engleski

The effects of organophosphates in the early stages of human skeletal muscle regeneration

Myopathy is a serious consequence of organophosphate (OP) poisoning. Skeletal muscle responds to it by activating a regeneration process that starts with activation of satellite cells. Activated satellite cells differentiate into myoblasts, the proliferation of which decisively determines the mass of regenerated tissues. We investigated OP effects by exposing cultured human myoblasts to diisopropylphosphorofluoridate (DFP). DFP decreased IL-6 secretion, which might impair regeneration by suppressing myoblast proliferation. Increased levels of heat shock proteins in DFP-treated myoblasts indicated activation of the stress response. Hypoxia, which can be severe in OP poisoning, markedly increased the expression of hypoxia-inducible factor-1α without affecting apoptosis. Myoblasts expressed neuropathy target esterase- related enzyme ; its inhibition by DFP opens new explanations into the OP effects in skeletal muscle. However, de novo AChE synthesis in human myoblasts is not altered by DFP. Interactions of OPs with multiple molecular targets in human myoblasts might have important consequences for skeletal muscle regeneration.

human skeletal muscle ; muscle regeneration ; myoblasts ; diisopropylphosphorofluoridate ; heat shock proteins ; hypoxia-inducible factor-1 ; acetylcholinesterase ; neuropathy target esterase-related enzyme ; apoptosis

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