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Transcription Factor CHOP

About: Transcription Factor CHOP is a research topic. Over the lifetime, 443 publications have been published within this topic receiving 46408 citations.


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Journal ArticleDOI
TL;DR: It is demonstrated that elevated concentrations of UCB (50 μM) are able to activate select components of the ER stress pathway in Hepa 1c1c7 cells, which may contribute to UCB‐mediated apoptosis.
Abstract: Elevated concentrations of unconjugated bilirubin (UCB) are responsible for neonatal jaundice and can eventually lead to kernicterus or death. The molecular mechanism of UCB toxicity is incompletely elucidated. The purpose of this study was to analyze changes in gene regulation mediated by UCB to determine novel pathways that contribute to UCB-mediated toxicity. We employed microarray analysis to determine changes in gene regulation mediated by UCB at both pro- (50 μM) and antioxidant (70 nM) concentrations in Hepa 1c1c7 cells at 1 and 6 h. The changes observed in select genes were validated with qPCR. Using immunoblot analysis, we validated these changes at the protein level for select genes and documented the activation of two proteins involved in the endoplasmic reticulum (ER) stress pathway, eIF2α and PERK. Following treatment with 50 μM UCB, microarray analysis revealed the upregulation of many genes involved in ER stress (ATF3, BiP, CHOP, Dnajb1, and Herp). We demonstrate that upregulation of the proapoptotic transcription factor CHOP results in increased intracellular protein content. It was determined that activation of proteins involved in ER stress was an early event in UCB toxicity as eIF2α and PERK were both phosphorylated and activated by 1 h posttreatment. We also demonstrate that procaspase-12 content, a proposed initiator caspase in ER stress-mediated apoptosis, is decreased by 4 h posttreatment. In conclusion, this study demonstrates that elevated concentrations of UCB (50 μM) are able to activate select components of the ER stress pathway in Hepa 1c1c7 cells, which may contribute to UCB-mediated apoptosis. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:73–88, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20313

13 citations

Journal ArticleDOI
TL;DR: It is suggested that reduction of ABCG1 induces endothelial apoptosis, which seems associated with intracellular free cholesterol accumulation and subsequent ER stress.
Abstract: The present study was focused on whether ABCG1 deficiency was involved in endothelial apoptosis and its possible mechanism. Human umbilical artery endothelial cells were transfected with ABCG1 siRNA and/or ABCG1 expression plasmid. We observed that silencing of endothelial ABCG1 reduced cholesterol efflux to HDL and increased intracellular lipid content. Moreover, reduction of ABCG1 promoted endothelial apoptosis and expression of endoplasmic reticulum (ER) stress-related molecules GRP78 and CHOP. In contrast, transfection of ABCG1 overexpression plasmid reversed endothelial apoptosis and intracellular lipid accumulation as well as decreased expression of GRP78 and CHOP in ABCG1-deficient endothelial cells. Furthermore, endothelial apoptosis and ER stress-related molecules were induced by repletion of endothelial cells with cholesterol-loaded cyclodextrin, otherwise endothelial apoptotic response and expression of GRP78 and CHOP were suppressed by depletion of cellular cholesterol in ABCG1-deficient endothelial cells. The present results suggest that reduction of ABCG1 induces endothelial apoptosis, which seems associated with intracellular free cholesterol accumulation and subsequent ER stress.

13 citations

Journal ArticleDOI
TL;DR: It is demonstrated that ER stress induced by BMAA is the important mediator of neuronal injury and apoptotic death, and suggests development in novel therapeutic strategies for treatment.
Abstract: β-N-methylamino-L-alanine (BMAA) is a neurotoxin that is closely associated with the incidence of amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. In cultured neuronal cells, BMAA notably induces the upregulation of endoplasmic reticulum (ER) chaperons and activates the unfolded protein response (UPR) receptor pathways of protein kinase RNA‑like endoplasmic reticulum kinase, inositol‑requiring kinase 1 and transcription factor 6. The ER stress‑specific protein CCAAT/‑enhancer‑binding protein homologous protein (CHOP) affords pro‑apoptotic responses that cause mitochondrial damage and caspase activation. BMAA also induces the activation of mitogen‑activated protein kinase member c‑JUN N‑terminal kinase, p38 and extracellular signal‑regulated kinase, which have been suggested to be involved in the signaling pathway of UPR‑mediated apoptosis. Inhibition of ER stress using ER stress antagonist, salubrinal, attenuated the expression of CHOP and alleviated neuronal death. Overexpression of heat shock protein 70 suppressed the activation of UPR receptors and UPR‑evoked apoptotic signaling. The present findings demonstrated that ER stress induced by BMAA is the important mediator of neuronal injury and apoptotic death, and suggests development in novel therapeutic strategies for treatment.

13 citations

Journal ArticleDOI
TL;DR: The findings indicate that regulated expression of Chop during obesity is critical for adaptation to chronic caloric excess and maintenance of energy homeostasis via integration of metabolic and immune systems.

13 citations

Journal ArticleDOI
TL;DR: High-throughput screening is used to identify a series of 1,2,3-triazole amide derivatives that inhibit ER stress-induced CHOP-luciferase reporter activity and shows that compounds with an N,1-diphenyl-5-methyl-1H-1,2-3-Triazole-4-carboxamide backbone potently protect β cell against ER stress.

13 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20213
20203
20193
201811
201719
201648