Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress

2016 ◽  
Vol 22 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Zhi-Yu Shi ◽  
Yue Liu ◽  
Li Dong ◽  
Bo Zhang ◽  
Meng Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Endoplasmic Reticulum ◽  
Cardiac Function ◽  
Er Stress ◽  
Rat Model ◽  
Caspase 3 ◽  
Apoptotic Pathway ◽  
Myocardial Apoptosis ◽  
Glucose Regulated Protein

Objectives: The endoplasmic reticulum (ER) stress-induced apoptotic pathway is associated with the development of acute myocardial infarction (AMI). Cortistatin (CST) is a novel bioactive peptide that inhibits apoptosis-related injury. Therefore, we investigated the cardioprotective effects and potential mechanisms of CST in a rat model of AMI. Methods: Male Wistar rats were randomly divided into sham, AMI, and AMI + CST groups. Cardiac function and the degree of infarction were evaluated by echocardiography, cardiac troponin I activity, and 2,3,5-triphenyl-2H-tetrazolium chloride staining after 7 days. The expression of CST, ER stress markers, and apoptotic markers was examined using immunohistochemistry and Western blotting. Results: Compared to the AMI group, the AMI + CST group exhibited markedly better cardiac function and a lower degree of infarction. Electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling confirmed that myocardial apoptosis occurred after AMI. Cortistatin treatment reduced the expression of caspase 3, cleaved caspase 3, and Bax (proapoptotic proteins) and promoted the expression of Bcl-2 (antiapoptotic protein). In addition, the reduced expression of glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding proteins homologous protein, and caspase 12 indicated that ER stress and the apoptotic pathway associated with ER stress were suppressed. Conclusions: Exogenous CST has a notable cardioprotective effect after AMI in a rat model in that it improves cardiac function by suppressing ER stress and myocardial apoptosis.

Exogenous hydrogen sulfide inhibits apoptosis by regulating endoplasmic reticulum stress–autophagy axis and improves myocardial reconstruction after acute myocardial infarction

2020 ◽  
Vol 52 (12) ◽  
pp. 1325-1336
Author(s):  
Yaling Li ◽  
Maojun Liu ◽  
Jiali Yi ◽  
Xiong Song ◽  
Xia Zheng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Endoplasmic Reticulum ◽  
Hydrogen Sulfide ◽  
Er Stress ◽  
Inhibitory Effect ◽  
Myocardial Apoptosis ◽  
Apoptosis Protein ◽  
Related Proteins

Abstract During acute myocardial infarction, endoplasmic reticulum (ER) stress-induced autophagy and apoptosis have been shown as important pathogeneses of myocardial reconstruction. Importantly, hydrogen sulfide (H2S), as a third endogenous gas signaling molecule, exerts strong cytoprotective effect on anti-ER stress, autophagy regulation and antiapoptosis. Here, we showed that H2S treatment inhibits apoptosis by regulating ER stress–autophagy axis and improves myocardial reconstruction after acute myocardial infarction. We found that H2S intervention improved left ventricle function, reduced glycogen deposition in myocardial tissue mesenchyme, and inhibited apoptosis. Moreover, the expressions of fibrosis indicators (Col3a1 and Col1a2), ER stress-related proteins (CHOP and BIP/ERP78), autophagy-related proteins (Beclin and ATG5), apoptosis protein (Bax), as well as fibrosis protein Col4a3bp were all decreased after treatment with H2S. H2S administration also maintained MMP/TIMP balance. Mechanistically, H2S activated the PI3K/AKT signaling pathway. In addition, H2S treatment also reduced the expressions of ER stress–related proteins, autophagy-related proteins, and apoptins in in vitro experiments. Interestingly, activation of ER stress–autophagy axis could reverse the inhibitory effect of H2S on myocardial apoptosis. Altogether, these results suggested that exogenous H2S suppresses myocardial apoptosis by blocking ER stress–autophagy axis, which in turn reverses cardiac remodeling after myocardial infarction.

scholarly journals Down-modulation of endoplasmic reticulum stressinitiated apoptosis by huperzine A in isoproterenolprovoked myocardial infarction rat model: Role of Nrf2/HO- 1 signaling axis

2020 ◽  
Vol 19 (8) ◽  
pp. 1685-1691
Author(s):  
Zhongkui Li ◽  
Lufang Gao ◽  
Daokang Xiang ◽  
Wenbo Liu
Keyword(s):  
Myocardial Infarction ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Rat Model ◽  
B Cell Lymphoma ◽  
Huperzine A ◽  
Calcium Handling ◽  
Heme Oxygenase 1 ◽  
Caspase 12 ◽  
Stress Parameters

Purpose: To investigate the myocardial protective effect of huperzine A (HPA), a sesquiterpene alkaloid, in a rat model of isoproterenol (ISP)- provoked MI and ER stress.Methods: Three groups of rats were used: control, ISP and ISP+HPA groups. The following indices were assayed using standard protocols: oxidative stress parameters, including NADPH oxidase 4 (NOX4), reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1); indices of calcium homeostasis, namely, sarcoplasmic and endoplasmic reticulum calcium ATPase isoform 2a (SERCA2a); ER stress parameters, viz, protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), glucose-regulated protein 78 (GRP78), and C/EBP homologous protein (CHOP); and indices of apoptosis, i.e., B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-12].Results: Oxidative/ER stress and cardiomyocyte apoptosis were up-modulated (p < 0.05), while SERCA2a, a key calcium handling channel, was downmodulated in the ISP group (p < 0.05). In contrast, HPA treatment ameliorated these ISP-induced myocardial aberrations. (p < 0.05).Conclusion: These results indicate that HPA might be a potential therapeutic candidate for MI and associated cardiac problems. Keywords: Caspase-12, ER stress, Huperzine A, Myocardial infarction, SERCA2a

scholarly journals 5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction

2021 ◽  
Vol 22 (21) ◽  
pp. 11405
Author(s):  
Takaaki Hashimoto ◽  
Takaaki Sugihara ◽  
Tsutomu Kanda ◽  
Tomoaki Takata ◽  
Hajime Isomoto
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Heme Oxygenase ◽  
Caspase 3 ◽  
Aminolevulinic Acid ◽  
Therapeutic Potential ◽  
B Cell Lymphoma ◽  
Heme Oxygenase 1 ◽  
Glucose Regulated Protein

Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to explore the therapeutic potential of 5-ALA on palmitate-induced ER stress and lipoapoptosis. Huh-7 cells were treated with palmitic acid (PA) (800 μM) to induce steatosis for eight hours. Steatosis was evaluated by Lipi-green staining. 5-ALA (200 μM) was added with PA. The gene expression levels of the nuclear factor erythroid 2–related factor 2 (NRF2), HO-1, Glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), C/EBP homologous protein (CHOP), and B-cell lymphoma 2 (BCL-2) were evaluated by RT-PCR. Caspase-3/7 activity was evaluated by fluorescein active Caspase-3/7 staining. Cell death was evaluated by Annexin V/SYTOX green staining. PA significantly induced steatosis and increased GRP78 expression in Huh-7 cells. 5-ALA significantly induced HO-1 and decreased GRP78 expression. ATF6 was subsequently decreased. However, NRF2 and CHOP expression were not altered. Anti-apoptotic BCL-2 expression significantly increased, and Caspase 3/7 activity and cell death also decreased. 5-ALA has a therapeutic potential on hepatic steatosis by suppressing ER stress and lipoapoptosis by attenuating GRP78 via HO-1 induction.

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