The unfolded protein response, inflammation, oscillators, and disease: a systems biology approach

Rangel-Aldao, Rafael

doi:10.1515/ersc-2015-0003

Cited by 4 publications

(5 citation statements)

References 170 publications

(228 reference statements)

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“…The subsequent experiments revealed that the expression levels of ERS-related genes, such as GRP78, IRE1, p50ATF6 and CHOP, were increased in cells treated with TM + H 2 O 2, compared with cells treated with H 2 O 2 alone. It is well known that in the absence of ERS, the N-terminus of IRE1, p50ATF6 and PERK binds to the chaperone Grp78/Bip and they are present in inactive state ( 6 , 11 ). When ERS occurs, a large number of unfolded proteins accumulate in the ER cavity, IRE1, p50ATF6 and PERK are then separated from Grp78/Bip, and Grp78/Bip binds to the unfolded proteins ( 11 , 14 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…When the ER homeostastic balance is disrupted by a variety of physiological and pathological factors, ER stress (ERS) can be induced in the ER with increased amounts of unfolded and misfolded proteins being formed, calcium depletion and disorder of lipid synthesis ( 5 , 6 ). ERS involves three pathways, namely the unfolded protein response (UPR), Ca 2+ signaling and ER-related degradation ( 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

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Roles of endoplasmic reticulum stress and autophagy on H2O2‑induced oxidative stress injury in HepG2 cells

Wang

Fang

et al. 2018

Mol Med Report

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Endoplasmic reticulum stress (ERS) can be induced by a variety of physiological and pathological factors including oxidative stress, which triggers the unfolded protein response to deal with ERS. Autophagy has been hypothesized to be a means for tumor cells to increase cell survival under conditions of hypoxia, metabolic stress and even chemotherapy. Although they may function independently from each other, there are also interactions between responses to oxidative stress injury induced by pathologic and pharmacological factors. The aim of the present study was to investigate the effects of ERS and autophagy on H2O2-induced oxidative stress injury in human HepG2 hepatoblastoma cells. It was demonstrated that exposure of HepG2 cells to H2O2 decreased cell viability and increased reactive oxygen species (ROS) levels in a dosage-dependent manner. In addition, apoptosis and autophagy rates were elevated and reduced following cell exposure to H2O2 + the ERS inducer Tunicamycin (TM), and to H2O2 + the ERS inhibitor Salubrinal (SAL), compared with the cells treated with H2O2 alone, respectively. Further studies revealed that TM enhanced the expression of ERS-related genes including glucose-regulated protein-78/binding immunoglobulin protein, inositol-requiring kinase-I and activating transcription factor 6 and C/EBP-homologous protein 10, which were attenuated by SAL compared with cells exposed to H2O2 alone. The data from the present study also demonstrated that LC3II/LC3-I and p62, members of autophagy-related genes, were increased and decreased in cells treated with H2O2 + TM compared with cells treated with H2O2, respectively, indicating that autophagy was stimulated by ERS. Furthermore, a reduction in the levels of pro caspase-3 and pro caspase-9, and elevation level of caspase-12 were observed in cells exposed to H2O2 + TM compared with cells treated with H2O2, respectively, suggesting apoptosis induced by H2O2 was enhanced by ERS or autophagy triggered by H2O2. The above results suggest that the ERS inducer may be a potential target for pharmacological intervention targeted to ERS or autophagy to enhance oxidative stress injury of tumor cells induced by antitumor drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of endoplasmic reticulum stress and autophagy on H2O2‑induced oxidative stress injury in HepG2 cells

Wang

Fang

et al. 2018

Mol Med Report

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“…The ER is an important organelle for protein synthesis, folding, and modification and for calcium storage and lipid synthesis [12]. Many physiological and pathological factors, including inflammation, hypoxia, glucose deficiency, environmental toxins, viral infection, changes in Ca 2+ levels, and oxidative stress, destroy the homeostasis of ER and lead to ER dysfunction [13,14]. Dysfunction in the ER can increase the production of the misfolded or unfolded proteins in ER that can induce ER stress and trigger the unfolded protein response (UPR) [15,16].…”

Section: Overview Of Endoplasmic Reticulum Stressmentioning

confidence: 99%

Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases

Zhao

Liu

Yang

et al. 2022

IJMS

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Endoplasmic reticulum (ER) plays important roles in protein synthesis, protein folding and modification, lipid biosynthesis, calcium storage, and detoxification. ER homeostasis is destroyed by physiological and pharmacological stressors, resulting in the accumulation of misfolded proteins, which causes ER stress. More and more studies have shown that ER stress contributes to the pathogenesis of many diseases, such as diabetes, inflammation, neurodegenerative diseases, cancer, and autoimmune diseases. As a toxic gas, H2S has, in recent years, been considered the third most important gas signal molecule after NO and CO. H2S has been found to have many important physiological functions and to play an important role in many pathological and physiological processes. Recent evidence shows that H2S improves the body’s defenses to many diseases, including diabetes, by regulating ER stress, but its mechanism has not yet been fully understood. We therefore reviewed recent studies of the role of H2S in improving diabetes-related diseases by regulating ER stress and carefully analyzed its mechanism in order to provide a theoretical reference for future research.

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“…The NLRP3 inflammasome is the most known inflammasome. It is a multiprotein citoplasmic complex activated by pathogen-associated molecular patterns (PAMPs) (such as bacterial and viral nucleic acid), damage-associated molecular patterns (DAMPs) (for example, ATP and uric acid crystals) or environmental irritans [1][2][3].…”

Section: Short Communicationmentioning

confidence: 99%

Colorectal Cancer and NLRP-Current Knowledge

J¹

2018

Immunome Res

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Inflammasomes activated by different stimuli in colorectal cancer show dual effect on cancer's destiny. Activation of caspase-1 results in maturation of IL-1β and IL-18. IL-1β suppresses NK and T cells activity against tumor, induces expression of metastatic genes and stimulates the production of proinflammatory leukines, but it also enhances NK cell-mediated death of colon carcinoma cells. IL-18 promoter polymorphisms in humans increase risk for colorectal cancers.One variant of NLRP3 gene in human is connected with increased susceptibility to colorectal cancer. Expression levels of NLRP1, NLRP3, NLRC4 were significantly reduced in human CRC compared with healthy controls. Nlrp3 −/−mice exhibited increased colorectal cancer and metastasis in liver.NLRP3 have an important role in the Epithelial-Mesenchymal Transition (EMT) of colorectal cancer cells, which is necessary for migration and invasion. Absence of NLRP3 in colorectal carcinoma cells diminishes tumor cells migration and invasion.

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The unfolded protein response, inflammation, oscillators, and disease: a systems biology approach

Cited by 4 publications

References 170 publications

Roles of endoplasmic reticulum stress and autophagy on H2O2‑induced oxidative stress injury in HepG2 cells

Roles of endoplasmic reticulum stress and autophagy on H2O2‑induced oxidative stress injury in HepG2 cells

Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases

Colorectal Cancer and NLRP-Current Knowledge

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