AGEs Induce Apoptosis in Rat Osteoblast Cells by Activating the Caspase-3 Signaling Pathway Under a High-Glucose Environment In Vitro

2015 ◽  
Vol 178 (5) ◽  
pp. 1015-1027 ◽  
Author(s):  
Jiaqiang Liu ◽  
Jing Mao ◽  
Yi Jiang ◽  
Lunguo Xia ◽  
Lixia Mao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Caspase 3 ◽  
Osteoblast Cells ◽  
Rat Osteoblast

Emodin Ameliorate High Glucose-induced Podocyte Apoptosis via Regulating AMPK/mTOR- mediated Autophagy Signaling Pathway

2021 ◽  
Author(s):  
Hong Liu ◽  
Yanglin Hu ◽  
Ge Shi ◽  
Wenqiang Yang ◽  
Fei Xiong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Therapeutic Option ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Trypan Blue Exclusion ◽  
Compound C

Abstract Background: Podocyte apoptosis and autophagy dysfunction have been considered to be one of the important causes of diabetic nephropathy (DN). Emodin has the function of regulating autophagy. The present study was performed to investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to the induction of AMPK/mTOR-mediated autophagy in MPC5 cells in vitro.Methods: The viability and apoptosis of podocytes (MPC5 cells) were detected using CCK-8 assay, trypan blue exclusion assay and flow cytometry analysis, respectively. The expression levels of Cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were evaluated with western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.Results: HG (20-160 mmol/L) dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 μmol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage. Emodin (4 μmol/L) significantly increased LC3-II levels and induced RFP-LC3-containing punctate structures in MPC5 cells. Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 μmol/L) abolished emodin-induced autophagy activation.Conclusion: Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for DN.

scholarly journals (Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose

2015 ◽  
Vol 309 (3) ◽  
pp. E302-E310 ◽  
Author(s):  
Caixia Li ◽  
Helmy M. Siragy
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Autophagic Flux ◽  
Bafilomycin A1 ◽  
Mtor Signaling Pathway ◽  
Autophagosome Formation ◽  
Podocyte Injury ◽  
Protein Levels

High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62. In contrast, high glucose decreased activation of UNC-51-like kinase-1 (ULK1) by phosphorylating Ser757 and protein levels of microtubule-associated protein-1 light chain 3B (LC3B)-II and Lamp-2. Bafilomycin A1 increased LC3BII and p62 accumulation in high-glucose-treated cells. High glucose reduced the autophagic flux. Confocal microscopy studies showed significant reduction in the protein level of LC3B in response to high glucose. Cyto-ID autophagy staining showed a significant decrease in autophagosome formation with high glucose. In the absence of PRR, activation of Akt with sc-79 or mTOR with MHY-1485 increased p62 accumulation. Caspase-3/7 activity and apoptosis monitored by TUNEL assay were significantly increased in podocytes treated with high glucose. PRR siRNA significantly reversed the effects of high glucose. Based on these data, we conclude that high glucose decreases autophagy and increases apoptosis in mouse podocytes through the PRR/PI3K/Akt/mTOR signaling pathway.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

scholarly journals Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by high glucose through PI3K/Akt/caspase-3 signaling pathway

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Yao Ming-yan ◽  
Zhang Jing ◽  
Guo Shu-qin ◽  
Bai Xiao-liang ◽  
Li Zhi-hong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
High Glucose ◽  
Caspase 3 ◽  
Maximum Effect ◽  
Ros Generation ◽  
Protective Effects ◽  
Small Interfering Rnas ◽  
Nucleus Pulposus Cells ◽  
Pi3k Inhibitor Ly294002

Abstract Diabetes mellitus (DM) is a potential etiology of disc degeneration. Glucagon-like peptide-1 (GLP-1) is currently regarded as a powerful treatment option for type 2 diabetes. Apart from the beneficial effects on glycaemic control, GLP-1 has been reported to exert functions in a variety of tissues on modulation of cell proliferation, differentiation, and apoptosis. However, little is known regarding the effects of GLP-1 on nucleus pulposus cells (NPCs). In the present study, we investigated the effects of liraglutide (LIR), a long-lasting GLP-1 analogue, on apoptosis of human NPCs and the underlying mechanisms involved. We confirmed the presence of GLP-1 receptor (GLP-1R) in NPCs. Our data demonstrated that liraglutide inhibited the apoptosis of NPCs induced by high glucose (HG), as detected by Annexin V/Propidium Iodide (PI) and ELISA assays. Moreover, liraglutide down-regulated caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further analysis suggested that liraglutide suppressed reactive oxygen species (ROS) generation and stimulated the phosphorylation of Akt under HG condition. Pretreatment of cells with the Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY) and small interfering RNAs (siRNAs) GLP-1R abrogated the liraglutide-induced activation of Akt and the protective effects on NPCs’ apoptosis. In conclusion, liraglutide could directly protect NPCs against HG-induced apoptosis by inhibiting oxidative stress and activate the PI3K/Akt/caspase-3 signaling pathway via GLP-1R.

