Mechanism of the specific neuronal toxicity of a type I ribosome-inactivating protein, trichosanthin.
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.
Sha
Ou
O
Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin NT, Hong Kong, China. shaou@cuhk.edu.hk
Yew
David Tai-Wai
DT
Cho
Eric Yu-Pang
EY
Ng
Tzi-Bun
TB
Yuan
Lin
L
Kwong
Wing-Hang
WH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count / Q000706:statistics & numerical data; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D056965:Injections, Intraocular; D008928:Mitochondria / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D037121:Plant Lectins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000633:toxicity*; D012276:Ricin / Q000633:toxicity; D015978:Trichosanthin / Q000008:administration & dosage / Q000633:toxicity*
D005904:Glial Fibrillary Acidic Protein; C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D054789:Ribosome Inactivating Proteins, Type 1; D015978:Trichosanthin; D012276:Ricin