Glucagon-like peptide-1 attenuates endoplasmic reticulum stress–induced apoptosis in H9c2 cardiomyocytes during hypoxia/reoxygenation through the GLP-1R/PI3K/Akt pathways

Guan, Gaopeng; Zhang, Jun; Liu, Shengyuan; Huang, Wenyin; Gong, Ying; Gu, Xiang

doi:10.1007/s00210-019-01625-2

Cited by 20 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A decreased GLP1R (Figure 4F) expression under miR-1-3p mimics was observed. Researches have confirmed that GLP1R mediates ER stress reduction through GLP1R/PI3K/Akt pathway, which also involves ATF4/CHOP and Gadd34 (growth arrest and DNA damage-inducible protein), contributes to dephosphorylation of eIF2α (eukaryote initiation factor 2 α) [43,44].…”

Section: Discussionmentioning

confidence: 99%

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1

Gao

Liú

et al. 2021

Clinical Science

View full text Add to dashboard Cite

Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell inflammatory response, oxidative stress and apoptosis, causing serious pulmonary vascular leakage and interstitial edema. The current study investigated the effect of exosomal miRNAs on endothelial cells during sepsis. We found a significant increase in miR-1-3p expression in cecal ligation and puncture (CLP) rats exosomes sequencing and sepsis patients’ exosomes, and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro. However, the specific biological function of miR-1-3p in ALI remains unknown. Therefore, mimics or inhibitors of miR-1-3p were transfected to modulate its expression in HUVECs. Cell proliferation, apoptosis, contraction, permeability, and membrane injury were examined via cell counting kit-8 (CCK-8), flow cytometry, phalloidin staining, Transwell assay, lactate dehydrogenase (LDH) activity, and Western blotting. The miR-1-3p target gene was predicted with miRNA-related databases and validated by luciferase reporter. Target gene expression was blocked by siRNA to explore the underlying mechanisms. The results illustrated increased miR-1-3p and decreased stress-associated endoplasmic reticulum protein 1 (SERP1) expression both in vivo and in vitro. SERP1 was a direct target gene of miR-1-3p. Up-regulated miR-1-3p inhibits cell proliferation, promotes apoptosis and cytoskeleton contraction, increases monolayer endothelial cell permeability and membrane injury by targeting SERP1, which leads to dysfunction of endothelial cells and weakens vascular barrier function involved in the development of ALI. MiR-1-3p and SERP1 may be promising therapeutic candidates for sepsis-induced lung injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1

Gao

Liú

et al. 2021

Clinical Science

View full text Add to dashboard Cite

show abstract

“…Yang et al ( 42 ) have observed that the expression levels of CHOP and Grp78 are significantly upregulated in cardiomyocytes following I/R. During the H/R process, high CHOP and Grp78 expression levels in H9C2 cells are present ( 43 ). CHOP serves a role in the apoptosis signaling pathways ( 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of dexmedetomidine on hypoxia/reoxygenation injury in cardiomyocytes by regulating the CHOP signaling pathway

Shi

Liu

2020

Mol Med Rep

View full text Add to dashboard Cite

Hypoxia/reoxygenation (H/r) injury in myocardial cells occurs frequently during cardiac surgery and affects the prognosis of patients. The present study aimed to investigate the protective effects of dexmedetomidine (dex) on H/r injury and its association with the c/eBP-homologous protein (cHoP) signaling pathway. an H/r model was constructed in H9c2 cells to investigate the effects of dex on H/r injury. cell viability, apoptosis and lactate dehydrogenase (LDH) levels were determined by MTT, flow cytometry and 2,4-dinitrophenylhydrazine colorimetric assays, respectively. The expression levels of inflammatory factors were measured by reverse transcription-quantitative Pcr (rT-qPcr), and cHoP and glucose-regulated protein-78 (Grp78) expression levels were detected by rT-qPcr and western blotting. cHoP was overexpressed or knocked down to detect the cell viability, apoptosis, LDH level and the expression levels of inflammatory factors and Grp78. The results demonstrated that in the H/r group, cell viability was lower and apoptosis was higher, and that higher levels of LDH and inflammatory factors were present compared with those in the dex+H/r group. Silencing of CHOP significantly reversed the H/R-reduced cell viability, high apoptotic rate and ldH levels, as well as the elevated expression levels of inflammatory factors and Grp78 caused by H/r injury, whereas the overexpression of cHoP inhibited cell viability and promoted apoptosis, elevated ldH level and expression of inflammatory factors and Grp78 compared with the negative control. additionally, pretreatment with Dex significantly alleviated the H/R injury; thus, Dex may protect H9c2 cells against H/r induced cell injury, possibly by suppressing the cHoP signaling pathway.

