engleski

The Effects of Organophosphates in the Early Stages of Human Muscle Regeneration

Myopathy is frequent at the organophosphate (OP) poisoning. Skeletal muscle responds to it by activating regeneration process which starts from the dormant mononuclear satellite cells located under the basal lamina of the adult muscle fibers. The step which decisively determines the mass of regenerated muscle is proliferation of myoblasts, which develop from the activated satellite cells. Our investigations were therefore focused on the effects of OPs on these early myogenic precursors. The OP effects – diisopropyl-phosphorofluoridate (DFP) was used in most of our experiments - were studied in the in vitro model which reproduces all stages of human muscle regeneration. We found that DFP decreases IL-6 release from myoblasts which might directly impair muscle regeneration since IL-6 promotes myoblast proliferation. A cellular response to stress indicated by increased level of heat shock proteins was observed in DFP-exposed myoblasts. Hypoxia, which can be severe in OP poisoning, led to the marked increase of hypoxia-inducible factor-1α expression in myoblasts. A neuropathy target esterase – related enzyme (NRE) was identified in our muscle cultures ; its inhibition by DFP opens new explanations of the OP effects in the skeletal muscle. However, de novo AChE synthesis in human myoblasts was not altered by DFP. OPs therefore interact with various systems in human myoblasts which might have important consequences on muscle regeneration.

human muscle, muscle regeneration, myoblasts, diisopropylphosphorofluoridate, HI-6, heat shock proteins, hypoxia-inducible factor-1, acetylcholinesterase, neuropathy target esterase – related enzyme

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