J Korean Neurol Assoc.  2014 May;32(2):72-81.

Inhibitory Effect of 3,4,5-Tricaffeoylquinic Acid on Parkinsonian Toxin 1-Methyl-4-phenylpyridinium-induced Apoptosis

• Joo JJ
• Kang JH
• Han JH
• Kim DE
• Lee CS

Abstract

BACKGROUND
1-Methyl-4-phenylpyridinium (MPP+) causes a neuronal cell injury that is similar to the findings observed in Parkinson's disease. Caffeoylquinic acid derivatives have demonstrated anti-oxidant and anti-inflammatory effects. Nevertheless, the effect of 3,4,5-tricaffeoylquinic acid (3,4,5-triCQA) on the neuronal cell death due to exposure of parkinsonian toxin MPP+ remains unclear.
METHODS
Using differentiated PC12 cells, the preventive effect of 3,4,5-triCQA on the MPP+-induced cell death in relation to apoptotic process was examined.
RESULTS
MPP+ induced a decrease in Bid, Bcl-2 and survivin protein levels, increase in Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. 3,4,5-Tricaffeoylquinic acid attenuated the MPP+-induced changes in the apoptosis-related protein levels, formation of reactive oxygen species, depletion of GSH, nuclear damage and cell death. 3,4,5-Tricaffeoylquinic acid attenuated another parkinsonian neurotoxin rotenone-induced cell death.
CONCLUSIONS
3,4,5-Tricaffeoylquinic acid may attenuate the MPP+-induced apoptosis in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect seems to be ascribed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH.

Keyword

3,4,5-Tricaffeoylquinic acid; 1-Methyl-4-phenylpyridinium; PC12 cells; Apoptosis-related proteins; Protection

MeSH Terms

1-Methyl-4-phenylpyridinium
Animals
Apoptosis*
Caspases
Cell Death
Cytochromes c
Membrane Potentials
Neurons
Parkinson Disease
PC12 Cells
Reactive Oxygen Species
1-Methyl-4-phenylpyridinium
Caspases
Cytochromes c
Reactive Oxygen Species