show abstract

“…Under physiological conditions, CHOP is expressed at low levels; once activated by ERS, its expression level significantly increases, and this is considered to be an important marker of ERS [ 31 ]. Intracellular apoptotic signaling usually activates the mitochondrial pathway, facilitating the release of mitochondrial proapoptotic proteins and apoptosis-inducing factors and ultimately activating the caspase cascade and promoting apoptosis [ 32 ]. The present study revealed that the expression of ERS marker proteins GRP78 and CHOP in the I/R group and the DM + I/R group were markedly upregulated, demonstrating that ERS is involved in the occurrence of myocardial I/R-induced ALI, but showed no obvious differences between these groups in the current experimental background, and there seems to be no significant difference between these groups, which does not mean that no differences in injury occurred between the two groups.…”

Section: Discussionmentioning

confidence: 99%

The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic Rats

Huang

Long

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Oxymatrine (OMT) is the primary pharmacological component of Sophora flavescens Aiton., which has been shown to possess potent antifibrotic, antioxidant, and anti-inflammatory activities. The aim of the present study was to clarify the protective mechanism of OMT on acute lung injury (ALI) subjected to myocardial ischemia/reperfusion (I/R). Methods. A myocardial I/R-induced ALI model was achieved in diabetic rats by occluding the left anterior descending coronary artery for 1 h, followed by reperfusion for 1 h. The levels of inflammatory factors (tumor necrosis factor-α, interleukin- (IL-) 6, and IL-17) in bronchoalveolar lavage fluid were assessed using commercially available kits. The index of myocardial injury, including the detection of cardiac troponin I (cTnI), cardiac troponin T (cTnT), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB), was also determined using commercially available kits. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to identify histological changes. The expression levels of endoplasmic reticulum chaperone BiP (GRP78), DNA damage-inducible transcript 3 protein (CHOP), eukaryotic translation initiation factor 2-alpha kinase 3 (PERK), inositol dependent enzyme 1α (IRE1α), ATF6, caspase-3, -9, and-12, Bcl-2, and Bax were determined by Western blotting. The mRNA expression levels of GRP78 and CHOP were detected by reverse transcription-quantitative PCR. Results. Myocardial I/R increased the levels of cTnI, cTnT, LDH, and CK-MB in diabetic rats. Damaged and irregularly arranged myocardial cells were also observed, as well as more serious ALI with higher lung injury scores and WET/DRY ratios and lower PaO2. Moreover, the expression of key proteins of endoplasmic reticulum stress (ERS) was increased by I/R injury, including phosphorylated- (p-) PERK, p-IRE1ɑ, and ATF6, as well as decreased levels of apoptosis. These effects were all significantly reversed by OMT treatment. Conclusions. OMT protects against ALI subjected to myocardial I/R by inhibiting ERS in diabetic rats.

show abstract

Glucagon-like peptide-1 attenuates endoplasmic reticulum stress–induced apoptosis in H9c2 cardiomyocytes during hypoxia/reoxygenation through the GLP-1R/PI3K/Akt pathways

Cited by 20 publications

References 35 publications

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1

Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1

Protective effects of dexmedetomidine on hypoxia/reoxygenation injury in cardiomyocytes by regulating the CHOP signaling pathway

The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic Rats

Contact Info

Product

Resources

About