scholarly journals Guanxinkang Decoction Exerts Its Antiatherosclerotic Effect Partly through Inhibiting the Endoplasmic Reticulum Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Hao Wang ◽  
Zhi-Min Zheng ◽  
Bu-Lang Gao
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
Dose Group ◽  
Control Group ◽  
Blank Control Group ◽  
Apoptosis Rate ◽  
Model Control ◽  
Model Control Group ◽  
Antiatherosclerotic Effect

Purpose. To investigate the antiatherosclerotic effect of Guanxinkang (GXK) decoction on the apoptosis, mitochondrial membrane potential (MMP), and endoplasmic reticulum stress (ERS) of human umbilical vein endothelial cells (HUVEC) pretreated with homocysteinemia (HCY).Materials and Methods. HUVEC were randomly divided into 5 groups: (1) blank control group (control), (2) model control group (model), (3) GXK low dose group, (4) GXK medium dose group, and (5) GXK high dose group. For the three GXK groups, HCY was given to reach the concentration of 3.0 mmol/L after HUVEC had been incubated with rabbit serum containing GXK for two hours. At 3, 6, 12, and 24 h after HCY had been incubated with the cells, the HUVEC were collected for test of the apoptosis rate, MMP, and GRP78 protein (reflecting ERS).Results. In the model control group, the apoptosis rate and GRP 78 protein expression of HUVEC significantly increased (P<0.05), while MMP significantly decreased (P<0.05) compared with the blank control group. After GXK treatment of medium and high doses, the apoptosis rate and the GRP 78 protein expression significantly (P<0.05) decreased, while MMP significantly increased (P<0.05) in a time-dependent manner compared with the model control group.Conclusion. GXK can antagonize the injury of HUVEC caused by HCY and the antagonism effect increases with the concentration and treatment duration of GXK, with the possible mechanism of GXK antagonism being through inhibiting ERS caused by HCY.

scholarly journals Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yang Cao ◽  
Meng-fei Zhuang ◽  
Ying Yang ◽  
Shu-wu Xie ◽  
Jin-gang Cui ◽  
...  
Keyword(s):  
Western Blot ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
Expression Levels ◽  
Model Control ◽  
Model Control Group ◽  
Preliminary Study ◽  
Ectopic Endometrium

In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

scholarly journals Protective effects and mechanisms of microRNA-182 on oxidative stress in RHiN

2019 ◽  
Vol 14 (1) ◽  
pp. 400-409
Author(s):  
Lihua Li ◽  
Wenna Peng ◽  
Xiangrong Tian
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Survival Rate ◽  
Control Group ◽  
Mrna Levels ◽  
Protective Effects ◽  
Apoptosis Rate ◽  
Model Control ◽  
Model Control Group ◽  
Phosphoinositide 3 Kinase

AbstractTo explore protective effects and related mechanisms of microRNA-182 (miR-182) on oxidative stress in rat hippocampal neurons (RHiN), RHiN cells. As the results, the survival rate and superoxide dismutase levels in H2O2 group were significantly lower than H2O2+miR-182 group (all P<0.05). The malondialdehyde levels and apoptosis rate in H2O2+miR-182 group were significantly lower than H2O2 group (all P<0.05). The mRNA levels and expression levels of mTOR and PI3K in H2O2+miR-182 group were higher than those in H2O2 group (both P<0.05). The experiment of cerebral ischemic oxidative stress model rats showed that the survival rate, apoptosis rate, malondialdehyde and superoxide dismutase levels in miR-182 group were better than model control group. The positive staining intensity of phosphoinositide 3-kinase (mTOR) and phosphoinositide 3-kinase (PI3K) in model control group were significantly lower than miR-182 group (all P<0.05). Increased levels of miR-182 can reduce the damage of H2O2 treatments in RHiN cells. Oxidative stress is decreased in the neuronal cells possibly by activation of the PI3K-AKT-mTOR pathway.

Effect And Mechanism of Endoplasmic Reticulum Stress Induced By Tunicamycin In Trabecular Meshwork Cells

2021 ◽  
Author(s):  
Yuyu Wu ◽  
Xiaorui Wang ◽  
Guangqian Huang ◽  
Tingting Ou
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Trabecular Meshwork ◽  
Caspase 3 ◽  
Expression Level ◽  
Control Group ◽  
Apoptosis Rate ◽  
Trabecular Meshwork Cells ◽  
The Difference ◽  
Experimental Group

Abstract Objective: To explore the role of endoplasmic reticulum stress in apoptosis of trabecular meshwork cellsMethods: Human trabecular meshwork cells(HTMCs) were cultured in vitro. When the cells grew to logarithmic phase, they were digested and resuspended, and then cultured in 96-well plate. When the cells are close to fusion, the culture is continued for 24h in a serum-free medium, The HTMCs were treated with different concentrations of tunicamycin (0mg/L, 1.25mg/L, 2.5mg/L, 5mg/L, 10mg/L, and 20mg/L) for different durations (0h, 6h, 12h, 24h, 36h, and 48h). The cytoactive was detected by CCK-8, and the optimal intervention concentration of tunicamycin was determined. Then we use the 5mg/L tunicamycin to interfere with HTMCs for different durations (0h, 6h, 12h, and 24h). The apoptotic rate was detected by flow cytometry, and the expression levels of GRP78, CHOP, Bcl-2 and Caspase-3 were detected by RT-PCR and Western blot. Results: The number of RGCs in IRI group was significantly lower than that in NC group (P < 0.05), demonstrated by HE staining. Western blotting results indicated that the protein expression of LC3 and Beclin-1 in the IRI group were significantly elevated compared with those in the NC group (P < 0.05). However, with 3-MA treatment, the number of RCGs in 3-MA treated-IRI group was elevated and protein levels of LC3, Beclin-1 were downregultated, compared with those in the IRI group (P < 0.05). Further immunohistochemistry staining and Western blot showed that 3-MA treated-IRI group presented downregulated Caspase-3 and upregulated Bcl-2 protein expression with comparison of IRI group (P < 0.05). CCK-8 results showed that the inhibition rate of HTMCs increased with the increase of tunicamycin concentration and duration of intervention. When the concentration of tunicamycin was 1.25mg / L and 2.5mg / L, there was no significant difference in cell inhibition rate compared with the control group (P> 0.05). When the concentration of tunicamycin was 5mg / L and the duration of action was 12h or more, the cells showed significant inhibition, of which the cell inhibition rates at 12h, 24h, 36h and 48h were (21.11 ± 1.23)% and (31.34 ± 0.86, respectively) )%, (44.37 ± 1.01)%, (51.47 ± 0.36)%, compared with the 0h group, the differences were statistically significant (P <0.05).The results of flow cytometry suggest that with the increase of the time of action of tunicamycin, the early apoptosis rate and the late apoptosis rate of the cells increase significantly. Compared with the control group, the experimental group with different intervention durations had significantly higher early cell apoptosis rate and late cell apoptosis rate, and the difference was statistically significant (P <0.05). RT-PCR test results indicated that the expression levels of GRP-78, CHOP, and Caspase-3 mRNA in the experimental groups (6h, 12h, and 24h) with different intervention durations were all increased compared with the control group, and the difference was statistically significant ( P <0.05); BCL-2 mRNA expression in the experimental groups (6h, 12h, 24h) with different intervention durations was reduced compared with the control group, and the difference was statistically significant (P<0.05).Western blot test results showed that compared with the control group, GRP-78 and CHOP protein expressions of the experimental groups (6h, 12h, 24h) with different intervention durations increased, the difference was statistically significant (P <0.05). Compared with the control group, the expression level of Caspase-3 protein increased in the 12h group and the difference was statistically significant (P <0.05). The increase in the expression level of the remaining experimental group was not obvious, and the difference was not statistically significant (P> 0.05); 24h Compared with the control group, the expression level of BCL-2 protein was significantly reduced, the difference was statistically significant (P <0.05), the expression level of BCL-2 protein in the remaining experimental group was not significantly reduced, and the difference was not statistically significant (P> 0.05). Conclusion: Tunicamycin can increase the expression of endoplasmic reticulum stress proteins in trabecular meshwork cells and induce apoptosis. Our study demonstrated that endoplasmic reticulum stress played an important role in the apoptosis of trabecular meshwork cells.

