1.
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.
2.
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.
3.
Role of the Wilms' tumor 1 gene in the aberrant biological behavior of leukemic cells and the related mechanisms.
Li, Y, Wang, J, Li, X, Jia, Y, Huai, L, He, K, Yu, P, Wang, M, Xing, H, Rao, Q, et al
Oncology reports. 2014;(6):2680-6
Abstract
The Wilms' tumor 1 (WT1) gene is one of the regulating factors in cell proliferation and development. It is a double-functional gene: an oncogene and a tumor suppressor. This gene was found to be highly expressed in many leukemic cell lines and in patients with acute myeloid leukemia. In the present study, we demonstrated that the WT1 gene was commonly expressed in leukemic cell lines apart from U937 cells. The K562 cell line which expresses WT1 at a high level (mRNA and protein) was used in the entire experiment. By MTT and colony formation assays, we found that curcumin, an inhibitor of the WT1 protein, inhibited cell proliferation and clonogenicity in a time- and dose-dependent manner. It also caused cell cycle arrest at the G2/M phase. We then designed specific short hairpin RNAs (shRNAs) which could downregulate WT1 by 70-80% at the mRNA and protein levels. Reduction in the WT1 levels attenuated the proliferative ability and clonogenicity. Cell cycle progression analysis indicated that the proportion of cells in the G0/G1 phase increased while the proportion in the S phase decreased distinctively. ChIP-DNA selection and ligation (DSL) experiment identified a cohort of genes whose promoters are targeted by WT1. These genes were classified into different cellular signaling pathways using MAS software and included the Wnt/β-catenin pathway, MAPK signaling pathway, apoptosis pathway, and the cell cycle. We focused on the Wnt/β-catenin signaling pathway, and compared expression of several genes in the K562 cells transfected with the control shRNA and WT1-specific shRNA. β-catenin, an important gene in the Wnt canonical pathway, was downregulated after WT1 RNAi. Target genes of β-catenin which participate in cell proliferation and cell cycle regulation, such as CCND1 and MYC, were also significantly downregulated. Collectively, these data suggest that WT1 functions as an oncogene in leukemia cells, and one important mechanism is regulation of the Wnt/β-catenin pathway.