scholarly journals Shengmai Injection Improved Doxorubicin-Induced Cardiomyopathy by Alleviating Myocardial Endoplasmic Reticulum Stress and Caspase-12 Dependent Apoptosis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Chen ◽  
Yong Tang ◽  
Yin Xiang ◽  
Yu-Quan Xie ◽  
Xiao-Hong Huang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Chinese Medicine ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Heart Function ◽  
Shengmai Injection ◽  
Heart Damage ◽  
Myocardial Apoptosis ◽  
Caspase 12 ◽  
Dependent Pathway

Background.Apoptosis plays vital roles in the progression of doxorubicin-induced cardiomyopathy (DOX-CM). Endoplasmic reticulum stress (ER stress) could induce specific apoptosis by caspase-12 dependent pathway. Shengmai Injection (SMI), a famous Traditional Chinese Medicine, could alleviate the heart damage via inhibiting myocardial apoptosis. However, it is unknown whether SMI can alleviate ER stress and its specific apoptosis in the setting of DOX-CM.Objective.To explore the effects of SMI on heart function, myocardial ER stress, and apoptosis of DOX-CM rats.Methods.Rats with DOX-CM were treated by SMI. Heart function was assessed by echocardiography and brain natriuretic peptide. Myocardial apoptosis was detected by TUNEL assay. ER stress was assessed by detecting the expressions of GRP78 and caspase-12.Results.At the end of eight-week, compared to control, significant heart dysfunction happened in DOX group. The ratio of apoptotic cardiomyocytes and the expressions of GRP78 and caspase-12 increased significantly (P<0.05). Compared to DOX group, the apoptotic ratio and the expressions of GRP78 and caspase-12 significantly decreased in DOX + SMI group (P<0.05), accompanied with improved heart function.Conclusion.SMI could alleviate myocardial ER stress and caspase-12 dependent apoptosis, which subsequently helped to improve the heart function of rats with DOX-CM.

Cardiomyocyte apoptosis in autoimmune cardiomyopathy: mediated via endoplasmic reticulum stress and exaggerated by norepinephrine

2007 ◽  
Vol 293 (3) ◽  
pp. H1636-H1645 ◽  
Author(s):  
Weike Mao ◽  
Shuji Fukuoka ◽  
Chikao Iwai ◽  
Jiahao Liu ◽  
Virendra K. Sharma ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
P38 Mapk ◽  
Adrenergic Receptor ◽  
Heart Function ◽  
Systolic Dysfunction ◽  
Biologically Active ◽  
Neonatal Cardiomyocytes ◽  
Caspase 12 ◽  
Myocyte Apoptosis

Evidence suggests that the autoimmune cardiomyopathy produced by a peptide corresponding to the sequence of the second extracellular loop of the β1-adrenergic receptor (β1-ECII) is mediated via a biologically active anti-β1-ECII antibody, but the mechanism linking the antibody to myocyte apoptosis and cardiac dysfunction has not been well elucidated. Since the β1-ECII autoantibody is a partial β1-agonist, we speculate that the cardiomyopathy is produced by the β1-receptor-mediated stimulation of the CaMKII-p38 MAPK-ATF6 signaling pathway and endoplasmic reticulum (ER) stress, and that excess norepinephrine (NE) exaggerates the cardiomyopathy. Rabbits were randomized to receive β1-ECII immunization, sham immunization, NE pellet, or β1-ECII immunization plus NE pellet for 6 mo. Heart function was measured by echocardiography and catheterization. Myocyte apoptosis was determined by terminal deoxytransferase-mediated dUTP nick-end labeling and caspase-3 activity, whereas CaMKII, MAPK family (JNK, p38, ERK), and ER stress signals (ATF6, GRP78, CHOP, caspase-12) were measured by Western blot, immunohistochemistry, and kinase activity assay. β1-ECII immunization produced progressive LV dilation, systolic dysfunction, and myocyte apoptosis. These changes were associated with activation of GRP78 and CHOP and increased cleavage of caspase-12, as well as increased CaMKII activity, increased phosphorylation of p38 MAPK, and nucleus translocation of cleaved ATF6. NE pellet produced additive effects. In addition, KN-93 and SB 203580 abolished the induction of ER stress and cell apoptosis produced by the β1-ECII antibody in cultured neonatal cardiomyocytes. Thus ER stress occurs in autoimmune cardiomyopathy induced by β1-ECII peptide, and this is enhanced by increased NE and caused by activation of the β1-adrenergic receptor-coupled CaMKII, p38 MAPK, and ATF6 pathway.