scholarly journals Albendazole reduces endoplasmic reticulum stress induced by Echinococcus multilocularis in mice

2021 ◽  
Author(s):  
Michael Weingartner ◽  
Fadi Jebbawi ◽  
Junhua Wang ◽  
Simon Stücheli ◽  
Bruno Gottstein ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
Echinococcus Multilocularis ◽  
Liver Tissue ◽  
Alveolar Echinococcosis ◽  
Surgical Intervention ◽  
Fatal Disease ◽  
Unfolded Protein ◽  
Protein Response

AbstractBackgroundEchinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with relatively frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice.MethodsE. multilocularis- and mock-infected C57BL/6 mice were subdivided six weeks after infection into vehicle and albendazole (ABZ) treated groups. Eight weeks later, liver tissue was collected to examine mRNA, microRNA (miR) and protein expression of UPR- and ERS-related genes.ResultsE. multilocularis infection upregulated UPR- and ERS-related proteins, including ATF6, CHOP, GRP78, ERP72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed the increased ATF6 and calreticulin protein expression, tended to reverse increased CHOP, GRP78, ERP72 and H6PD expression, and decreased ATF4 and IRE1α expression to levels seen in mock-infected mice. The expression of miR-146a-5p (downregulated by IRE1α) and miR-1839-5p (exhibiting a unique target site in the IRE1α 3’UTR) were significantly increased in E. multilocularis infected mice, an effect reversed by ABZ treatment. Other miRs analyzed were not altered in E. multilocularis infected mice.Conclusions and SignificanceAE causes UPR activation and ERS in mice. The E. multilocularis-induced ERS was ameliorated by ABZ treatment, indicating its effectiveness to inhibit parasite proliferation and downregulate its activity status. ABZ itself did not affect UPR in control mice. Identified miR-146a-5p and miR-1839-5p might represent biomarkers of E. multilocularis infection. Modulation of UPR and ERS, in addition to ABZ administration, could be exploited to treat E. multilocularis infection.Author summaryAlveolar echinococcosis is a zoonotic disease caused by the fox tapeworm Echinococcus multilocularis. Treatment of this fatal disease is limited to surgical intervention, preferably radical curative surgery if possible, and the use of parasitostatic benzimidazoles. It is not yet fully understood how the parasite can remain in the host’s tissue for prolonged periods, complicating the development of therapeutic applications. This work investigated an involvement of the unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection and upon treatment with albendazole (ABZ) in mice. The results revealed increased expression levels of the ERS sensor ATF6 and of downstream target genes in liver tissue of E. multilocularis- compared to mock-infected mice. Additionally, H6PD, generating NADPH within the endoplasmic reticulum, and the lectin-chaperone calreticulin were increased in E. multilocularis infected liver tissue while the expression of the ERS associated genes ATF4 and IRE1α were decreased. The miR-1839-5p and miR-146-p, linked to IRE1α, were elevated upon E. multilocularis infection, offering potential as novel biomarkers of alveolar echinococcosis. The observed gene expression changes were at least partially reversed by ABZ treatment. Whether modulation of UPR and ERS targets can improve the therapy of alveolar echinococcosis remains to be investigated.

scholarly journals Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shanyong Yi ◽  
Weibo Shi ◽  
Min Zuo ◽  
Songjun Wang ◽  
Rufei Ma ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Pc12 Cells ◽  
Neuronal Injury ◽  
Immunofluorescence Staining ◽  
High Concentration ◽  
Flow Cytometry Assay ◽  
Apoptosis Rate ◽  
Amino Terminal

