Naslov
Organophosphorus compound poisoning: from benchtop to clinic and back

Autori
Katalinić, Maja ; Miš, Katarina ; Gros, Katarina ; Zorbaz, Tamara ; Zandona, Antonio ; Matkovič, Urška ; Pavičić, Ivan ; Marjanović, Ana Marija ; Kovarik, Zrinka ; Grubič, Zoran ; Pirkmajer, Sergej ; Marš, Tomaž

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Skeletal muscle research - from cell to human 2017, Symposium and Workshop, Book of Abstracts / Kacin, Alan ; Pirkmajer, Sergej ; Podbregar, Matej - Ljubljana : Faculty of medicine and Faculty of Health Sciences, University of Ljubljana, Slovenija, 2017, 60-61

ISBN
978-961-267-123-5

Skup
Symposium and Workshop: Skeletal muscle research - from cell to human 2017

Mjesto i datum
Ljubljana, Slovenija, 28.05.2017. - 30.05.2017

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
muscle cells, neuronal cells, AChE, citotoxicity

Sažetak
From the discovery of their potential at the beginning of the 20th century up until now, organophosphates (OPs) have found various uses. One of their main applications is pest control, but due to species non-selectivity intentional or unintentional human poisoning became a great problem. Furthermore, some OPs have been developed to be used as nerve warfare agents (soman, sarin, tabun, VX). Even though this is prohibited by international conventions, there is still a realistic threat of their misuse in terroristic attacks as we witnessed in recent events worldwide. Despite the fact that we have known that acetylcholinesterase (AChE) is the main target of OPs action for decades, the development of a more effective treatment for OP poisoning than the one currently used still presents a challenge for researchers in the field. Namely, clinical data point to symptoms such as myopathies and neuropathies related to other mechanisms of OP action than the inhibition of AChE per se. To understand what drives such effects, we investigated the influence of OPs and oxime reactivators on muscle and neuronal cells as the primary site of their action. In human myoblasts, the early precursors of regenerating muscle fibres, we found significant changes in HSP 27 protein levels and in the secretion of IL-6 upon OP exposure. These effects were attenuated when myoblasts were pretreated but not if they were treated with oxime post OP. Furthermore, we identified the presence of a novel serine esterase (NRE) sensitive to OPs in muscle cells. Since NRE plays a role in phospholipid homeostasis, its inhibition perhaps leads to changes in cell lipid content and in that way stimulates myopathies. On the other hand, several of the tested oximes induced a significant cytotoxic effect in neuronal cells. The cells seemed to be more sensitive to the uncharged oximes carrying several aromatic moieties than to the charged ones with the presence of quaternary nitrogen. Though the exact mechanism of observed chemosensitivity needs to be elucidated, preliminary tests indicate that the effect is governed by apoptosis. Taken together, the studies indicate that there is much more to OP poisoning and subsequent therapy than visible at first glance but it will certainly be a starting point in the development of more effective treatment in the future. Research Funding and Acknowledgements This work was supported by the by the Ministry of Science, Education and Sports of the Republic of Croatia (Grant no. 022-02221482889), the Croatian Science Foundation (Grant no. 4307), Slovenia Research Agency grant (Research programme P3-0043), Slovene Human Resources Development and Scholarship Fund grant (111013-18/2011), Croatian-Slovenian bilateral grants (2007-2008, 2014-2015), the EMBO short term fellowship (ASTF 178-2011) and the Fellowship of the Slovene Human Resources, Development and Scholarship Fund, Republic of Slovenia to M. Katalinić (11013-18/2011-5).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA