scholarly journals Ginkgo biloba Leaf Extract Protects against Myocardial Injury via Attenuation of Endoplasmic Reticulum Stress in Streptozotocin-Induced Diabetic ApoE−/− Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Jinfan Tian ◽  
Yanfei Liu ◽  
Yue Liu ◽  
Keji Chen ◽  
Shuzheng Lyu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Interstitial Fibrosis ◽  
Serum Levels ◽  
Cardiomyocyte Apoptosis ◽  
Mrna Levels ◽  
Caspase 12 ◽  
Apoptosis Pathways

Diabetes was induced in high-fat diet-fed ApoE−/− mice via administration of low-dose streptozotocin (STZ) for five days. Mice were then treated with GBE (200 or 400 mg/kg) by gastric gavage daily for 12 weeks. Mice in the untreated diabetic group received saline instead, and nondiabetic C57BL/6J mice served as controls. Collagen І and ІІІ mRNA expression was measured by real-time PCR. TNF-α, IL-1β mRNA levels, and NF-κB expression were determined to analyze intramyocardial inflammation. Hallmarks of endoplasmic reticulum stress- (ERS-) related apoptosis pathways, including phosphorylated c-Jun N-terminal kinase (p-JNK), C/EBP homologous protein (CHOP), caspase-12, and cleaved caspase-3, were analyzed by Western blotting. Diabetic ApoE−/− myocardial injury was associated with increased cardiomyocyte apoptosis (increased expression of p-JNK, CHOP, caspase-12, and cleaved caspase-3), interstitial fibrosis (increased mRNA levels of collagen І and ІІІ), and inflammation (increased mRNA levels of TNF-α and IL-1β, and NF-κB expression). GBE at 200 and 400 mg/kg/day significantly attenuated cardiomyocyte apoptosis, collagen deposition, and inflammation in diabetic mice via inhibition of the p-JNK, CHOP, and caspase-12 pathways. Serum levels of the proinflammatory cytokines (IL-6, IL-1β, and TNF-α), blood glucose, and lipid profiles were also regulated by GBE treatment. GBE might be beneficial in the treatment of diabetic myocardial injury.

scholarly journals Dahuang Danshen Decoction Inhibits Pancreatic Fibrosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiaoqiang Liang ◽  
Mian Han ◽  
Xuelin Zhang ◽  
Xun Sun ◽  
Kui Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Molecular Docking ◽  
Endoplasmic Reticulum Stress ◽  
Serum Levels ◽  
Pancreatic Fibrosis ◽  
Mrna Levels ◽  
Antioxidant Genes ◽  
Caspase 12

Background. In Traditional Chinese Medicine (TCM), Dahuang Danshen decoction (DD) is used to treat pancreatic fibrosis. Pancreatic fibrosis is a typical manifestation of chronic pancreatitis (CP), which affects the digestive system. The therapeutic mechanisms of DD in pancreatic fibrosis are unclear. Aim. This study aimed to investigate the regulatory mechanisms of DD on oxidative stress and endoplasmic reticulum stress in CP. Materials and Methods. Experimental rats were intraperitoneally injected with 500 mg/kg BW of diethyldithiocarbamate (DDC) twice a week for six weeks to induce CP. At the same time, DD was administered orally at daily doses of 1.37 g/kg BW, 2.74 g/kg BW, and 5.48 g/kg BW to evaluate its treatment effects on CP. After all treatments, pancreatic tissues were harvested and subjected to H&E staining. Transmission electron microscopy (TEM) was also performed to show the endoplasmic reticulum structure in the pancreatic tissues. Immunohistochemistry was used to detect the α-SMA expression level in the pancreatic tissues. Metabolomics analysis of the serum and proteomics analysis of the pancreatic tissues were performed to reveal the changes of endogenous metabolites and proteins, respectively. Concentrations of GSH, MDA, SOD, ROS, col-1, and col-3 were determined using corresponding kits. The western blotting method was used to determine the protein levels of Keap-1, HO-1, NQO1, Nrf2, GRP, JNK, and caspase 12. The pancreatic mRNA levels of NQO1, GPX1, HO-1, GST-π, GRP, JNK, and caspase 12 were also determined by quantitative PCR. The interactions between TCM components and Keap-1 were investigated by molecular docking modeling. Results. The pathohistological results demonstrated that DD could ameliorate DDC-induced CP in vivo, indicated by reduction of α-SMA, col-1, col-3, TNF-α, and IL-6. DD increased serum levels of GSH and SOD but reduced pancreatic ROS. DD decreased cytoplasmic Keap-1 and increased Nrf2 nuclear localization. Correspondingly, DD increased the expression levels of Nrf2 downstream antioxidant genes NQO1, GPX1, HO-1, and GST-π. DD also decreased ERS hallmarks caspase 12 cleavage and GRP expression. Eventually, DD inhibited PSC activation by reducing JNK phosphorylation and MMK-3/p38 expression. Molecular docking analysis showed that salvianolic acid B and emodin had a good binding affinity toward Keap-1. Conclusions. These results demonstrated that DD could ameliorate the oxidative and endoplasmic reticulum stress through releasing Nrf2 from Keap-1 binding and inducing the downstream antioxidant enzymes. As a result, DD could thwart pancreatic fibrosis by inhibiting PSCs activation, which was induced by OS and ERS through JNK and MMK3/p38 pathways.

scholarly journals Effect of Berberine from Coptis chinensis on Apoptosis of Intestinal Epithelial Cells in a Mouse Model of Ulcerative Colitis: Role of Endoplasmic Reticulum Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Shen Yan ◽  
Liu Yingchao ◽  
Wang Zhangliu ◽  
Ruan Xianli ◽  
Li Si ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Endoplasmic Reticulum Stress ◽  
Caspase 3 ◽  
Intestinal Epithelial Cells ◽  
High Dose ◽  
Intestinal Epithelial ◽  
Model Group ◽  
Caspase 12

The purpose of this study was to verify the effect of berberine (BBR) on endoplasmic reticulum stress (ERS) and apoptosis of intestinal epithelial cells (IECs) in mice with ulcerative colitis (UC). BALB/c mice were randomly divided into five groups as follows: blank control, model, and low-, medium-, and high-dose BBR. A dextran sodium sulfate- (DSS-) induced model of UC was prepared, and the low-, medium-, and high-dose BBR groups were simultaneously gavaged with a BBR suspension for 7 d. Disease activity index (DAI) was assessed, and tissue damage index (TDI) was assessed from colon samples after the last administration. TUNEL assays were used to detect apoptosis of IECs. Immunohistochemistry and/or real-time PCR were applied to determine the expression of GRP78, caspase-12, and caspase-3. In all BBR treatment groups, clinical symptoms of colitis and histopathological damage were significantly reduced. The high-dose BBR group exhibited particularly pronounced decrease (p<0.01) in both DAI (0.48 ± 0.36) and TDI (1.62 ± 0.64) relative to the model group (1.50 ± 0.65 and 3.88 ± 0.04, respectively). In colon tissues of the model group, the number of apoptotic IECs was significantly increased; the expression of GRP78, caspase-12, and caspase-3 proteins was significantly increased; and the expression of the GRP78 mRNA was upregulated. In low-, medium-, and high-dose BBR groups, the number of apoptotic IECs was significantly reduced. Moreover, GRP78 and caspase-3 expression levels were significantly decreased in the medium- and high-dose BBR groups, caspase-12 expression was significantly decreased in the high-dose BBR group, and the GRP78 mRNA expression level was significantly decreased in the high-dose BBR group. BBR can effectively reduce the rate of IEC apoptosis in UC mice and alleviate the inflammatory response in the colon. The underlying mechanism seems to involve ERS modulation and inhibition of ERS-mediated activation of the caspase-12/caspase-3 apoptosis signaling pathway.

scholarly journals Melatonin Relieves Busulfan-Induced Spermatogonial Stem Cell Apoptosis of Mouse Testis by Inhibiting Endoplasmic Reticulum Stress

2017 ◽  
Vol 44 (6) ◽  
pp. 2407-2421 ◽  
Author(s):  
Yanhua Cui ◽  
Lipeng Ren ◽  
Bo Li ◽  
Jia Fang ◽  
Yuanxin Zhai ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Caspase 3 ◽  
Survival Rates ◽  
Underlying Mechanism ◽  
Pcr Analysis ◽  
Caspase 12 ◽  
Apoptosis Proteins

Background/Aims: Busulfan is commonly used for cancer chemotherapy. Although it has the advantage of increasing the survival rate of patients, it can cause male infertility via damaging the testes and reducing sperm counts. Therefore, the underlying mechanism should be explored, and new agents should be developed to protect the male reproductive system from busulfan-induced damage. Endoplasmic reticulum stress (ERS) is considered a key contributor to numerous pathologies. Despite several studies linking ERS to toxicants, studies have yet to determine whether ERS is a contributing factor to busulfan-induced testicular damage. Melatonin is a well-known broad-spectrum antioxidant, anti-inflammatory and antitumour agent, but the effects of melatonin on busulfan-induced ERS in mouse testes damage are less documented. Methods: The effects of melatonin were measured by immunofluorescence staining, Western blot, qRT-PCR analysis and flow cytometry assay. The underlying mechanism was investigated by measuring ERS. Results: We found that ERS was strongly activated in mouse testes (in vivo) and the C18-4 cell line (in vitro) after busulfan administration. ERS-related apoptosis proteins such as caspase-12, CHOP and caspase-3 were activated, and the expression of apoptotic proteins such as P53 and PUMA were upregulated. Furthermore, we investigated whether melatonin reduced the extent of damage to mouse testes and improved the survival rates of busulfan-treated mice. When exploring the underlying mechanisms, we found melatonin could counteract ERS by decreasing the expression levels of the ERS markers GRP78, ATF6, pIRE1 and XBP1 in mouse testes and mouse SSCs (C18-4 cells). Moreover, it blocked the activation of ERS-related apoptosis proteins caspase-12, CHOP and caspase-3 and suppressed P53 and PUMA expression stimulated by busulfan both in vivo and in vitro. Conclusion: Our results demonstrate that ERS is an important mediator for busulfan-induced apoptosis. The attenuation of ERS by melatonin can prevent busulfan-treated SSCs apoptosis and protect busulfan-treated testes from damage. Thus, this study suggests that melatonin may alleviate the side effects of busulfan for male patients during clinical treatment.

scholarly journals High Doses of Dexamethasone Induce Endoplasmic Reticulum Stress-Mediated Apoptosis by Promoting Calcium Ion Influx-Dependent CHOP Expression in Osteoblasts

2021 ◽  
Author(s):  
Yunshan Guo ◽  
Dingjun Hao
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Calcium Ion ◽  
Caspase 3 ◽  
Combined Treatment ◽  
Caspase 12 ◽  
Ion Influx ◽  
High Doses ◽  
In Cells

Abstract Background: The molecular mechanisms by which dexamethasone (Dex) induces apoptosis in osteoblasts remain unclear.Materials and Methods: MC3T3-E1 cells were treated with 0, 10-8, 10-6, and 10-4 M Dex for 24 h. The expression of ATF6, and phosphorylated PERK and IRE1, cell apoptosis, and the activity of caspase-12 and caspase-3 were measured. The expression of CHOP and the rate of influx of calcium ions were also measured in cells treated with 0 and 10-4 M Dex for 24 h. The effect of 2-APB treatment was assessed in cells treated with 0 or 10-4 M Dex.Results: The levels of ATF6 and phosphorylated PERK and IRE1 increased in a dose-dependent manner in MC3T3-E1 cells treated with 10-8, 10-6, and 10-4 M Dex, compared to in cells treated with 0 M Dex (P <0.05). Cells treated with 10-6 and 10-4 M Dex had significantly increased cell apoptosis rates and caspase-12 and caspase-3 activity compared to the control (P <0.05). Cells treated with 10-4 M Dex had significantly increased levels of CHOP and calcium ion influx rates compared to in the control (P <0.05). Combined treatment with 10-4 M Dex and 2-APB abrogated the observed increases in cell apoptosis and the activity of caspase-12 and caspase-3 (P>0.05). Conclusion: High doses of Dex induce endoplasmic reticulum stress-mediated apoptosis by promoting calcium ion influx-dependent expression of CHOP, and the activation of caspase-12 and caspase-3 in osteoblasts. Combined treatment with 2-APB protects the cells from the effects of Dex, preventing endoplasmic reticulum stress-mediated apoptosis.

scholarly journals The Sodium-Glucose Co-Transporter 2 Inhibitor, Empagliflozin, Protects against Diabetic Cardiomyopathy by Inhibition of the Endoplasmic Reticulum Stress Pathway

2017 ◽  
Vol 41 (6) ◽  
pp. 2503-2512 ◽  
Author(s):  
Yang Zhou ◽  
Wei Wu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular ◽  
High Dose ◽  
Mrna Levels ◽  
Caspase 12 ◽  
Endoplasmic Reticulum Stress Pathway ◽  
Systolic And Diastolic Function ◽  
Stress Pathway