Objective. The present study selected PC12 cells to construct a neuronal injury model induced by glucocorticoids (GC) in vitro, aiming to explore whether the endoplasmic reticulum stress (ERS) PKR-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP-homologous protein (CHOP) and inositol requirement 1 (IRE1)-apoptosis signal regulating kinase 1 (ASK1)-C-Jun amino-terminal kinase (JNK) signaling pathways are associated with the neuronal injury process induced by GC and provide morphological evidence. Methods. Cell models with different doses and different durations of GC exposure were established. The viability of PC12 cells was detected by the CCK-8 assay, and the apoptosis rate of PC12 cells was detected by the flow cytometry assay. The expression of microtubule-associated protein 2 (Map2); glucocorticoids receptor (GR); cellular oncogene fos (C-fos); and ERS-related proteins, glucose-regulated protein 78 (GRP78), p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP, was observed by immunofluorescence staining. Results. The results of immunofluorescence staining showed that PC12 cells abundantly expressed Map2 and GR. The CCK-8 assay revealed that high-concentration GC exposure significantly inhibited the cell viability of PC12 cells. The flow cytometry assay indicated that high-concentration GC exposure significantly increased the apoptosis rate of PC12 cells. Immunofluorescence staining showed that GC exposure significantly increased the expression of C-fos, GRP78, p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP. Treatment with ERS inhibitor 4-phenylbutyric acid (4-PBA) and GR inhibitor RU38486 attenuated related damage and downregulated the expression of the abovementioned proteins. Conclusion. High-concentration GC exposure can significantly inhibit the viability of PC12 cells and induce apoptosis. PERK-ATF4-CHOP and IRE1-ASK1-JNK pathways are involved in the above damage process.

scholarly journals The Pathology of Morphine-Inhibited Nerve Repair and Morphine-Induced Nerve Damage Is Mediated via Endoplasmic Reticulum Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Jie Liu ◽  
Shanyong Yi ◽  
Weibo Shi ◽  
Guozhong Zhang ◽  
Songjun Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
Cortical Neurons ◽  
Nerve Repair ◽  
Pathological Changes ◽  
Dynamic Changes ◽  
Ki 67 ◽  
Newborn Neurons ◽  
Immunofluorescence Labeling

ObjectiveThe aim of the present study was to observe the pathological damage in the cerebral cortex of rats under acute morphine exposure (AME) and different durations of morphine dependence (MD), explore whether endoplasmic reticulum stress (ERS) is involved in the damage process, and assess the effect of morphine exposure on the proliferation and differentiation of newborn neurons.MethodsRat models of AME and different durations of MD were established. Pathological changes in cortical neurons were assessed by hematoxylin and eosin (H&amp;E) and thionine staining. The expression of nuclear receptor-related factor 1 (NURR1) and that of the ERS-related proteins glucose-regulated protein 78 (GRP78), p-eIF2α, activating transcription factor 6 (ATF6), and CHOP in cortical neurons was assessed by immunohistochemistry. Double immunofluorescence labeling was used to observe the expression of Ki-67.ResultsH&amp;E and thionine staining revealed that AME resulted in pyknotic changes in cortical neurons. With prolonged morphine exposure, the number of pyknotic neurons was significantly increased, the protein expression of Ki-67 and NURR1 was significantly decreased, and the protein levels of GRP78, p-eIF2α, ATF6, and CHOP showed marked dynamic changes.ConclusionAME and different durations of MD caused varying degrees of pathological changes in the cortex. Furthermore, the dynamic changes observed in ERS-related protein expression suggested that ERS may be associated with cortical injury. Different durations of MD inhibited the proliferation, differentiation, and migration of newborn neurons, which may affect the nerve repair process after injury.

Enhanced GRP78 protein expression via the IRE1α/ASK1/p38 MAPK pathway during As2O3-induced endoplasmic reticulum stress in BEAS-2B cells

Toxicology ◽  
2021 ◽  
Vol 462 ◽  
pp. 152962
Author(s):  
Jiaming Yuan ◽  
Chenjuan Yao ◽  
Jing Tang ◽  
Yingqi Liu ◽  
Chunyan Huang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
P38 Mapk Pathway

scholarly journals Recombinant α-Klotho Protein Alleviated Acute Cardiorenal Injury in a Mouse Model of Lipopolysaccharide-Induced Septic Cardiorenal Syndrome Type 5

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Xi Liu ◽  
Yangyang Niu ◽  
Xiaoqin Zhang ◽  
Yingying Zhang ◽  
Ying Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Interleukin 1 ◽  
Kidney Injury ◽  
Left Ventricular ◽  
Control Group ◽  
Renal Tubules ◽  
Protective Function ◽  
Klotho Protein

