Changes in mRNA expression levels of synaptic- and target tissue-specific proteins after organophosphate exposure.
We examined the effects of organophosphate exposure on mRNA expression levels of synaptic- and target tissue-specific proteins in rats. We treated rats with a single dose of Disulfoton (O,O-diethyl S-2-ethylthioethyl phosphorodithioate) and used quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure the time course of changes in the levels of mRNAs encoding acetylcholinesterase (AChE), nicotinic acetylcholine receptor (nAChR), beta-enolase (MSE), and gamma-enolase (NSE) in soleus muscles and sciatic nerves. The expression levels of synaptic genes encoding AChE in both tissues were significantly decreased, with a nadir at 12h after the administration, and this down-regulation lasted for up to 30 days after administration. Similarly, the level of nAChR mRNA in soleus muscle also decreased, with a nadir at 48 h after administration and a return to 95% of that of the control levels by 30 days after administration. These results indicate that administration of organophosphate can decrease AChE and nAChR expression in the neuromuscular junction, and are suggestive of multiple mechanisms of down-regulation of both AChE and nAChR, some of which might involve alterations at the transcriptional level. The transcript level of the target tissue-specific gene encoding MSE in soleus muscle was slightly decreased, with a nadir at 48 h after administration, and was still lower than that of the control level after 30 days. In contrast, the level of the NSE transcript in sciatic nerve significantly increased within 2 h, and this up-regulation was sustained until 30 days after administration. Although the functions of either of these enolases are not completely established, up-regulation of NSE mRNA may be a marker for the nervous system abnormality following organophosphate exposure. All of these phenomena may contribute to the long-lasting neurotoxic effects observed after developmental exposure to organophosphates.
Matsuda
H
H
Department of Legal Medicine, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan.
Seo
Y
Y
Kakizaki
E
E
Takahama
K
K