Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by β-amyloid peptides 25-35 in PC12 cells

Department of Nutrition and Food Hygiene, School of Public Health and Family Medicine, Capital Medical University, No. 10 Xitoutiao, YouAnMen, Beijing 100069, China.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience (Impact Factor: 2.58). 03/2010; 28(4):289-95. DOI: 10.1016/j.ijdevneu.2010.03.003
Source: PubMed


Genistein (GEN), a principal component of soybean isoflavones, might possess the neuroprotective role through its antioxidant activity. However, the detailed mechanisms are unknown yet. The purpose of this study was to investigate whether GEN could alleviate oxidative damage induced by beta-amyloid peptides 25-35 (Abeta25-35) in PC12 cells.
The PC12 cells were pre-incubated with or without GEN for 2h following incubation with Abeta25-35 for another 24h. MTT was used to assess the cell viability. Hoechst 33342 staining was applied to determine the apoptotic cells. Confocal laser scanning microscopy was implemented to examine the reactive oxygen species (ROS) levels. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Reduced and oxidized glutathione (GSH/GSSG) ratio was analyzed by using assay kits. Western blot analysis was performed to assess the proteins expression of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS).
GEN attenuated the cytotoxicity and partially prevented apoptosis induced by Abeta25-35. GEN dramatically attenuated ROS levels induced by Abeta25-35 in PC12 cells. In addition, GEN significantly reversed the reduction of MMP caused by Abeta25-35 to maintain the normal levels of the cells. The GSH/GSSG ratio in GEN pretreated groups significantly increased compared to the groups without GEN pretreatment. GEN reversed Abeta25-35 induced down regulation of the protein expression of gamma-GCS, Nrf2 and HO-1.
GEN could alleviate the oxidative stress caused by Abeta25-35 treatment and maintain redox balance in PC12 cells, which might be associated with the regulation of Nrf2/HO-1 signal pathway.

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    • "Soy isoflavones may counteract this process by upregulating serum and brain tissue antioxidant levels [56]. In addition, soy isoflavones may reduce reactive oxygen species (oxidants) and ameliorate amyloid--induced cellular apoptosis [57]. A further mechanism of action for soy isoflavones may involve reduction of amyloid fibril accumulation [58]. "
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    • "Aglycones forms exhibit higher biological activity and are more metabolically that can be absorved faster in higher amounts than glycosides (Izumi et al. 2000). The isoflavones are associated with the risk reduction or prevention of various diseases, such as breast cancer and prostate cancer (Liggins et al. 2000), osteoporosis, menopause symptoms (Levis et al. 2010), cardiovascular disease (Rimbach et al. 2008), improved memory (Lephart et al. 2002), estrogenic and antioxidant activity (Liu et al. 2010; Ma et al. 2010). Soy contains 2% of the aglycones in relation of the total isoflavones (Matsuura and Obata 1993). "
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    • "Genistein is the aglycone of genistin, which is one of the major isoflavones found in unprocessed soybeans, and it is more abundant in various soy-based products that are currently consumed around the world. Genistein has been shown to have several beneficial functions, including antioxidant [9,10], anti-inflammatory [11], immuno-modulation [12] and anti-carcinogenic effects [13,14]. Furthermore, because genistein has been demonstrated to act as a bone-sparing and antiresorptive agent, it has been considered to be a phytoestrogen [15]. "
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