scholarly journals Neuroprotective Effects of Exercise Postconditioning After Stroke via SIRT1-Mediated Suppression of Endoplasmic Reticulum (ER) Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Fengwu Li ◽  
Xiaokun Geng ◽  
Hangil Lee ◽  
Melissa Wills ◽  
Yuchuan Ding
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Ros Production ◽  
Post Stroke ◽  
Caspase 12 ◽  
Stress Pathway

While it is well-known that pre-stroke exercise conditioning reduces the incidence of stroke and the development of comorbidities, it is unclear whether post-stroke exercise conditioning is also neuroprotective. The present study investigated whether exercise postconditioning (PostE) induced neuroprotection and elucidated the involvement of SIRT1 regulation on the ROS/ER stress pathway. Adult rats were subjected to middle cerebral artery occlusion (MCAO) followed by either: (1) resting; (2) mild exercise postconditioning (MPostE); or (3) intense exercise postconditioning (IPostE). PostE was initiated 24 h after reperfusion and performed on a treadmill. At 1 and 3 days thereafter, we determined infarct volumes, neurological defects, brain edema, apoptotic cell death through measuring pro- (BAX and Caspase-3) and anti-apoptotic (Bcl-2) proteins, and ER stress through the measurement of glucose-regulated protein 78 (GRP78), inositol-requiring 1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), Caspase-12, and SIRT1. Proteins were measured by Western blot. ROS production was detected by flow cytometry.Compared to resting rats, both MPostE and IPostE significantly decreased brain infarct volumes and edema, neurological deficits, ROS production, and apoptotic cell death. MPostE further increased Bcl-2 expression and Bcl-2/BAX ratio as well as BAX and Caspase-3 expressions and ROS production (*p < 0.05). Both PostE groups saw decreases in ER stress proteins, while MPostE demonstrated a further reduction in GRP78 (***p < 0.001) and Caspase-12 (*p < 0.05) expressions at 1 day and IRE1α (**p < 0.01) and CHOP (*p < 0.05) expressions at 3 days. Additionally, both PostE groups saw significant increases in SIRT1 expression.In this study, both mild and intense PostE levels induced neuroprotection after stroke through SIRT1 and ROS/ER stress pathway. Additionally, the results may provide a base for our future study regarding the regulation of SIRT1 on the ROS/ER stress pathway in the biochemical processes underlying post-stroke neuroprotection. The results suggest that mild exercise postconditioning might play a similar neuroprotective role as intensive exercise and could be an effective exercise strategy as well.

scholarly journals Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Prachya Janhom ◽  
Permphan Dharmasaroja
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Caspase 3 ◽  
Nuclear Dna ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Concomitant Treatment ◽  
Ros Production ◽  
Cellular Models ◽  
Induced Apoptosis

In vitrostudies have shown that extracts from mangosteen (Garcinia mangostanaLinn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson’s disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.

scholarly journals Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Marianna Holczer ◽  
Boglárka Besze ◽  
Veronika Zámbó ◽  
Miklós Csala ◽  
Gábor Bánhegyi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Egcg Treatment ◽  
Life And Death ◽  
Er Stress Response ◽  
Negative Effect ◽  
External Stimuli

The maintenance of cellular homeostasis is largely dependent on the ability of cells to give an adequate response to various internal and external stimuli. We have recently proposed that the life-and-death decision in endoplasmic reticulum (ER) stress response is defined by a crosstalk between autophagy, apoptosis, and mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival to apoptotic cell death is controlled by GADD34. The aim of the present study was to investigate the role of epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, in promoting autophagy-dependent survival and to verify the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER stress. Our findings, obtained by using HEK293T cells, revealed that EGCG treatment is able to extend cell viability by inducing autophagy. We confirmed that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore, it also required ULK1. We show that pretreatment of cells with EGCG diminishes the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment) on autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy-dependent survival even in the absence of GADD34. Our data suggest a novel role for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK pathways in ER stress.

scholarly journals Acidosis Causes Endoplasmic Reticulum Stress and Caspase-12-Mediated Astrocyte Death

