The proteasomal dysfunction and mitochondrial impairment has been implicated in neuronal degeneration.
Taxifolin has
antioxidant and anti-inflammatory effects. However, the effect of
taxifolin on the neuronal cell death induced by
proteasome inhibition has not been studied. Therefore, in the respect of cell death process, we assessed the effect of
taxifolin on the
proteasome inhibition-induced apoptosis in neuronal cell injury using differentiated PC12 cells. The
proteasome inhibitors MG132 and
MG115 induced a decrease in Bid, Bcl-2, and
survivin protein levels, an increase in Bax, loss of the mitochondrial transmembrane potential,
cytochrome c release, activation of caspases(-8, -9 and -3), an increase in the
tumor suppressor p53 levels and cleavage of PARP-1. The addition of
taxifolin attenuated the
proteasome inhibitor-induced changes in the apoptosis-related
protein levels, formation of
reactive oxygen species, depletion and oxidation of GSH, formations of
malondialdehyde and carbonyls, and cell death. The results show that
taxifolin may attenuate the
proteasome inhibitor-induced apoptosis in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of
taxifolin appears to be attributed to its inhibitory effect on the formation of
reactive oxygen species, and depletion and oxidation of GSH.