Abstract 38: Endoplasmic Reticulum Stress Pathway-mediated Apoptosis is Involved in Ang II Induced Abdominal Aortic Aneurysm

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Yanwen Qin ◽  
Xu Cao ◽  
Ou Liu ◽  
Huihua Li ◽  
Hongjia Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Apolipoprotein E ◽  
Er Stress ◽  
Aortic Aneurysms ◽  
Aortic Diameter ◽  
Ang Ii ◽  
Caspase 12 ◽  
Abdominal Aortic ◽  
Deficient Mice

Backgroud— Abdominal aortic aneurysms (AAA) represent a unique and dramatic example of vessel wall remodeling characterized by degeneration of the elastic media. Apoptosis of vascular smooth muscle cells plays an important role in the pathogenesis of AAA. However, the potential mechanism remains poorly understood. Endoplasmic reticulum stress (ER stress)-induced apoptosis has been proved to be one of the important pathogenesis of cardiovascular disease. However, whether ER stress is involved in AAA is still not known. We assessed the hypothesis that ER-associated apoptosis is involved in Angiotensin II (Ang II)-induced AAA in apolipoprotein E-deficient mice. Methods and Results— Mice were infused with Ang II (1000 ng/kg per minute) with or without ER stress inhibitor (taurine-conjugated ursodeoxycholic acid) for 4 weeks. Mice infused with Ang II displayed an increase in aortic diameter. Detection of apoptosis was performed with the TUNEL assay. We performed Western blot and Real-time PCR to analyze indicators of ER molecule chaperone and ER-associated apoptosis. Glucose Regulated Proteins 78 and 94 (GRP78/BiP and GRP94), the ER chaperone, were up-regulated significantly in AAA compared to control. Furthermore, the hallmarks of ER-associated apoptosis, C/EBP homologous protein (CHOP), caspase-12 and PERK-eIF2-ATF4 signaling pathway were found to have activated in the AAA. The inhibition of ER stress significantly decreased maximal aortic diameter by 31% and abdominal aortic weight by 35% ( P <0.05, respectively). ER stress inhibitor also reduced GRP 78, CHOP and caspase-12 expression ( P <0.05, respectively). Taken together, these results suggested that apoptosis induced by ER stress may contribute to the development of AAA. Conclusions— ER stress response is involved in the pathogenesis of Ang II induced AAA in apolipoprotein E-deficient mice. ER stress inhibition attenuates AAA formation during Ang II infusion in apolipoprotein E-deficient mice. Therefore, ER stress could be a potential target for AAA.

scholarly journals Arabidopsis GAAPs interacting with MAPR3 modulate the IRE1-dependent pathway upon endoplasmic reticulum stress

2019 ◽  
Vol 70 (21) ◽  
pp. 6113-6125 ◽  
Author(s):  
Manli Zhu ◽  
Xiaohan Tang ◽  
Zhiying Wang ◽  
Wenqi Xu ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Autophagy Pathway ◽  
Dependent Pathway

Arabidopsis GAAP1 and GAAP3 interacted with MAPR3. MAPR3 and the interaction between GAAPs and MAPR3 mitigated ER stress through modulation of RIDD and the autophagy pathway dependent on association with IRE1B.

scholarly journals Tang-Luo-Ning, a Traditional Chinese Medicine, Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis of Schwann Cells under High Glucose Environment

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Weijie Yao ◽  
Xinwei Yang ◽  
Jiayue Zhu ◽  
Biane Gao ◽  
Renhui Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Peripheral Neuropathy ◽  
Chinese Medicine ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Schwann Cells ◽  
Marker Protein ◽  
Definite Effect ◽  
Induced Apoptosis ◽  
Apoptosis Marker

Tang-Luo-Ning (TLN) has a definite effect in the clinical treatment of diabetic peripheral neuropathy (DPN). Schwann cells (SCs) apoptosis induced by endoplasmic reticulum stress (ER stress) is one of the main pathogeneses of DPN. This study investigates whether TLN can inhibit SCs apoptosis by inhibiting ER stress-induced apoptosis. Our previous researches have demonstrated that TLN could increase the expression of ER stress marker protein GRP78 and inhibited the expression of apoptosis marker protein CHOP in ER stress. In this study, the results showed that TLN attenuated apoptosis by decreasing Ca2+ level in SCs and maintaining ER morphology. TLN could decrease downstream proteins of CHOP including GADD34 and Ero1α, while it increased P-eIF2α and decreased the upstream proteins of CHOP including P-IRE1α/IRE1α and XBP-1, thereby reducing ER stress-induced apoptosis.

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

scholarly journals Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4538
Author(s):  
Helena Kratochvílová ◽  
Miloš Mráz ◽  
Barbora J. Kasperová ◽  
Daniel Hlaváček ◽  
Jakub Mahrík ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mrna Expression ◽  
Coronary Atherosclerosis ◽  
Stress Genes ◽  
Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

scholarly journals RHBDL4 protects against endoplasmic reticulum stress by regulating the morphology and distribution of ER sheets

2021 ◽  
Author(s):  
Viorica Liebe Lastun ◽  
Matthew Freeman
Keyword(s):  
Cell Cycle ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Liver Steatosis ◽  
Physiological Role ◽  
Cell Types ◽  
Rhomboid Protease ◽  
Rapid Changes

In metazoans, the architecture of the endoplasmic reticulum (ER) differs between cell types, and undergoes major changes through the cell cycle and according to physiological needs. Although much is known about how the different ER morphologies are generated and maintained, especially the ER tubules, how context dependent changes in ER shape and distribution are regulated and the factors involved are less characterized. Here, we show that RHBDL4, an ER-resident rhomboid protease, modulates the shape and distribution of the ER, especially under conditions that require rapid changes in the ER sheet distribution, including ER stress. RHBDL4 interacts with CLIMP-63, a protein involved in ER sheet stabilisation, and with the cytoskeleton. Mice lacking RHBDL4 are sensitive to ER stress and develop liver steatosis, a phenotype associated with unresolved ER stress. Our data introduce a new physiological role of RHBDL4 and also imply that this function does not require its enzymatic activity.

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