2005 ◽  
Vol 25 (3) ◽  
pp. 358-370 ◽  
Author(s):  
Koji Aoyama ◽  
David M Burns ◽  
Sang Won Suh ◽  
Philippe Garnier ◽  
Yasuhiko Matsumori ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Active Form ◽  
Protein Synthesis Inhibitor ◽  
Nuclear Condensation ◽  
Caspase 12 ◽  
Delayed Cell Death

Endoplasmic reticulum (ER) stress leads to activation of caspase-12, which in turn can lead to activation of caspase-3 and cell death. Here we report that transient acidosis induces ER stress and caspase-12-mediated cell death in mouse astrocytes. After a 3-hour incubation at pH 6.0, astrocytes exhibited delayed cell death associated with nuclear condensation and fragmentation. Cell death was reduced by the protein synthesis inhibitor cycloheximide, further suggesting an active cell death program. Acidosis increased the expression of the ER chaperone protein GRP-78, indicative of ER stress. Acidosis also increased caspase-12 mRNA expression, caspase-12 protein expression, cleavage of caspase-12 to its active form, and activation of caspase-3. Each of these effects was suppressed in astrocytes pretreated with caspase-12 antisense phosphorodiamidate morpholino oligodeoxynucleotides (PMOs). Caspase-12 antisense PMOs also reduced the cell death induced by acidosis. Immunoprecipitation studies showed dissociation of both caspase-12 and Ire1-α from GRP-78, thereby suggesting a mechanism by which acidosis can initiate the ER stress response. To evaluate caspase-12 activation in vivo, rats were subjected to middle cerebral artery ischemia–reperfusion. Immunostaining of brain sections harvested 24 hours later showed increased caspase-12 expression and nuclear condensation in astrocytes of the periinfarct region exposed to acidosis during ischemia. These findings suggest that acidosis induces ER stress and caspase-12 activation, and that these changes may contribute to delayed cell death after ischemia.

scholarly journals GanDouLing combined with Penicillamine improves cerebrovascular injury via PERK/eIF2α/CHOP endoplasmic reticulum stress pathway in the mouse model of Wilson’s disease

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yonghua Chen ◽  
Bo Zhang ◽  
Shijian Cao ◽  
Wei Huang ◽  
Ni Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mouse Model ◽  
Er Stress ◽  
Vascular Injury ◽  
Caspase 3 ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Cerebrovascular Injury ◽  
Caspase 12 ◽  
Stress Pathway

We aim to investigate the function and mechanism of GanDouLing combinated with Penicillamine on cerebrovascular injury in Wilson’s disease (WD). ELISA was performed to analyze the expression of vascular injury factors. Pathological changes of cerebral vessels were observed by HE stain. Immunohistochemistry assays were performed to analyze the expression of ICAM-1, VCAM-1, and GRP78. Western blotting was measured to analyze the expression of caspase-3, caspase-12, PERK, eIF2α, and CHOP. Apoptosis was detected with TUNEL assay. The expression of vascular injury factors and ICAM-1, VCAM-1 was significantly increased by WD and markedly decreased in GanDouLing-Penicillamine group. The expression of caspase-3, caspase-12, PERK, eIF2α, and CHOP were obviously expressed in Wilson group, GanDouLing-Penicillamine suppressed apoptosis and endoplasmic reticulum (ER) stress. Our findings suggested that GanDouLing-Penicillamine improved cerebrovascular injury through PERK/eIF2α/CHOP ER stress pathway in the mouse model of WD.

scholarly journals 3 β-Hydroxysteroid-Δ 24 Reductase (DHCR24) Protects Neuronal Cells from Apoptotic Cell Death Induced by Endoplasmic Reticulum (ER) Stress

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86753 ◽  
Author(s):  
Xiuli Lu ◽  
Yang Li ◽  
Weiqi Wang ◽  
Shuchao Chen ◽  
Ting Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Neuronal Cells ◽  
Apoptotic Cell Death

scholarly journals The long noncoding RNA of RMRP is downregulated by PERK, which induces apoptosis in hepatocellular carcinoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Yukimoto ◽  
Takao Watanabe ◽  
Kotaro Sunago ◽  
Yoshiko Nakamura ◽  
Takaaki Tanaka ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Transcriptome Analysis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Chronic Liver ◽  
Mitochondrial Rna

AbstractEndoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.

scholarly journals Endoplasmic Reticulum Stress Contributed to Dipyridamole-Induced Impaired Autophagic Flux and Glioma Apoptosis

2022 ◽  
Vol 23 (2) ◽  
pp. 579
Author(s):  
Cheng-Yi Chang ◽  
Chih-Cheng Wu ◽  
Jiaan-Der Wang ◽  
Su-Lan Liao ◽  
Wen-Ying Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Glioma Cells ◽  
Apoptotic Cell Death ◽  
Autophagic Flux ◽  
Intracellular Camp ◽  
Cell Proliferation Inhibition ◽  
Camp Levels

Elevation of intracellular cAMP levels has been implicated in glioma cell proliferation inhibition, differentiation, and apoptosis. Inhibition of phosphodiesterase is a way to elevate intracellular cAMP levels. The present study aimed to investigate the anti-glioma potential of dipyridamole, an inhibitor of phosphodiesterase. Upon treatment with dipyridamole, human U87 glioma cells decreased cell viability, clonogenic colonization, migration, and invasion, along with Noxa upregulation, Endoplasmic Reticulum (ER) stress, impaired autophagic flux, Yes-associated Protein 1 (YAP1) phosphorylation, and YAP1 reduction. Pharmacological and genetic studies revealed the ability of dipyridamole to initiate Noxa-guided apoptosis through ER stress. Additionally, the current study further identified the biochemical role of YAP1 in communicating with ER stress and autophagy under situations of dipyridamole treatment. YAP1 promoted autophagy and protected glioma cells from dipyridamole-induced apoptotic cell death. Dipyridamole impaired autophagic flux and rendered glioma cells more vulnerable to apoptotic cell death through ER stress-inhibitable YAP1/autophagy axis. The overall cellular changes caused by dipyridamole appeared to ensure a successful completion of apoptosis. Dipyridamole also duplicated the biochemical changes and apoptosis in glioma T98G cells. Since dipyridamole has additional biochemical and pharmacological properties, further research centered on the anti-glioma mechanisms of dipyridamole is still needed.

scholarly journals Saturated fatty acids induce endoplasmic reticulum stress in primary cardiomyocytes

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Taha Haffar ◽  
Félix-Antoine Bérubé-Simard ◽  
Jean-Claude Tardif ◽  
Nicolas Bousette
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Apoptotic Cell ◽  
Saturated Fatty Acids ◽  
Fatty Acid Uptake ◽  
Apoptotic Cell Death ◽  
Acid Uptake

AbstractAbstract: Introduction: Diabetes is a major contributor to cardiovascular disease. There is a growing body of evidence pointing towards intra-myocellular lipid accumulation as an integral etiological factor. Here we aimed to determine the effect of two common fatty acids on lipid accumulation and cellular stress in primary cardiomyocytes.Methods: We evaluated lipid accumulation biochemically (by triacylglyceride assay and radiolabeled fatty acid uptake assay) as well as histologically (by BODIPY 493/503 staining) in mouse and rat neonatal cardiomyocytes treated with saturated (palmitate) or mono-unsaturated (oleate) fatty acids. Endoplasmic reticulum (ER) stress was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability was assessed by propidium iodide staining.Results: We found that both oleate and palmitate led to significant increases in intracellular lipid in cardiomyocytes; however there were distinct differences in the qualitative nature of BODIPY staining between oleate and palmitate treated cardiomyocytes. We also show that palmitate caused significant apoptotic cell death and this was associated with ER stress. Interestingly, co-administration of oleate with palmitate abolished cell death, and ER stress. Finally, palmitate treatment caused a significant increase in ubiquitination of Grp78, a key compensatory ER chaperone.Conclusion: Palmitate causes ER stress and apoptotic cell death in primary cardiomyocytes and this is associated with apparent differences in BODIPY staining compared to oleate treated cardiomyocytes. Importantly, the lipotoxic effects of palmitate are abolished with the co-administration of oleate.

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