Mitochondria are susceptible to redox impairment, which has been associated with neurodegeneration. These organelles are both a source and target of reactive species. In that context, there is increasing interest in finding natural compounds that modulate mitochondrial function and mitochondria-related signaling in order to prevent or to treat diseases involving mitochondrial impairment. Herein, we investigated whether and how pinocembrin (PB) would prevent mitochondrial dysfunction elicited by the exposure of human neuroblastoma SH-SY5Y cells to hydrogen peroxide (HO). PB (25 μM) was administrated for 4 h before HO treatment (300 μM for 24 h). PB prevented HO-induced loss of cell viability mitochondrial depolarization in SH-SY5Y cells. PB also attenuated redox impairment in mitochondrial membranes. The production of superoxide anion radical (O) and nitric oxide (NO) was alleviated by PB in cells exposed to HO. PB suppressed the HO-induced inhibition of the tricarboxylic acid (TCA) cycle enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Furthermore, PB induced anti-inflammatory effects by abolishing the HO-dependent activation of the nuclear factor-κB (NF-κB) and upregulation of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The PB-induced antioxidant and anti-inflammatory effects are dependent on the heme oxygenate-1 (HO-1) enzyme and on the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), since HO-1 inhibition (with 0.5 μM ZnPP IX) or Nrf2 silencing (with small interfering RNA (siRNA)) abolished the effects of PB. Overall, PB afforded cytoprotection by the Nrf2/HO-1 axis in HO-treated SH-SY5Y cells.
Mitochondria are the major site of ATP production in mammalian cells. Furthermore, these organelles are a source and a target of reactive oxygen species (ROS), such as radical anion superoxide (O) and hydrogen peroxide (HO). The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is the master regulator of the mammalian redox biology and controls the expression of antioxidant and phase II detoxifying enzymes in several cell types. Naringenin (NGN, 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one), a flavanone, exhibits cytoprotective effects by acting as an antioxidant and anti-inflammatory agent. NGN is a potent activator of Nrf2. Nonetheless, it was not examine yet whether NGN would induce mitochondrial protection in cells under redox stress. Therefore, we investigate here whether Nrf2 would be involved in the mitochondrial protection elicited by NGN in SH-SY5Y cells exposed to HO. We observed that a pretreatment with NGN at 80 µM for 2 h reduced the levels of lipid peroxidation, protein carbonylation, and protein nitration in the membranes of mitochondria obtained from HO-treated SH-SY5Y cells. Additionally, NGN prevented the HO-induced impairment in the function of the enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. The activites of the complexes I and V, as well as the production of ATP, were restored by NGN. NGN also suppressed the HO-induced mitochondria-related apoptosis. Interestingly, NGN promoted an increase in the levels of both total and mitochondrial glutathione (GSH). Silencing of Nrf2 abolished the protective effects induced by NGN. Overall, NGN induced mitochondrial protection by an Nrf2-dependent mechanism in HO-treated SH-SY5Y cells.
The goal of this article was to compare the effects of a prolonged use of organic and transgenic soy on the lipid profile and ovary and uterus morphology. Wistar rats were fed three different diets from weaning until sacrifice at 15 months of age. The three diets were: casein-based diet control group (CG), organic soy-based diet group (OSG), or transgenic soybased diet group (GMSG). There were no differences in food consumption or in the diet isoflavone components among the groups. Compared with the CG diet, both the OSG and GMSG diets were associated with significant reductions in body weight, serum triglycerides, and cholesterol (P < 0.05) (CG ¼ 406 AE 23.1; 104.3 AE 13.2; 119.9 AE 7.3 GMSG ¼ 368 AE 17.6; 60.3 AE 4.6; 83.3 AE 5.7 OSG ¼ 389 AE 23.5; 72.3 AE 12.5; 95.5 AE 8.0, respectively). The volume density of endometrial glandular epithelium was greater in the GMSG group (29.5 AE 7.17, P < 0.001) when compared with the CG (18.5 AE 7.4) and OSG (20.3 AE 10.6) groups. The length density of endometrial glandular epithelium was shorter in both GMSG (567.6 AE 41.1) and OSG (514.8 AE 144.5) diets compared with the CG (P < 0.05) diet. GMSG also resulted in reduced follicle number and increased corpus luteum number compared to the OSG or CG diets (P < 0.05). In summary, both GMSG and OSG diets resulted in decreased body weight and lower serum triglyceride and cholesterol levels, and alterations in uterine and ovarian morphology were also observed. The prolonged use of soybased diets and their relation to reproductive health warrants further investigation. Anat Rec, 292:587-594, 2009. V V C 2009 Wiley-Liss, Inc.
Mitochondrion is the main site of ATP production in animal cells and also orchestrates signaling pathways associated with cell survival and death. Mitochondrial dysfunction has been linked to bioenergetics and redox impairment in human diseases, such as neurodegeneration and cardiovascular disease. Protective agents able to attenuate mitochondrial impairment are of pharmacological interest. Gastrodin (GAS; 4-hydroxybenzyl alcohol 4-O-beta-D-glucoside) is a phenolic glucoside obtained from the Chinese herbal medicine Gastrodia elata Blume and exhibits antioxidant, anti-inflammatory, and antiapoptotic effects in several cell types. GAS is able to cross the blood-brain barrier, reducing the impact of different stressors on the cognition of experimental animals. In the present work, we investigated whether GAS would protect mitochondria of human SH-SY5Y neuroblastoma cells against an exposure to a pro-oxidant agent. The cells were treated with GAS at 25 μM for 30 min before the administration of hydrogen peroxide (HO) at 300 μM for an additional 3 or 24 h, depending on the assay. We evaluated both mitochondrial redox state and function parameters and analyzed the mechanism by which GAS protected mitochondria in this experimental model. Silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor suppressed the GAS-induced mitochondrial protection seen here. Moreover, Nrf2 knockdown abrogated the effects of GAS on cell viability, indicating a potential role for Nrf2 in both mitochondrial and cellular protection promoted by GAS. Further research would be necessary to investigate whether GAS would be able to induce similar effects in in vivo experimental models.
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