J Korean Neurol Assoc.  2012 Nov;30(4):284-292.

Inhibitory Effect of Flavonoid Luteolin on 6-Hydroxydopamine Cytotoxicity via Suppression of Apoptosis-Related Protein Activation

Affiliations
  • 1Department of Neurology, Veterans Health Service Medical Center, Seoul, Korea.
  • 2Department of Pharmacology, Chung-Ang University College of Medicine, Seoul, Korea. leecs@cau.ac.kr

Abstract

BACKGROUND
Flavonoid luteolin has been shown to exhibit cell protective effect. However, it is still uncertain whether the effect of luteolin on cellular toxicity of the parkinsonian toxin 6-hydroxydopamine is mediated by apoptosis-related protein activation.
METHODS
In differentiated PC12 cells exposed to 6-hydroxydopamine in combination with luteolin, we observed the apoptosis-related protein activation, nuclear damage, formation of reactive oxygen species and cell death.
RESULTS
6-Hydroxydopamine caused apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin levels, increase in Bax levels, cytochrome c release and activation of caspases. Treatment with luteolin reduced changes in the apoptosis-related protein levels, formation of reactive oxygen species, nuclear damage and cell death.
CONCLUSIONS
Luteolin may reduce the 6-hydroxydopamine-induced apoptosis in differentiated PC12 cells by suppressing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The preventive effect of luteolin may be associated with its inhibitory effect on the production of reactive oxygen species. Luteolin may attenuate the oxidative stress and mitochondrial dysfunction-induced neuronal cell death take place in Parkinson's disease.

Keyword

6-Hydroxydopamine; Apoptosis-related proteins; Flavonoid luteolin; PC12 cells; Protective effect; Reactive oxygen species

MeSH Terms

Animals
Apoptosis
Caspases
Cell Death
Cytochromes c
Hypogonadism
Luteolin
Mitochondrial Diseases
Neurons
Ophthalmoplegia
Oxidative Stress
Oxidopamine
Parkinson Disease
PC12 Cells
Reactive Oxygen Species
Caspases
Cytochromes c
Hypogonadism
Luteolin
Mitochondrial Diseases
Ophthalmoplegia
Oxidopamine
Reactive Oxygen Species
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