Bis(ethylmaltolato)oxidovanadium (IV) mitigates neuronal apoptosis resulted from amyloid-beta induced endoplasmic reticulum stress through activating peroxisome proliferator-activated receptor γ

Neuronal apoptosis caused by amyloid-beta (A beta) overproduction is one of the most important pathological features in Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress induced by A beta overload plays a critical role in this process. Bis(ethylmaltolato)oxidovanadium (IV) (BEOV), a vanadium compound which had been regarded as peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, was reported to exert an antagonistic effect on ER stress. In this study, we tested whether BEOV could ameliorate the A beta-induced neuronal apoptosis by inhibiting ER stress. It was observed that BEOV treatment ameliorated both tunicamycin-induced and/or A beta-induced ER stress and neurotoxicity in a dose-dependent manner through downgrading ER stress-associated and apoptosis-associated proteins in primary hippocampal neurons. Consistent with in vitro results, BEOV also reduced ER stress and inhibited neuronal apoptosis in hippocampi and cortexes of transgenic AD model mice. Moreover, by adopting GW9662 and salubrinal, the inhibitor of PPAR gamma and hyperphosphorylated eukaryotic translation initiation factor 2 alpha, respectively, we further confirmed that BEOV alleviated A beta-induced ER stress and neuronal apoptosis in primary hippocampal neurons by activating PPAR gamma. Taken together, these results provided scientific evidences to support the concept that BEOV ameliorates A beta-induced ER stress and neuronal apoptosis through activating PPAR gamma.