Background/Aims: This study aimed to determine whether or not the sodium-glucose co-transporter 2 inhibitor, empagliflozin (EMPA), can protect against diabetic cardiomyopathy (DCM) and to elucidate the related mechanism. Methods: Rats were divided into the following four groups: a non-diabetic group; diabetic cardiomyopathy rats without EMPA treatment; and diabetic cardiomyopathy rats with EMPA treatment (low- and high-dose EMPA). Hemodynamic measurements were performed to evaluate left ventricular systolic and diastolic function. The histopathology of the heart was examined with hematoxylin-eosin staining. Expression of glucose-regulated protein (GRP)78, enhancer-binding protein homologous protein (CHOP), and caspase-12 was detected by Western blot, and the mRNA levels of XBP1, ATF4, and TRAF2 were analysed by real-time PCR. Results: EMPA significantly decreased the blood glucose level when compared with vehicle. EMPA strongly improved cardiac function based on hemodynamic and histopathologic analyses. Moreover, EMPA can significantly down-regulate the expression of GRP78, CHOP, and caspase-12 (P < 0.01). Additionally, the mRNA levels of XBP1, ATF4, and TRAF2 were markedly decreased by administration of EMPA (P < 0.01). Conclusion: EMPA protects against DCM by inactivating the endoplasmic reticulum stress pathway.

scholarly journals Tension induces intervertebral disc degeneration via endoplasmic reticulum stress-mediated autophagy

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Jiangwei Chen ◽  
Zunwen Lin ◽  
Kui Deng ◽  
Bin Shao ◽  
Dong Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Cyclic Deformation ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Caspase 3 ◽  
Beclin 1 ◽  
Caspase 12

Abstract Background: Intervertebral disc degeneration is a common degenerative disease. The present study aimed to explore the role and mechanism of tension-induced endoplasmic reticulum stress in intervertebral disc degeneration. Methods: Intervertebral disc degeneration models of SD rat were analyzed for apoptosis, the expression of Poly(ADP-ribose) polymerase (PARP), Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP using immunohistochemistry, qPCR and Western blot analysis. Annulus fibrosus cells of intervertebral disc were isolated, subjected to cyclic deformation stress and analyzed for ROS and apoptosis, lysosome activity and expression of genes. The cells were knockdown with siRNA or treated with endoplasmic reticulum stress inhibitor 4-PBA and assayed for ROS, apoptosis, lysosome activity and gene expression. Results: Compared with the controls, intervertebral disc degeneration was observed through X-rays examinations and HS staining. Apoptosis and expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP were significantly increased in the intervertebral disc tissue of the models. In mechanic mimic experiments, the primary annulus fibrosus cells were subjected to 18% cyclic deformation, ROS and apoptosis as well as the activity of lysosome were increased. Similarly, the expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP was also increased significantly after deformation treatment. On other hand, when the cells were treated with 9 mM 4-PBA and/or CHOP-siRNA4, the apoptosis rate, ROS level, lysosome activity and expression of PARP, Caspase-12, Caspase-3, LC3, Beclin-1 and CHOP were significantly reduced. Conclusions: Autophagy reaction mediated by endoplasmic reticulum stress plays important rale in tension-induced intervertebral disc degeneration. Intervertebral disc degeneration likely results from interactions between autophagy, apoptosis and reticulum stress, and is ROS-dependent.

scholarly journals Apoptosis induced by endoplasmic reticulum stress depends on activation of caspase-3 via caspase-12

2004 ◽  
Vol 357 (2) ◽  
pp. 127-130 ◽  
Author(s):  
Junichi Hitomi ◽  
Taiichi Katayama ◽  
Manabu Taniguchi ◽  
Akiko Honda ◽  
Kazunori Imaizumi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Caspase 3 ◽  
Caspase 12

scholarly journals Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

2017 ◽  
Vol 44 (1) ◽  
pp. 133-151 ◽  
Author(s):  
Ping-Ping Gan ◽  
Yang-Ying Zhou ◽  
Mei-Zuo Zhong ◽  
Yun Peng ◽  
Li Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Chemotherapy Resistance ◽  
P53 Mutation ◽  
Mutant P53 ◽  
Homologous Protein ◽  
Caspase 12

Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs

2005 ◽  
Vol 289 (1) ◽  
pp. G54-G63 ◽  
Author(s):  
Farah Esfandiari ◽  
Jesus A. Villanueva ◽  
Donna H. Wong ◽  
Samuel W. French ◽  
Charles H. Halsted
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Fatty Acid Synthase ◽  
Hepatic Injury ◽  
Folate Deficiency ◽  
Signal Pathways ◽  
Mrna Levels ◽  
Caspase 12 ◽  
Ethanol Feeding ◽  
Stress Signals

Previously, we showed that feeding micropigs ethanol with a folate-deficient diet promoted the development of hepatic injury while increasing hepatic levels of homocysteine and S-adenosylhomocysteine (SAH) and reducing the level of S-adenosylmethionine (SAM) and the SAM-to-SAH ratio. Our present goals were to evaluate mechanisms for hepatic injury using liver specimens from the same micropigs. The effects of ethanol feeding or folate-deficient diets, singly or in combination, on cytochrome P-450 2E1 (CYP2E1) and signal pathways for apoptosis and steatosis were analyzed using microarray, real-time PCR, and immunoblotting techniques. Apoptosis was increased maximally by the combination of ethanol feeding and folate deficiency and was correlated positively to liver homocysteine and SAH. Liver CYP2E1 and the endoplasmic reticulum stress signals glucose-regulated protein 78 (GRP78), caspase 12, and sterol regulatory element binding protein-1c (SREBP-1c) were each activated in pigs fed folate-deficient or ethanol diets singly or in combination. Liver mRNA levels of CYP2E1, GRP78, and SREBP-1c, and protein levels of CYP2E1, GRP78, nuclear SREBP, and activated caspase 12 each correlated positively to liver levels of SAH and/or homocysteine and negatively to the SAM-to-SAH ratio. The transcripts of the lipogenic enzymes fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase were elevated in the ethanol-fed groups, and each was positively correlated to liver homocysteine levels. The induction of abnormal hepatic methionine metabolism through the combination of ethanol feeding with folate deficiency is associated with the activation of CYP2E1 and enhances endoplasmic reticulum stress signals that promote steatosis and apoptosis.

scholarly journals High doses of dexamethasone induce endoplasmic reticulum stress-mediated apoptosis by promoting calcium ion influx-dependent CHOP expression in osteoblasts

2021 ◽  
Author(s):  
Yunshan Guo ◽  
Dingjun Hao ◽  
Huimin Hu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Calcium Ion ◽  
Caspase 3 ◽  
Chop Expression ◽  
Induce Endoplasmic Reticulum Stress ◽  
Caspase 12 ◽  
Ion Influx ◽  
High Doses

Abstract Background The long-term use of dexamethasone (Dex), a well-known immunosuppressant, leads to an imbalance in bone metabolism and rapid decline of bone mineral density due to apoptosis of osteoblasts. The molecular mechanisms by which Dex induces osteoblast apoptosis remain unclear. Materials and methods MC3T3-E1 cells were treated with 0, 10−8, 10−6, and 10−4 M Dex for 24 h. ATF6, phosphorylated PERK, PERK, phosphorylated IRE1, and IRE1 expression, cell apoptosis, and caspase-12 and caspase-3 activity were measured. CHOP expression and calcium ion influx rate were measured in cells treated with 0 and 10−4 M Dex for 24 h. The effect of 2-APB treatment was assessed in cells treated with 0 or 10−4 M Dex. Results Levels of ATF6 and phosphorylated PERK and IRE1 increased in a dose-dependent manner in MC3T3-E1 cells treated with 10−8, 10−6, and 10−4 M Dex, compared to the control group (P < 0.05). Cells treated with 10−6 and 10−4 M Dex had significantly increased apoptotic rates and caspase-12 and caspase-3 activities (P < 0.05). Cells treated with 10−4 M Dex had significantly increased CHOP levels and calcium ion influx rates (P < 0.05). Combined treatment with 10−4 M Dex and 2-APB abrogated the observed increases in cell apoptosis and caspase-12 and caspase-3 activities (P < 0.05). Conclusions High doses of Dex induce CHOP expression by promoting calcium ion influx-dependent induction of ATF6, phosphorylated PERK and phosphorylated IRE1, which induce endoplasmic reticulum stress-mediated apoptosis in osteoblasts. 2-APB protects the osteoblasts from the effects of Dex, preventing endoplasmic reticulum stress-mediated apoptosis.

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