scholarly journals Endoplasmic reticulum stress occurs in association with the extrusion of toxic extracellular vesicles from human placentae treated with antiphospholipid antibodies

2020 ◽  
Vol 134 (5) ◽  
pp. 459-472 ◽  
Author(s):  
Yunhui Tang ◽  
Yan Chen ◽  
Yohanes Nursalim ◽  
Katie Groom ◽  
Anthony Hickey ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Cell Activation ◽  
Misfolded Proteins ◽  
Caspase 8 ◽  
Hsp 70 ◽  
Maternal Risk ◽  
Tnf Α

Abstract Antiphospholipid autoantibodies (aPLs), a major maternal risk factor for preeclampsia, are taken into the syncytiotrophoblast where they bind intracellular vesicles and mitochondria. Subsequently, large quantities of extracellular vesicles (EVs) extruded from syncytiotrophoblast into the maternal circulation are altered such that they cause maternal endothelial cell activation. However, the mechanism driving this change is unknown. First trimester placental explants were treated with aPL for 18 h. The EVs were then collected by different centrifugation. The levels of HSP 70, misfolded proteins, caspase 8 activity, and Mixed Lineage Kinase domain-Like (MLKL) were measured in placental explants and EVs. In addition, the levels of TNF-α and CD95 in conditioned medium were also measured. Treating placental explants with aPL caused an increase in levels of HSP 70, misfolded proteins and MLKL in placental explants and EVs. Increased activity of caspase 8 was also seen in placental explants. Higher levels of TNF-α were seen conditioned medium from aPL-treated placental explant cultures. aPLs appear to induce endoplasmic reticulum stress in the syncytiotrophoblast in a manner that involved caspase 8 and TNF-α. To avoid accumulation of the associated misfolded proteins and MLKL, the syncytiotrophoblast exports these potentially dangerous proteins in EVs. It is likely that the dangerous proteins that are loaded into placental EVs in preeclampsia contribute to dysfunction of the maternal cells.

scholarly journals Modulation of Endoplasmic Reticulum Stress Controls CD4+ T-cell Activation and Antitumor Function

2017 ◽  
Vol 5 (8) ◽  
pp. 666-675 ◽  
Author(s):  
Jessica E. Thaxton ◽  
Caroline Wallace ◽  
Brian Riesenberg ◽  
Yongliang Zhang ◽  
Chrystal M. Paulos ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
T Cell ◽  
Endoplasmic Reticulum Stress ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell

Interaction between caspase-8 activation and endoplasmic reticulum stress in glycochenodeoxycholic acid-induced apoptotic HepG2 cells

Toxicology ◽  
2007 ◽  
Vol 241 (3) ◽  
pp. 146-156 ◽  
Author(s):  
Toru Iizaka ◽  
Mayumi Tsuji ◽  
Hideto Oyamada ◽  
Yuri Morio ◽  
Katsuji Oguchi
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Hepg2 Cells ◽  
Caspase 8

scholarly journals Excessive training is associated with endoplasmic reticulum stress but not apoptosis in the hypothalamus of mice

2017 ◽  
Vol 42 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Ana Paula Pinto ◽  
Alisson Luiz da Rocha ◽  
Bruno Cesar Pereira ◽  
Luciana da Costa Oliveira ◽  
Gustavo Paroschi Morais ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Downhill Running ◽  
Stress Markers ◽  
Caspase 12 ◽  
Tnf Α

Downhill running-based overtraining model increases the hypothalamic levels of IL-1β, TNF-α, SOCS3, and pSAPK-JNK. The aim of the present study was to verify the effects of 3 overtraining protocols on the levels of BiP, pIRE-1 (Ser724), pPERK (Thr981), pelF2α (Ser52), ATF-6, GRP-94, caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) proteins in the mouse hypothalamus. The mice were randomized into the control, overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. After the overtraining protocols (i.e., at the end of week 8), hypothalamus was removed and used for immunoblotting. The OTR/down group exhibited increased levels of all of the analyzed endoplasmic reticulum stress markers in the hypothalamus at the end of week 8. The OTR/up and OTR groups exhibited increased levels of BiP, pIRE-1 (Ser724), and pPERK (Thr981) in the hypothalamus at the end of week 8. There were no significant differences in the levels of caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) between the experimental groups at the end of week 8. In conclusion, the 3 overtraining protocols increased the endoplasmic reticulum stress at the end of week 8.

scholarly journals Endoplasmic Reticulum Stress Contributes to Nociception via Neuroinflammation in a Murine Bone Cancer Pain Model

2020 ◽  
Vol 132 (2) ◽  
pp. 357-372 ◽  
Author(s):  
Yanting Mao ◽  
Chenchen Wang ◽  
Xinyu Tian ◽  
Yulin Huang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Pain ◽  
Inflammatory Mediators ◽  
Bone Cancer ◽  
Intrathecal Administration ◽  
Bone Cancer Pain ◽  
Stress Markers ◽  
Mechanical Threshold ◽  
Tnf Α

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development. Methods The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed. Results Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P < 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment. Conclusions Inhibition of inflammatory mediator–triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.

scholarly journals Cutting Edge: Endoplasmic Reticulum Stress Licenses Macrophages To Produce Mature IL-1β in Response to TLR4 Stimulation through a Caspase-8– and TRIF-Dependent Pathway

2014 ◽  
Vol 192 (5) ◽  
pp. 2029-2033 ◽  
Author(s):  
Kevin Shenderov ◽  
Nicolas Riteau ◽  
Ronald Yip ◽  
Katrin D. Mayer-Barber ◽  
Sandy Oland ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cutting Edge ◽  
Caspase 8 ◽  
Dependent Pathway

TNF-α transiently induces endoplasmic reticulum stress and an incomplete unfolded protein response in the hypothalamus

Neuroscience ◽  
2010 ◽  
Vol 170 (4) ◽  
pp. 1035-1044 ◽  
Author(s):  
R.G. Denis ◽  
A.P. Arruda ◽  
T. Romanatto ◽  
M. Milanski ◽  
A. Coope ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Tnf Α ◽  
Protein Response
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