scholarly journals Inhibition of TGF-β Signaling in Gliomas by the Flavonoid Diosmetin Isolated from Dracocephalum peregrinum L.

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 192 ◽  
Author(s):  
Yuli Yan ◽  
Xingyu Liu ◽  
Jie Gao ◽  
Yin Wu ◽  
Yuxin Li
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Glioma Cells ◽  
Chinese Herbs ◽  
Migration And Invasion ◽  
Western Blots ◽  
E Cadherin

Background: Dracocephalum peregrinum L., a traditional Kazakh medicine, has good expectorant, anti-cough, and to some degree, anti-asthmatic effects. Diosmetin (3′,5,7-trihydroxy-4′-methoxyflavone), a natural flavonoid found in traditional Chinese herbs, is the main flavonoid in D. peregrinum L. and has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic, and anti-inflammatory effects. The present study aimed to investigate the effects of diosmetin on the proliferation, invasion, and migration of glioma cells, as well as the possible underlying mechanisms. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound, and Transwell assays were used to demonstrate the effects of diosmetin in glioma. Protein levels of Bcl-2, Bax, cleaved caspase-3, transforming growth factor-β (TGF-β), E-cadherin, and phosphorylated and unphosphorylated smad2 and smad3 were determined by Western blots. U251 glioma cell development and progression were measured in vivo in a mouse model. Results: Diosmetin inhibited U251 cell proliferation, migration, and invasion in vitro, the TGF-β signaling pathway, and Bcl-2 expression. In contrast, there was a significant increase in E-cadherin, Bax, and cleaved caspase-3 expression. Furthermore, it effectively reduced the tumorigenicity of glioma cells and promoted apoptosis in vivo. Conclusion: The results of this study suggest that diosmetin suppresses the growth of glioma cells in vitro and in vivo, possibly by activating E-cadherin expression and inhibiting the TGF-β signaling pathway.

scholarly journals Hyperoside Induces Breast Cancer Cells Apoptosis via ROS-Mediated NF-κB Signaling Pathway

2019 ◽  
Vol 21 (1) ◽  
pp. 131 ◽  
Author(s):  
Jinxia Qiu ◽  
Tao Zhang ◽  
Xinying Zhu ◽  
Chao Yang ◽  
Yaxing Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
B Cell Lymphoma ◽  
Flavonoid Glycosides

Hyperoside (quercetin 3-o-β-d-galactopyranoside) is one of the flavonoid glycosides with anti-inflammatory, antidepressant, and anti-cancer effects. But it remains unknown whether it had effects on breast cancer. Here, different concentrations of hyperoside were used to explore its therapeutic potential in both breast cancer cells and subcutaneous homotransplant mouse model. CCK-8 and wound healing assays showed that the viability and migration capability of Michigan Cancer Foundation-7 (MCF-7) and 4T1 cells were inhibited by hyperoside, while the apoptosis of cells were increased. Real-time quantitative PCR (qRT-PCR) and western blot analysis were used to detect mRNA and the protein level, respectively, which showed decreased levels of B cell lymphoma-2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP), and increased levels of Bax and cleaved caspase-3. After exploration of the potential mechanism, we found that reactive oxygen species (ROS) production was reduced by the administration of hyperoside, which subsequently inhibited the activation of NF-κB signaling pathway. Tumor volume was significantly decreased in subcutaneous homotransplant mouse model in hyperoside-treated group, which was consistent with our study in vitro. These results indicated that hyperoside acted as an anticancer drug through ROS-related apoptosis and its mechanism included activation of the Bax–caspase-3 axis and the inhibition of the NF-κB signaling pathway.

