scholarly journals Eicosapentaenoic Acid-Induced Autophagy Attenuates Intervertebral Disc Degeneration by Suppressing Endoplasmic Reticulum Stress, Extracellular Matrix Degradation, and Apoptosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Lin ◽  
Libin Ni ◽  
Cheng Teng ◽  
Zhao Zhang ◽  
Long Wu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Intervertebral Disc ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Protective Effects ◽  
Ecm Degradation

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), but there is still a lack of effective therapy. Multiple studies have reported that endoplasmic reticulum (ER) stress and extracellular matrix (ECM) degradation exert an enormous function on the occurrence and development of IDD. Autophagy can effectively repair ER stress and maintain ECM homeostasis. Eicosapentaenoic acid (EPA) can specifically induce autophagy. The purpose of this study is to demonstrate that EPA can promote autophagy, reduce ECM degradation and ER stress in vitro, thereby reducing cell apoptosis, and the protective effects of EPA in an IDD-rat model in vivo. Western blot and immunofluorescence were used to detect the autophagic flux, ER stress, ECM degradation, and apoptosis in nucleus pulposus cells (NPCs) treated by EPA. We also used puncture-induced IDD rats as experimental subjects to observe the therapeutic effect of EPA on IDD. Our findings indicated that EPA can effectively improve the autophagy activity in NPCs, inhibit the endoplasmic reticulum stress process, reduce the degree of cell apoptosis, and exert protective effects on the anabolism and catabolism of ECM. In addition, in vivo investigations demonstrated that EPA ameliorated the progression of puncture-induced IDD in rats. In conclusion, this study revealed the intrinsic mechanisms of EPA’s protective role in NPCs and its potential therapeutic significance for the treatment of IDD.

scholarly journals Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-27 ◽  
Author(s):  
Liang Kang ◽  
Qian Xiang ◽  
Shengfeng Zhan ◽  
Yu Song ◽  
Kun Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Autophagic Flux ◽  
Ecm Degradation

Oxidative stress-induced mitochondrial dysfunction and nucleus pulposus (NP) cell apoptosis play crucial roles in the development of intervertebral disc degeneration (IDD). Increasing studies have shown that interventions targeting impaired autophagic flux can maintain cellular homeostasis by relieving oxidative damage. Here, we investigated the effect of curcumin (CUR), a known autophagy activator, on IDD in vitro and in vivo. CUR suppressed tert-butyl hydroperoxide- (TBHP-) induced oxidative stress and mitochondrial dysfunction and thereby inhibited human NP cell apoptosis, senescence, and ECM degradation. CUR treatment induced autophagy and enhanced autophagic flux in an AMPK/mTOR/ULK1-dependent manner. Notably, CUR alleviated TBHP-induced interruption of autophagosome-lysosome fusion and impairment of lysosomal function and thus contributed to the restoration of blocked autophagic clearance. These protective effects of CUR in TBHP-stimulated human NP cells resembled the effects produced by the autophagy inducer rapamycin, but the effects were partially eliminated by 3-methyladenine- and compound C-mediated inhibition of autophagy initiation or chloroquine-mediated obstruction of autophagic flux. Lastly, CUR also exerted a protective effect against puncture-induced IDD progression in vivo. Our results showed that suppression of excessive ROS production and mitochondrial dysfunction through enhancement of autophagy coupled with restoration of autophagic flux ameliorated TBHP-induced human NP cell apoptosis, senescence, and ECM degradation. Thus, maintenance of the proper functioning of autophagy represents a promising therapeutic strategy for IDD, and CUR might serve as an effective therapeutic agent for IDD.

scholarly journals NOD1/NOD2 and RIP2 Regulate Endoplasmic Reticulum Stress-Induced Inflammation during Chlamydia Infection

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Oanh H. Pham ◽  
Bokyung Lee ◽  
Jasmine Labuda ◽  
A. Marijke Keestra-Gounder ◽  
Mariana X. Byndloss ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Inflammatory Response ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Young Women ◽  
The United States ◽  
Chlamydia Infection ◽  
Er Stress Response

ABSTRACT The inflammatory response to Chlamydia infection is likely to be multifactorial and involve a variety of ligand-dependent and -independent recognition pathways. We previously reported the presence of NOD1/NOD2-dependent endoplasmic reticulum (ER) stress-induced inflammation during Chlamydia muridarum infection in vitro, but the relevance of this finding to an in vivo context is unclear. Here, we examined the ER stress response to in vivo Chlamydia infection. The induction of interleukin 6 (IL-6) production after systemic Chlamydia infection correlated with expression of ER stress response genes. Furthermore, when tauroursodeoxycholate (TUDCA) was used to inhibit the ER stress response, an increased bacterial burden was detected, suggesting that ER stress-driven inflammation can contribute to systemic bacterial clearance. Mice lacking both NOD1 and NOD2 or RIP2 exhibited slightly higher systemic bacterial burdens after infection with Chlamydia. Overall, these data suggest a model where RIP2 and NOD1/NOD2 proteins link ER stress responses with the induction of Chlamydia-specific inflammatory responses. IMPORTANCE Understanding the initiation of the inflammatory response during Chlamydia infection is of public health importance given the impact of this disease on young women in the United States. Many young women are chronically infected with Chlamydia but are asymptomatic and therefore do not seek treatment, leaving them at risk of long-term reproductive harm due to inflammation in response to infection. Our manuscript explores the role of the endoplasmic reticulum stress response pathway initiated by an innate receptor in the development of this inflammation.

scholarly journals Endoplasmic Reticulum Stress Is Involved in Baicalin Protection on Chondrocytes From Patients With Osteoarthritis

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881063 ◽  
Author(s):  
Jiangang Cao ◽  
Yu Zhang ◽  
Tianyi Wang ◽  
Bo Li
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Viability ◽  
Er Stress ◽  
Messenger Rna ◽  
Cell Counting ◽  
Protective Effects ◽  
Gene Expressions ◽  
Protein Levels

Osteoarthritis (OA) affects elderly population worldwide and endoplasmic reticulum (ER) stress is known to be positively correlated with OA development. Previous reports prove the cytoprotective effects of baicalin on chondrocytes, whereas the mechanisms are hardly reported. Hence, we aimed to investigate the links between OA, ER stress, and baicalin. Chondrocytes from patients with OA were subjected to H2O2 treatment with or without baicalin pretreatment, and cell viability was assessed via Cell Counting Kit-8. Messenger RNA (mRNA) amounts of apoptosis-related genes (Bax, Bcl-2, and Caspase-3), extracellular matrix (ECM)-related genes (Collange I, Collange II, Aggrecan, and Sox9) and ER stress hallmarks (binding immunoglobulin protein [BiP] C/EBP homologous protein [CHOP]) were evaluated via quantitative real-time PCR. Bax, Bcl-2, BiP, and CHOP protein levels were analyzed via Western blot. Baicalin suppressed the changes in cell viability and apoptosis-related gene expressions caused by H2O2. Reactive oxygen species and glutathione/oxidized glutathione assay showed that H2O2 enhanced oxidative stress. Baicalin suppressed H2O2-induced downregulation of mRNA expression of ECM-related genes. Moreover, baicalin reduced H2O2-stimulated increase in oxidative stress and the expression of ER stress hallmarks. Endoplasmic reticulum stress inducer abolished the protective activities, whereas ER stress inhibitor did not exhibit extra protective effects. Baicalin pretreatment protected patient-derived chondrocytes from H2O2 through ER stress inhibition.

scholarly journals Both endoplasmic reticulum and mitochondria are involved in disc cell apoptosis and intervertebral disc degeneration in rats

AGE ◽  
2009 ◽  
Vol 32 (2) ◽  
pp. 161-177 ◽  
Author(s):  
Chang-Qing Zhao ◽  
Yue-Hui Zhang ◽  
Sheng-Dan Jiang ◽  
Lei-Sheng Jiang ◽  
Li-Yang Dai
Keyword(s):  
Endoplasmic Reticulum ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Disc Cell

Fish oil supplementation inhibits endoplasmic reticulum stress and improves insulin resistance: involvement of AMP-activated protein kinase

2017 ◽  
Vol 8 (4) ◽  
pp. 1481-1493 ◽  
Author(s):  
Wenqi Yang ◽  
Xu Chen ◽  
Ming Chen ◽  
Yanping Li ◽  
Qing Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Endoplasmic Reticulum Stress ◽  
Fish Oil ◽  
Er Stress ◽  
Protective Effects ◽  
Ampk Activation ◽  
Amp Activated Protein Kinase ◽  
Fish Oil Supplementation

ER stress inhibition through AMPK activation may explain the protective effects of fish oil against HFD-induced insulin resistance.

scholarly journals Tunicamycin-Induced Endoplasmic Reticulum Stress Promotes Breast Cancer Cell MDA-MB-231 Apoptosis through Inhibiting Wnt/β-Catenin Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhongsheng You ◽  
Linkang He ◽  
Nianlong Yan
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Triple Negative ◽  
Basic Mechanism ◽  
Chemotherapy Treatment ◽  
Related Proteins

Triple negative breast cancer (TNBC) has significantly threatened human health. Many aspects of TNBC are closely related to Wnt/β-catenin pathway, and cell apoptosis induced by endoplasmic reticulum stress (ER stress) in TNBC may act as a potential target of non-chemotherapy treatment. However, how ER stress interacts with this pathway in TNBC has not yet been understood. Here, the tunicamycin and LiCl have been applied to MDA-MB-231. The related proteins’ expression was measured by western blotting. Moreover, acridine orange/ethidium bromide (AO/EB) staining was applied to test the apoptosis degree of the cells, and cell viability was tested by MTT experiment. Then, we found the ER stress and apoptosis degree of MDA-MB-231 were induced after treatment with tunicamycin. Besides, tunicamycin dose dependently inhibited both Wnt/β-catenin pathway and cells viability. Licl, an activator of Wnt/β-catenin signaling pathway, could significantly inhibit cell apoptosis. In conclusion, our study found that the activation of ER stress could promote the MDA-MB-231 apoptosis by repressing Wnt/β-catenin pathway, which provides some promising prospects and basic mechanism to the further research.

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