engleski

Neuropathy target esterase-related enzyme in human muscle cells

Neuropathy target esterase-related enzyme (NRE) is a trans-membrane serine esterase linked to the ER. It has been identified as a member of the patatin domain-containing enzymes family (PNPLA) and has been detected in many human tissues. However, little is known about its role and importance in the organism. Scarce findings suggest NRE involvement in energy metabolism and phospholipid homeostasis. NRE has a high homology to the neuronal neuropathy target esterase (NTE, PNPLA6) originally identified as a target enzyme for highly toxic organophosphorus (OP) compounds (pesticides, nerve warfare agents) that cause a delayed paralyzing syndrome with degeneration of nerve axons. High NRE – NTE homology suggests that NRE might also be a target of OP compounds which implies NRE involvement in OP caused pathological conditions including poorly defined intermediate-myopathy syndrome. In order to elucidate NRE involvement in such state we first explored its expression and physiological role in the human muscle cells. NRE expression was followed by detecting its mRNA level, protein level and its esterase activity under various conditions mimicking the in vivo states to which muscle might respond at the NRE level. These conditions included changed nutrients, exposure to hypoxia and hormones and also exposure to OPs. These conditions are actually an experimental model for the in vivo states such as regeneration, hypoxia, fasting or myopathy. We also followed myoblasts response to the NRE mRNA silencing with the goal to find out if such treatment affects myoblast membrane integrity.

PNPLA family; OP; physiological role; esterase activity

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