Background and Aims. Klotho is an aging-suppressor gene mainly expressed in the renal tubules. The klotho gene encodes the α-klotho protein, which has many functions. Previous studies have found that α-klotho protein has a cardiorenal protective function. α-Klotho deficiency renders the kidney more susceptible to injury and results in cardiovascular calcification and left ventricular hypertrophy in chronic kidney disease. However, the role of α-klotho in acute heart injury and acute kidney injury with sepsis remains unknown. This study aimed to investigate the effects and mechanisms of α-klotho in septic cardiorenal injury. Methods. Male 8-week-old C57BL/6 mice were randomly assigned to the control group, lipopolysaccharide (LPS; 10 mg/kg) group, LPS (10 mg/kg)+α-klotho (0.01 mg/kg) group, and LPS (10 mg/kg)+α-klotho (0.02 mg/kg) group. Recombinant α-klotho was intraperitoneally injected an hour before LPS injection. Mice were euthanized at 24 h after LPS injection. The serum troponin, brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels were measured in all groups at 24 h. Biomarkers of mice heart apoptosis, inflammation, oxidative stress, and endoplasmic reticulum stress, such as caspase-3, interleukin 1 (IL-1), reactive oxygen species (ROS), and glucose-regulated protein 78 (GRP78), were also measured. Results. α-Klotho was mainly expressed in mice kidneys and was undetectable in the control mice hearts. α-Klotho substantially decreased after LPS injection. In the LPS group, the serum troponin levels significantly increased as early as 6 h (p<0.05) after LPS injection, while the BNP, NGAL, and creatinine levels significantly increased at 24 h (p<0.05). Pretreatment with α-klotho significantly ameliorated acute cardiorenal injury. In the LPS+α-klotho (0.01 mg/kg) group, the levels of apoptosis, inflammation, and oxidative stress were decreased, while the level of endoplasmic reticulum stress was elevated. Conclusions. α-Klotho significantly alleviates acute cardiorenal injury in LPS-induced septic cardiorenal injury due to the inhibition of apoptosis, inflammation, and oxidation, as well as the regulation of endoplasmic reticulum stress levels.

The Effect of EA on the Gastric Mucosal Histology and ITF mRNA Expression in Stress-Induced Rats

2006 ◽  
Vol 34 (06) ◽  
pp. 1005-1014
Author(s):  
Xi-Ping Li ◽  
Jie Yan ◽  
Shou-Xiang Yi ◽  
Xiao-Rong Chang ◽  
Ya-Ping Lin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Water Immersion ◽  
Histological Change ◽  
Control Group ◽  
Protective Mechanism ◽  
Gastric Mucosal Lesion ◽  
Intestinal Trefoil Factor ◽  
Blank Control Group ◽  
Model Control ◽  
Stomach Meridian

This study focuses on the effect of electroacupuncture (EA) on the gastric mucosal histology and ITF (intestinal trefoil factor) mRNA in stress-related rat, and the relationship between the gastric protective mechanism of EA at acupoints of Stomach Meridian of Foot-Yangming (SMFY) group and Gallbladder Meridian of Foot-Shaoyang (GMFS) group. Forty rats were randomly divided into 4 groups: blank control group (BCG), model control group (MCG), SMFY group (EA at acupoints of SMFY for 7 days before model inducing), and GMFS group (EA at acupoints of GMFS for 7 days before model inducing). All rats (except normal group) were made model by water immersion and restriction (WRS) on day 7, then the gastric mucosal lesion index (GUI) was accessed, ITF mRNA expression of the tissue was detected by reverse- transcriptase-polymerase chain reaction (RT-PCR) method, and the histological change under light microscope was observed. As a result, the GUI value in SMFY/GMFS groups decreased significantly ( p < 0.05 or 0.01). The level of ITF mRNA expression in SMFY group was significantly higher than that in MCG ( p < 0.01), while that in GMFS group was higher than MCG but there was no statistical difference ( p < 0.05). This result may be due to the intrinsic mechanism of EA's gastric mucosal protection by the upregulation of ITF mRNA expression in gastric mucosal tissue, and the expression variance indicated the classical traditional Chinese medicine (TCM) theory "Relative Particularity between SMFY and Stomach.".

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