Proteasome inhibition by MG-132 protects against deltamethrin-induced apoptosis in rat hippocampus

Deltamethrin (DM), a type II synthetic pyrethroid insecticide, is widely used in agriculture and home pest control. The evaluation of their toxic effects is of major concern to public health. However, the molecular mechanism of DM-induced neurodegenerative disease is still far from clear. This study was designed to investigate the potential role of ubiquitin proteasome system (UPS) in DM-induced neurotoxicity where the proteasome inhibitor MG-132 could mitigate the neurotoxic effects.

Male Sprague-Dawley rats were divided into two batches. The first batch of rats was administrated with a single dose of DM (12.5 mg/kg) by intraperitoneal injections (i.p.) and the animals were then euthanized at 5, 24, and 48 h post injection. The second batch was treated as follow: control group, DM (12.5 mg/kg) groups for 24 h, MG-132 (0.5 mg/kg, i.p.) 2 h plus DM 24 h group, and MG-132 alone group. Ubiqutinatied proteins, DNA damage and apoptosis were investigated.

DM treatment induced the ubiquitinated proteins expression with the peaks at 5 h. Moreover, DM increased DNA damage, early apoptotic rate, the expression level of Cleaved Caspase-3, caspase-3 activity and decreased the expression level of Bcl-2 at DM 24 h group. Compared to DM 24 h group, MG-132 pretreatment significantly down-regulated ubiquitinated proteins, lowered the DNA damage and apoptosis by decreasing Caspase-3 and increasing Bcl-2 expression.

These results indicate that MG-132 effectively alleviates DM-induced DNA damage and apoptosis by inhibiting ubiquitinated proteins. UPS may play a role in DM-induced neurodegenerative disorders.