J Korean Neurol Assoc.  2016 May;34(2):116-123. 10.17340/jkna.2016.2.5.

Inhibitory Effect of Apocynin on Proteasome Inhibition-Induced Apoptosis in Differentiated PC12 Cells

• Kang JH
• Han SW
• Han JH
• Kim DE
• Lee CS

• KMID: 2163256
• DOI: http://doi.org/10.17340/jkna.2016.2.5

Abstract

BACKGROUND
The dysfunction of the proteasome system has been implicated in neuronal degeneration. Apocynin, a specific inhibitor for nicotinamide adenine dinucleotide phosphate oxidase, has anti-inflammatory and anti-oxidant effects. However, the effect of apocynin on the neuronal cell death induced by proteasome inhibition has not been studied.
METHODS
Using differentiated PC12 cells, in the respect of cell death process the suppressive effect of apocynin on the proteasome inhibition-mediated apoptosis was examined.
RESULTS
The proteasome inhibitors MG132 and MG115 induced a decrease in Bid and Bcl-2 protein levels, an increase in Bax and p53 levels, mitochondrial depolarization, efflux of cytochrome c into cytosol and increase in caspases (-8, -9 and -3) activities. Treatment with apocynin attenuated the proteasome inhibitor-induced changes in the apoptosis-related protein levels, formation of reactive oxygen species, glutathione (GSH) depletion and cell death.
CONCLUSIONS
Apocynin may attenuate the proteasome inhibitor-mediated apoptosis in differentiated PC12 cells by inhibiting the activation of the mitochondria-mediated pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of apocynin appears to be attributed to inhibition of the production of reactive oxygen species and the depletion of cellular GSH contents.

Keyword

Apocynin; Proteasome inhibition; PC12 cells; Apoptosis-related proteins; Protection

MeSH Terms

Animals
Antioxidants
Apoptosis*
Caspases
Cell Death
Cytochromes c
Cytosol
Glutathione
NADP
Neurons
Oxidoreductases
PC12 Cells*
Proteasome Endopeptidase Complex*
Proteasome Inhibitors
Reactive Oxygen Species
Antioxidants
Caspases
Cytochromes c
Glutathione
NADP
Oxidoreductases
Proteasome Endopeptidase Complex
Proteasome Inhibitors
Reactive Oxygen Species