scholarly journals Relaxin Attenuates Contrast-Induced Human Proximal Tubular Epithelial Cell Apoptosis by Activation of the PI3K/Akt Signaling Pathway In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Xiang-Cheng Xie ◽  
Yizhi Cao ◽  
Xiu Yang ◽  
Qun-Hong Xu ◽  
Wei Wei ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Bax Protein ◽  
Phosphorylated Akt

Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms.Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method. Apoptosis was detected with Annexin V staining. Western blot analysis was employed to measure the expression of pAkt (S473), Akt, cleaved caspase-3, Bcl-2, Bax, and actin proteins.Results. Ioversol reduced the viability of HK-2 cells. Western blotting results revealed decreased expression of phosphorylated Akt in cells treated with ioversol. The activities of caspase-3 and Bax protein increased, while the expression of Bcl-2 protein decreased. As a result, the Bax/Bcl-2 ratio increased after treatment with ioversol. These effects were reversed when HK-2 cells were cotreated with RLX. However, with preadministration of PI3K/Akt pathway inhibitor LY294002, the effect of RLX was blocked.Conclusion. Our study demonstrates that relaxin attenuates ioversol induced cell apoptosis via activation of the PI3K/Akt signaling pathway, suggesting that RLX might play a protective role in the treatment of CI-AKI.

TNF-α is upregulated in T2DM patients with fracture and promotes the apoptosis of osteoblast cells in vitro in the presence of high glucose

Cytokine ◽  
2016 ◽  
Vol 80 ◽  
pp. 35-42 ◽  
Author(s):  
Mingqi Sun ◽  
Junli Yang ◽  
Jianzhong Wang ◽  
Ting Hao ◽  
Dianming Jiang ◽  
...  
Keyword(s):  
High Glucose ◽  
Osteoblast Cells ◽  
Tnf Α

scholarly journals Hydrogen Sulfide Ameliorates High Glucose-induced Inflammation Through SIRT1-mTOR/NF-κB Signaling Pathway in HT-22 cells

2020 ◽  
Author(s):  
Xinrui Li ◽  
Yinghua Yu ◽  
Peiquan Yu ◽  
Ting Xu ◽  
Jiao Liu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
High Glucose ◽  
Near Infrared ◽  
Neuronal Cell ◽  
Inflammatory Factors ◽  
Sodium Hydrosulfide ◽  
Protein Levels

Abstract Background: Hyperglycemia-induced neuroinflammation promotes the progression of diabetic encephalopathy (DE). Hydrogen sulfide (H2S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, its role in hyperglycemia-induced neuronal inflammation has not been investigated. Herein, we examined the effects and its related signaling pathway of H2S on inflammatory response in high glucose-treated HT-22 cells.Methods: A hippocampal neuronal cell line, HT-22, was used as an in vitro model to explore the function of H2S on inflammatory response triggered by high glucose. A dicyanoisophorone-based near-infrared fluorescent probe (NIR-NP) was synthesized to detect H2S levels in HT-22 cells. Western blotting, immunofluorescence and real time-qPCR were carried out to study the mechanism of action for H2S.Results: We found that high glucose (85 mM) decreased the level of endogenous H2S and the expression of cystathionine-β-synthase (CBS) which is the main enzyme for H2S production in the brain. Sodium hydrosulfide (NaHS, a H2S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) administration restored high glucose-induced downregulation of CBS and H2S levels. Importantly, high glucose upregulated the level of pro-inflammatory factors (IL-1β, IL-6, TNF-α) in HT-22 cells. Treatment with NaHS or SAMe alleviated this enhanced transcription of these pro-inflammatory factors, suggesting that H2S might ameliorate high glucose-induced inflammation in HT-22 cells. We also found that high glucose reduced SIRT1 protein levels. SIRT1 reduction elevated the level of p-mTOR, p-NF-κB and pro-inflammatory factors, which were restored by resveratrol (a SIRT1 agonist). These results suggested that SIRT1 might be an upstream mediator of mTOR/NF-κB signaling pathway. Furthermore, NaHS or SAMe treatment reversed the expression of SIRT1, mTOR and NF-κB under high glucose conditions.Conclusions: Our study revealed that high glucose decreased CBS to reduce the production of H2S, which in turn decreased the expression of SIRT1. The reduction of SIRT1 activated mTOR/NF-κB signaling to promote inflammation. Given that promoting H2S production using NaHS or SAMe can reverse high glucose-induced inflammatory response, our study might shed light on the prophylactic treatment of DE.

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