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Attenuation of Oxidative Stress-Induced Osteoblast Apoptosis by Curcumin is Associated with Preservation of Mitochondrial Functions and Increased Akt-GSK3β Signaling.
Dai, P, Mao, Y, Sun, X, Li, X, Muhammad, I, Gu, W, Zhang, D, Zhou, Y, Ni, Z, Ma, J, et al
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;(2):661-677
Abstract
BACKGROUND Osteoblast apoptosis induced by oxidative stress plays a crucial role in the development and progression of osteoporosis. Curcumin, a natural antioxidant isolated from Curcuma longa, has highly protective effects against osteoporosis. However, the effects of curcumin on oxidative stress-induced osteoblast apoptosis remain unclear. This study aimed to explore the effect of curcumin on hydrogen peroxide (H2O2) induced osteoblast apoptosis and the underlying mechanisms. METHODS An osteoblastic cell line (Saos-2) was exposed to various concentrations of H2O2 with or without curcumin treatment. Cell viability was evaluated by MTT assays. The apoptosis rate was analyzed by flow cytometry and TUNEL assays. Mitochondrial ROS and membrane potential were determined using a fluorescence microscope. Mitochondrial respiratory enzyme activity was measured using a spectrophotometer. Protein levels were detected by western blotting. RESULTS Curcumin was cytoprotective because it greatly improved the viability of Saos-2 cells exposed to H2O2 and attenuated H2O2-induced apoptosis. Curcumin treatment also preserved the mitochondrial redox potential, decreased the mitochondrial oxidative status, and improved the mitochondrial membrane potential and functions. Furthermore, curcumin treatment markedly increased levels of phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3β (GSK3β). CONCLUSION Curcumin administration ameliorates oxidative stress-induced apoptosis in osteoblasts by preserving mitochondrial functions and activation of Akt-GSK3β signaling. These data provide experimental evidence supporting the clinical use of curcumin for prevention or treatment of osteoporosis.
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Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway.
Wang, J, Liu, H, Zhang, X, Li, X, Geng, L, Zhang, H, Zhang, Q
Marine drugs. 2017;(4)
Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H₂O₂-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.
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Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies.
Yang, H, Xu, W, Zhou, Z, Liu, J, Li, X, Chen, L, Weng, J, Yu, Z
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2015;(6):360-7
Abstract
Curcumin has a therapeutic potential in treating diabetic kidney disease (DKD) while potential mechanisms underlining this beneficial effect remain to be elucidated. In the present study, curcumin intervention was performed in patients with Type II diabetes mellitus (T2DM) by oral intake of curcumin at the dose of 500 mg/day for a period of 15-30 days. Nephritic excretion of urinary micro-albumin (U-mAlb) and blood metabolic indexes were assessed before and after this intervention. In addition, the lipid oxidation index, malondialdehyde (MDA) in plasma and the status of anti-oxidative Nrf2 system in blood lymphocytes were measured. The effect of curcumin on inflammation was assessed by measuring plasma lipopolysaccharide (LPS) content and inflammatory signaling protein in blood lymphocytes. A self-comparison method was used for assessing statistical significances of these measurements. Here we show that curcumin intervention markedly attenuated U-mAlb excretion without affecting metabolic control of participated patients. In addition, curcumin reduced plasma MDA level with enhanced the Nrf2 system specifically regulated protein, NAD(P)H quinone oxidoreductase 1 (NQO-1) together with other anti-oxidative enzymes in patients' blood lymphocytes. Furthermore, we observed reduced plasma LPS content and increased IκB, an inhibitory protein on inflammatory signaling in patient's lymphocytes after curcumin administration. Finally, several gut bacterials important for maintaining gut barrier integrity and function were upregulated by curcumin.In conclusion, short-term curcumin intervention ablates DKD progress with activating Nrf2 anti-oxidative system and anti-inflammatory efficacies in patients with T2DM.
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[Ovarian carcinoma cell inhibits T cell JAK-STAT signal transduction pathway, an experimental study].
Wang, H, Xie, X, Lü, WG, Ye, DF, Chen, HZ, Li, X, Cheng, Q
Zhonghua yi xue za zhi. 2003;(11):972-5
Abstract
OBJECTIVE To investigate the effect of ovarian carcinoma cell on T cell JAK-STAT signal transduction pathway and its role in the ovarian carcinoma induced immunosupression. METHODS Human ovarian carcinoma cells of OVCAR3. CAOV3, and SKOV3 lines were cultured. CD8(+) T cells were isolated from the peripheral venous blood of healthy persons. Then the supernatants of these ovarian carcinoma cell lines and RPMI-1640 were added into the culture of CD8(+) T cells (groups I, II, III, and control). Thiazolyl blue (MTT) method was used to detect the growth of CD8(+) T cell. The cell cycle was examined by flow cytometry. The secretion of the Tc1 type cytokine interferon (IFN)-gamma mRNA and the secretion of the Tc2 type cytokine interleukin (IL)-10 mRNA were detected by RT-PCR. The expression of signaling molecules JAK and JAK3 and the phosphorylated activation of STAT3 and STAT5 in the CD8(+) T cell were analyzed by Western blotting. RESULTS The absorbance at the wavelength 570 nm of CD8(+) T cell culture was 0.23 +/- 0.03, 0.28 +/- 0.06, and 0.29 +/- 0.05 in the group I, II, and III, all significantly lower than that in the group IV (0.79 +/- 0.07, all P < 0.01). The percentages of CD8(+) T cells at the stage S and stage G(2)/M were lower, and those in stage G(1)/G(0) were higher in groups I, II, and III than in group IV (all P < 0.01). The IFN-gamma expression was significantly lower in groups I, II, and III in comparison with that in group IV. However, the expression of IL-10 was significantly higher in groups I, II, and III in comparison with that in group IV. The expression of JAK3 protein, but not JAK1 protein, was significantly lower in groups I, II, and III in comparison with that in group IV. The phosphorylated activation of STAT5 was suppressed significantly in groups I, II, and III, whereas the phosphorylated activation of STAT3 was suppressed only in group I. CONCLUSION Ovarian carcinoma may suppress T cell proliferation through inhibition of the JAK-STAT signal transduction pathway, which may be a mechanism of ovarian carcinoma induced immunosuppression.