IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder carcinoma T24 cells

Zeng, Tao; Peng, Lifen; Chao, Haichao; Xi, Haibo; Fu, Bin; Wang, Yibing; Zhu, Zunwei; Wang, Gongxian

doi:10.1016/j.bbrc.2015.03.064

Cited by 48 publications

(32 citation statements)

References 22 publications

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“…Activated ASK1 finally promotes apoptosis via a series of cascade reactions. 64,65 Recent studies have also proven that ERS is involved in the activation of NLRP3 inflammasomes 66 After activating the unfolded protein response (UPR), ERS can promote the transcription of thioredoxin interaction protein (TXNIP) by binding IRE1α and PERK, and inhibit TXNIP by modulating miRNA-17, thereby regulating TXNIP to induce ROS production and activate NLRP3 inflammasomes. [66][67][68] Above all, we verified that the ERS/ASK1/NLRP3 inflammasome pathway is involved in the ox-LDL-induced cholesterol efflux that occurs in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

Hang

Peng

Xiang

et al. 2020

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These authors contributed equally to this workObjective: This study was to investigate the mechanism of inflammatory pathology modification induced by ox-LDL in endothelial cells. Methodology: In this study, we firstly investigated the efflux of cholesterol of endothelial cells under the treatment of ox-LDL, and cell proliferation, ROS production, cell apoptosis was measured. Further, proteins of ASK1, NLRP3 inflammasomes and endoplasmic reticulum stress response were detected. Afterwards, ASK1 inhibitor (GS-4997) or endoplasmic reticulum stress (ERS) inhibitor (4-PBA) was used to measure the performance of endothelial cells. Results: In this study, endothelial cells were treated with ox-LDLs alone or in combination with a GS-4997 or 4-PBA. Results showed that ox-LDLs attenuated the efflux of cholesterol from endothelial cells in a dose-dependent manner. Ox-LDLs inhibited the proliferation of endothelial cells, and induced their apoptosis and production of reactive oxygen species (ROS). Additionally, ox-LDLs upregulated the levels of phosphorylated ASK1, ERS-related proteins (chop, p-PERK, GRP78, and p-IRE-1), and inflammation-associated proteins (NLRP3, IL-1β, and caspase 1) in endothelial cells. Moreover, we proved that GS-4997 could partly reverse ox-LDL-mediated cell proliferation, apoptosis, ROS production, and inflammation in endothelial cells, and increase cholesterol efflux. We also found that 4-PBA could attenuate the effects of ox-LDLs on endothelial cell cholesterol efflux, proliferation, apoptosis, ROS production, and inflammation. Conclusion: Our results suggest that cholesterol efflux from endothelial cells is reduced by ox-LDLs, and these reductions in cholesterol efflux are accompanied by increased NLRP3 inflammasome signaling, ASK1 and higher levels of endoplasmic reticulum stress. Our results suggest this axis as potential targets for treating atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

Hang

Peng

Xiang

et al. 2020

DDDT

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“…Then, we explored whether supernormal Ca 2+ signaling and elevated ER Ca 2+ store would be associated with the apoptosis of Tmco1 −/− GCs. As the most sensitive branch of UPR [ 37 ], IRE1α stimulates TRAF2 (tumor necrosis factor receptor associated factor 2), which then activates the ASK1 (apoptosis signal-regulating kinase 1) and forms IRE1α-TRAF2-ASK1 complex to phosphorylate and activate JNK [ 38 ]. We found IRE1α activation was higher and the level of BCL2 was reduced, while the levels of PUMA, BAX, cleaved caspase 9, and activated caspase 3 were increased in Tmco1 −/− GCs.…”

Section: Discussionmentioning

confidence: 99%

TMCO1 is essential for ovarian follicle development by regulating ER Ca2+ store of granulosa cells

et al. 2018

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TMCO1 (transmembrane and coiled-coil domains 1) is an endoplasmic reticulum (ER) transmembrane protein that actively prevents Ca2+ stores from overfilling. To characterize its physiological function(s), we generated Tmco1−/− knockout (KO) mice. In addition to the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, Tmco1−/− females manifest gradual loss of ovarian follicles, impaired ovarian follicle development, and subfertility with a phenotype analogous to the premature ovarian failure (POF) in women. In line with the role of TMCO1 as a Ca2+ load-activated Ca2+ channel, we have detected a supernormal Ca2+ signaling in Tmco1−/− granulosa cells (GCs). Interestingly, although spontaneous Ca2+ oscillation pattern was altered, ER Ca2+ stores of germinal vesicle (GV) stage oocytes and metaphase II (MII) arrested eggs were normal upon Tmco1 ablation. Combined with RNA-sequencing analysis, we also detected increased ER stress-mediated apoptosis and enhanced reactive oxygen species (ROS) level in Tmco1−/− GCs, indicating the dysfunctions of GCs upon TMCO1 deficiency. Taken together, these results reveal that TMCO1 is essential for ovarian follicle development and female fertility by maintaining ER Ca2+ homeostasis of GCs, disruption of which causes ER stress-mediated apoptosis and increased cellular ROS level in GCs and thus leads to impaired ovarian follicle development.

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“…These processes are identified as the unfolded protein response (UPR) [10,11] . However, if unresolved, ERS is lethal to cells via what is recognized as ERSinduced apoptosis [12] .…”

Section: Endoplasmic Reticulum Stress Suppresses Proteins Synthesis Amentioning

confidence: 99%

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

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Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.

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IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder carcinoma T24 cells

Cited by 48 publications

References 22 publications

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

TMCO1 is essential for ovarian follicle development by regulating ER Ca2+ store of granulosa cells

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

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