PGE1 triggers Nrf2/HO-1 signal pathway to resist hemin-induced toxicity in mouse cortical neurons.

BACKGROUND

Prostaglandin E1 (PGE1) exerts various pharmacological effects such as membrane stabilization, anti-inflammatory functions, vasodilation, and platelet aggregation inhibition. We have previously demonstrated that PGE1 has a beneficial impact on patients suffering from intracerebral hemorrhage (ICH). The related mechanism underlying PGE1's beneficial effect on ICH treatment needs further exploration.

METHODS

The present study elucidates the mechanism of PGE1 on ICH treatment using a neuronal apoptosis model . The mouse primary cortical neurons were pretreated with different concentrations of PGE1, followed by the treatment with hemin, the main catabolite in whole blood, to mimic the clinical ICH.

RESULTS

Comparing with the vehicle-treated group, PGE1 prevented cultured cortical neurons from the accumulation of inhibited intracellular levels of reactive oxygen species (ROS), amelioration of mitochondrial membrane potential, and hemin-induced apoptosis. The reduction of ROS and apoptosis were associated with the up-regulation of Heme oxygenase-1 (HO-1) expression. Knockdown of nuclear transcription factor erythroid 2-related factor (Nrf2) by siRNA attenuated the upregulation of HO-1 as well as the protective effect of PGE1.

CONCLUSIONS

Our work suggests that the Nrf2/HO-1 molecular pathway may play a crucial role in treating ICH patients with PGE1 and may represent novel molecular targets, resulting in discovering new drugs for ICH treatment.