Naslov
The effects of organophosphorous compounds and their protecting agents on stress markers in cultered human muscle

Autori
Marš, Tomaž ; Miš, Katarina ; Pirkmajer, Sergej ; Pegan, Katarina ; Grubič, Zoran ; Bosak, Anita ; Katalinić, Maja ; Kovarik, Zrinka

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

Izvornik
10th International Meeting on Cholinesterases, Šibenik, Croatia, Programme and Abstracts / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2009, 116-116

ISBN
978-953-95551-3-7

Skup
10th International Meeting on Cholinesterases

Mjesto i datum
Šibenik, Hrvatska, 20.09.2009. - 25.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Nerve agent; Oximes; Cholinesterases; Acetylcholinesterase; Butyrylcholinesterase; Heat shock protein; Interleukin

Sažetak
Toxic effects of organophosphorous (OPs) compounds are primarily the result of acetylcholinesterase (AChE) inhibition. However, there is evidence that AChE and other cholinesterases (ChEs) are not the only targets of OPs and that various intracellular mechanisms are modified due to direct or indirect actions of OPs. These effects can modify clinical condition and the final outcome of OP intoxications and therefore deserve scientific attention. Typically met upon the OP poisoning are myopathies, the final outcome of which depends also on the muscle regeneration, which is triggered in the muscle after its damage. OPs can potentially interfere with muscle regeneration at the various levels including the interference with stress response in the precursors of muscle regeneration. As previously proposed they can exert this effect either by changing conformation of ChE protein affecting in this way its non-cholinergic function and/or by direct OP binding to some yet unidentified non-cholinergic molecules. Here we tested the hypothesis that these OP effects might also be prevented by oxime agents applied either prior or after OP exposure. Our investigations were carried out on cultured human myoblasts as these cells are the key contributors to muscle regeneration. We first tested whether pre- and post-treatment with the oxime agent K048 influences the expression and activity of acetylcholinesterase (AChE) in the tabun-treated myoblasts. Then we studied the effects of tabun and K048 on the selected markers of stress response in particular on the interleukin-6 (IL-6) secretion and heat shock protein (HSP) 27 and 70 expression. We found that exposure of human myoblasts to tabun in combination with K048 applied prior or after exposure to tabun did not interfere with AChE mRNA expression although the level of AChE activity was significantly affected. However, in myoblasts exposed to tabun constitutive IL-6 secretion was inhibited and increased level of HSP 27 was detected. This effect was prevented by pretreatment of myoblasts with K048 but not by applying K048 after tabun exposure. Our results suggest that pretreatment with protective agents might be beneficial also in a sense that they alleviate myopathic effect of OP poisoning since IL-6 stimulates myoblast proliferation. The role of oxime pretreatment at the level of HSPs remains to be elucidated.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA