Epigallocatechin-3-gallate suppresses 1-methyl-4-phenyl-pyridine-induced oxidative stress in PC12 cells via the SIRT1/PGC-1α signaling pathway

Department of Neurology, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.
BMC Complementary and Alternative Medicine (Impact Factor: 2.02). 06/2012; 12(1):82. DOI: 10.1186/1472-6882-12-82
Source: PubMed


Parkinson's disease is a high incidence neurodegenerative disease in elderly people, and oxidative stress plays an important role in the pathogenesis. Oxygen metabolism in the brain is high, which lacks an antioxidative protection mechanism. Recently, it has been found that polyphenols play an important role in antioxidation. (-)-epigallocatechin-3-gallate (EGCG) is an important component of tea polyphenols and its biological effects, such as strong antioxidation, scavenging of free radicals and anti-apoptosis, can pass through the blood brain barrier. The SIRT1/PGC-1α signaling pathway has not been reported in PC12 cells. Therefore, research of the protective mechanism of EGCG in PC12 cells damaged by -methyl-4-phenyl-pyridine (MMP+) may provide a new insight into protect against and treatment of Parkinson's disease.
MPP(+)-treated highly differentiated PC12 cells were used as the in vitro cell model. An MTT assay was used to investigate cell viability after EGCG treatment, a dichlorofluorescin diacetate assay was used to measure reactive oxygen species (ROS) production, western blot analysis was used to observe PGC-1α and SIRT1 protein expression, and real-time PCR to observe PGC-1α, SOD1 and GPX1 mRNA expression.
PC12 cell viability was significantly reduced after MPP(+) treatment by 11.46% compared with that of the control (P < 0.05). However, cell viability was unchanged by 10 μmol/L EGCG treatment. In co-treatments with EGCG and MPP(+), cell viability was significantly increased by 12.92% (P < 0.05) and MPP(+)-induced ROS production was markedly decreased. PGC-1α mRNA expression was obviously upregulated by 21.51% (P < 0.05), and SOD1 and GPX1 mRNA expression was slightly increased by 12.94% and 15.63% (P > 0.05), respectively, by treatment with EGCG and then MPP(+) for 12 h. The mRNA expression of PGC-1α, SOD1 and GPX1 was increased by 25.17%, 40% and 146% (all P < 0.05), respectively, by treatment with EGCG and then MPP(+) for 24 h. Such effects were not observed with MPP(+) treatment alone.
The SIRT1/PGC-1α pathway is one of the mechanisms of EGCG suppression of MPP(+)-induced injury of PC12 cells.

Download full-text


Available from: Yuangui Zhu, May 20, 2014
  • Source
    • "1.25–10 M Rat pheochromocytoma PC12 cells MPP + ↑SIRT1/PGC-1 ** [70] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigallocatechin gallate (EGCG) is a flavonoid belonging to the chemical class of falvan-3-ols (catechins) esterified with gallic acid. It is the main catechin found in green tea (Camellia sinensis L.) accounting for about 50% of its total polyphenols. Extensive research performed in recent years has revealed that green tea demonstrates a wide range of positive biological activities against serious chronic diseases such as cardiovascular and neurodegenerative pathologies, cancer, metabolic syndrome and type 2 diabetes. These protective properties can be traced back to the potent antioxidant and anti-inflammatory activities of EGCG. Recent studies have suggested that it may exert its beneficial effects by modulating mitochondrial functions impacting mitochondrial biogenesis, bioenergetic control (ATP production and anabolism), alteration of the cell cycle, and mitochondria-related apoptosis. This review evaluates recent evidence on the ability of EGCG to exert critical influence on the above mentioned pathways.
    Full-text · Article · Dec 2015 · Pharmacological Research
  • Source
    • "In addition to resveratrol, other phytochemicals that have been reported to increase SIRT1 activity in neuronal cells or animal models include epigallocatechin-3-gallate (Ye et al., 2012), quercetin (Davis et al., 2009), icariin (Wang et al., 2009; Zhang et al., 2010; Zhu et al., 2010), baicalin (Chen et al., 2011), caffeic acid and rosmarinic acid (Pietsch et al., 2011), persimmon oligomeric proanthocyanidins (Yokozawa et al., 2009), butein, fisetin and piceatannol (Howitz et al., 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The impact of dietary factors on brain health and vulnerability to disease is increasingly appreciated. The results of epidemiological studies, and intervention trials in animal models suggest that diets rich in phytochemicals can enhance neuroplasticity and resistance to neurodegeneration. Here we describe how interactions of plants and animals during their co-evolution, and resulting reciprocal adaptations, have shaped the remarkable characteristics of phytochemicals and their effects on the physiology of animal cells in general, and neurons in particular. Survival advantages were conferred upon plants capable of producing noxious bitter-tasting chemicals, and on animals able to tolerate the phytochemicals and consume the plants as an energy source. The remarkably diverse array of phytochemicals present in modern fruits, vegetables spices, tea and coffee may have arisen, in part, from the acquisition of adaptive cellular stress responses and detoxification enzymes in animals that enabled them to consume plants containing potentially toxic chemicals. Interestingly, some of the same adaptive stress response mechanisms that protect neurons against noxious phytochemicals are also activated by dietary energy restriction and vigorous physical exertion, two environmental challenges that shaped brain evolution. In this perspective article, we describe some of the signaling pathways relevant to cellular energy metabolism that are modulated by 'neurohormetic phytochemicals' (potentially toxic chemicals produced by plants that have beneficial effects on animals when consumed in moderate amounts). We highlight the cellular bioenergetics-related sirtuin, adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 (IGF-1) pathways. The inclusion of dietary neurohormetic phytochemicals in an overall program for brain health that also includes exercise and energy restriction may find applications in the prevention and treatment of a range of neurological disorders. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · Neurochemistry International
  • Source
    • "Given that microglia play a key role in the generation of free radicals and inflammatory factors in the brain, EGCG was classified as neuroprotective in vivo (Li et al., 2004). Additionally, EGCG improved cell viability and attenuated MPP-induced intracellular ROS formation via the SIRT1/PGC-1α signaling pathway in MPP induced PC12 cells (Ye et al., 2012). EGCG reduced neuronal cell death and induced nitric oxide synthase (NOS) expression in an MPTP mouse model of PD, thus providing further evidence for its neuroprotection via NO reduction (Kim et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. It is now clear that genetic susceptibility and environmental factors play a role in disease etiology and progression. Because environmental factors are involved with the majority of the cases of PD, it is important to understand the role nutrition plays in both neuroprotection and neurodegeneration. Recent epidemiological studies have revealed the promise of some nutrients in reducing the risk of PD. In contrast, other nutrients may be involved with the etiology of neurodegeneration or exacerbate disease progression. This review summarizes the studies that have addressed these issues and describes in detail the nutrients and their putative mechanisms of action in PD.
    Full-text · Article · Mar 2014 · Frontiers in Aging Neuroscience
Show more