Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes

Du, Yuyang; Wang, Min; Liu, Xuesong; Zhang, Jingyi; Xu, Xudong; Xu, Huibi; Sun, Guibo; Sun, Xiaobo

doi:10.3389/fphar.2018.00180

Cited by 25 publications

(21 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The present study investigated the effects of H/R on the viability, damage and apoptosis of H9c2 cells. Consistent with a previous study (15), the data revealed that H/R decreased cell viability, increased cell damage and induced cell apoptosis in a time-dependent manner. Cell viability was reduced by ~40% following a 12/6 h hypoxia/reperfusion period.…”

Section: Discussionsupporting

confidence: 91%

“…The UPR is a defense mechanism directed toward cellular adaptation to alleviate the unfolded protein load; however, prolonged stress is associated with the activation of proapoptotic proteins, such as CHOP (19). A previous study reported that ER stress is increased following H/R treatment (15). Consistent with this study, the present findings indicated that GRP78, ATF6 and CHOP were upregulated in a time-dependent manner following H/R injury.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation‑induced injury of H9c2 cardiomyocytes

et al. 2019

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress and autophagy are involved in myocardial ischemia-reperfusion (I/R) injury; however, their roles in this type of injury remain unclear. The present study investigated the roles of ER stress and autophagy, and their underlying mechanisms, in H9c2 cells during hypoxia/reoxygenation (H/R) injury. Cell viability was detected by CCK-8 assay. The autophagy flux was monitored with mCherry-GFP-LC3-adenovirus transfection. The expression levels of autophagy-related proteins and ER stress-related proteins were measured by western blotting. Apoptosis was detected by flow cytometry and western blotting. The results indicated that autophagy was induced, ER stress was activated and apoptosis was promoted in H9c2 cells during H/R injury. The inhibition of ER stress by 4-phenylbutyrate or C/EBP homologous protein (CHOP)-targeting small interfering RNA (siRNA) decreased autophagy and ameliorated cell apoptosis during H/R injury. Activation of autophagy by rapamycin attenuated ER stress and ameliorated cell apoptosis. Inhibition of autophagy by 3-methyladenine or Beclin1-targeting siRNA aggravated ER stress and exacerbated cell apoptosis, and activation of ER stress by thapsigargin decreased autophagy and induced cell apoptosis. Collectively, the findings of the present study demonstrated that H/R induced apoptosis and autophagy via ER stress in H9c2 cells, and that CHOP may serve an important role in ER stress-induced autophagy and apoptosis. Autophagy, as an adaptive response, was activated by ER stress and alleviated ER stress-induced cell apoptosis during H/R injury.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 98%

Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation‑induced injury of H9c2 cardiomyocytes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Our group and several others have reported that TASAES exerts therapeutic effects on myocardial damage [34,35] and atherosclerosis [22,23]. AsC, isolated from TASAES, was also reported to have powerful cardioprotective effects against ischemia-reperfusion injury in our previous study [20,21]. Moreover, we demonstrated that another AsC analogue can protect against ox-LDL-damaged endothelial cell injury via autophagy induction [36], which prompted us to explore whether AsC has antiatherosclerotic effects and determine its protective mechanism.…”

Section: Discussionmentioning

confidence: 79%

“…Seem, which has been widely used in traditional Chinese medicine [19]. Recently, our group reported that AsC alleviated hypoxia/reoxygenation-induced cardiomyocyte apoptosis in vitro [20] and ex vivo [21] studies. Moreover, we found that total saponins of Aralia elata (Miq.)…”

Section: Introductionmentioning

confidence: 99%

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Luo

Gao

et al. 2020

Aging

Self Cite

View full text Add to dashboard Cite

Atherosclerosis-related cardiovascular disease is still the predominant cause of death worldwide. Araloside C (AsC), a natural saponin, exerts extensive anti-inflammatory properties. In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/-mouse model and RAW264.7 macrophages exposed to ox-LDL, AsC was evaluated for its effects on polarization and autophagy. AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in ox-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methyladenine and BECN1 siRNA obviously abolished the antiatherosclerotic and M2 macrophage polarization effects of AsC. Mechanistically, AsC targeted Sirt1and increased its expression, and this increase in expression was associated with increased autophagy and M2 phenotype polarization. In contrast, the effects of AsC were markedly blocked by EX527 and Sirt1 siRNA. Altogether, AsC attenuates foam cell formation and lessens atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy.

show abstract

“…The molecular chaperone heat shock protein 90 (HSP90) is highly abundant in stress responses (21) and is important for the stability and function of key regulatory kinases such as IRE1 and PERK (7,20,23). PERK interacts with HSP90 via its .…”

Section: Introductionmentioning

confidence: 99%

The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH

Zhang

Wang²,

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1–34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG’44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.

show abstract

Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes

Cited by 25 publications

References 54 publications

Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation‑induced injury of H9c2 cardiomyocytes

Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation‑induced injury of H9c2 cardiomyocytes

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH

Contact Info

Product

Resources

About