期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 203, 期 1, 页码 144-148出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2012.09.015
关键词
Acetylcholinesterase; Antidotes; Tabun; Cytokines; Heat shock proteins; Myopathy
资金
- Ministry of Science, Education and Sports of the Republic of Croatia [022-0222148-2889]
- Slovenia Research Agency
- Slovene Human Resources Development and Scholarship Fund grant [111013-18/2011]
- Croatian-Slovenian bilateral grant [BI-HR/07-08-020]
- EMBO [ASTF 178-2011]
Organophosphorus compounds (OPs) and oximes may interfere with other molecules than AChE in the living systems, affecting in this way various cellular processes and underlying mechanisms. These non-cholinergic effects may contribute to the clinical status in OP poisoning and therefore deserve equal scientific attention. Here, we investigated the effects of tabun and oxime K048 on the processes known to be involved in muscle response to the environmental factors, like IL-6 release and the regulation of the heat shock proteins (HSPs). While IL-6 stimulates muscle regeneration, which follows well known OP-induced myopathy, HSPs have cytoprotective effect against various stress factors including xenobiotics. All our experiments were carried out on cultured human myoblasts, as the precursors of muscle regeneration. We found unchanged AChE mRNA level after tabun/K048 treatment meaning that tabun and K048 did not interfere with the transcription or stability of this mRNA in the time period tested, even if AChE catalytic activity was significantly affected. On the other hand, after myoblast exposure to tabun, we observed significant changes in the protein levels of HSP 27 and in the secretion of IL-6. Namely, secretion of IL-6 decreased to 53% and the level of HSP 27 increased by 34% compared to the control level. Both effects were attenuated if myoblasts were pretreated with oxime K048, but not if they were treated with K048 after exposure to tabun. The molecular mechanism underlying these effects remains to be elucidated. However, it seems that these effects could be associated with OPs and oximes as a specific group of compounds rather than as a specific compound itself. Overall, the effects of OPs and oximes demonstrated here might play an important role in muscle regeneration which importantly determines the final outcome of OP myotoxicity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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