RTA can enter vascular endothelial cells and damage the vascular endothelium, resulting in retinitis and necrosis.
目的是研究天花粉蛋白（TCS）作为一种 I 型核糖体失活蛋白（RIP）诱导的神经元毒性、细胞途径和神经胶质细胞反应的机制。蓖麻毒素 A 链（RTA）也包括在内作为比较。TCS、RTA 和异硫氰酸荧光素（FITC）标记的 TCS 和 RTA 分别注射到大鼠眼睛中。盐水或纯 FITC 用作对照。电子显微镜、共聚焦显微镜以及凝集素和免疫组织化学染色用于研究神经毒性机制。TCS 主要通过引起线粒体变性来诱导细胞凋亡。TCS 能够进入 Müller 和色素细胞。它导致以下类型的神经胶质细胞数量发生变化：Müller 细胞减少，星形胶质细胞增加，小胶质细胞变化不大。相比之下，RTA 主要诱导坏死并进入血管内皮细胞。RTA 处理的视网膜中星形胶质细胞和小胶质细胞的反应比 TCS 处理的视网膜更强。总之，TCS 似乎选择性地进入并破坏 Müller 和色素上皮细胞，随后诱导光感受器死亡。线粒体的退化涉及 TCS 诱导的光感受器细胞凋亡途径。相比之下，RTA 可以进入血管内皮细胞并损伤血管内皮，导致视网膜炎和坏死。
