Proteasome subunit and opioid receptor gene expression down-regulation induced by paraquat and maneb in human neuroblastoma SH-SY5Y cells.

Abstract

Paraquat (PQ) and maneb (MB) are able to induce neurotoxic effects by promoting α-synuclein (α-syn) aggregates and altering tyrosine hydroxylase (TH), thus increasing the risk of Parkinson's disease (PD). These pesticides promote neurotoxic effects also by affecting proteasome function that normally regulate protein turnover. We investigated the effects of the two pesticides exposure on multiple targets involved in PD, using SH-SY5Y cells. First, we evaluated TH and α-syn protein levels following PQ and MB cell exposure and a significant increase of these protein levels was observed. Subsequently, since a relationship between ubiquitin/proteasome and opioid receptors has been proposed, the effects of pesticides on their gene expression have been investigated. A decrease of β1 and Rpt3 proteasome subunit mRNA levels, together with the μ and δ opioid receptor down-regulation, was detected. The reported alterations, here simultaneously observed, help to clarify the involvement of multiple biological markers implicated in PD, often separately evaluated.