• Journal of Life Science
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• v.22 no.8
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• pp.1132-1136
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• 2012

Many kind of cell stresses induce gene expression of unfolded protein response (UPR)-associated factors. This study demonstrated that up- and down-regulation of gene expression of endoplasmic reticulum (ER) stress chaperones and ER stress sensors was induced by immobilization stress in the rat organs (adrenal gland, liver, lung, muscle). However, no statistically significant regulation was detected in the others (heart, spleen, thymus, kidney, testis). The results are the first to show that immobilization stress induces UPR associated gene expression, will help to explain immobilization stress-associated ER stress.

• Journal of Life Science
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• v.23 no.9
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• pp.1104-1108
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• 2013

Ethylene glycol (EG) is the most commonly used for automotive antifreeze, and it's easily misuseful for human. EG poisoning occurs in suicide attempts and infrequently, either intentionally through misuse or accidentally because of sweet taste. Though EG itself is mild toxic to the human body, it becomes higher toxic organic acids by in vivo broken down that are responsible for extensive cellular damage in various tissues caused principally by the metabolites. It is already well known that various cellular stresses induce gene expression of endoplasmic reticulum (ER) chaperones and ER stress sensors. This study demonstrated that regulation of gene expression of ER chaperones and ER stress sensors was induced by EG in rat tissues, and in tissues histological changes are also detected by both staining H&E and immunofluorescent.

• Journal of Life Science
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• v.22 no.2
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• pp.281-284
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• 2012

This study demonstrated that upregulation of gene expression of endoplasmic reticulum (ER) stress chaperones (Bip, ERp29, calnexin, and PDI), ER stress sensors (PERK, ATF6, and Ire1), and cAMP phosphodiesterase 7A1 (cAMP PDE7A1) was induced by ER stresses in FRTL5 cells. While removing A23187 from the culture medium restored upregulation of cAMP PDE7A1 gene expression, removal of thapsigargin did not recover its expression. In addition, cAMP PDE7A1 gene expression was strongly inhibited by treatment with A23187 combined with thyroid stimulating hormone (TSH). The results are the first to show that ER stress induces cAMP PDE7A1 gene expression.

• Molecules and Cells
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• v.47 no.1
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• pp.100001.1-100001.8
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• 2024

In eukaryotes, a primary protein quality control (PQC) process involves the destruction of conformationally misfolded proteins through the ubiquitin-proteasome system. Because approximately one-third of eukaryotic proteomes fold and assemble within the endoplasmic reticulum (ER) before being sent to their destinations, the ER plays a crucial role in PQC. The specific functions and biochemical roles of several E3 ubiquitin ligases involved in ER-associated degradation in mammals, on the other hand, are mainly unknown. We identified 2 E3 ligases, ubiquitin protein ligase E3 component N-recognin 1 (UBR1) and ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which are the key N-recognins in the N-degron pathway and participate in the ER stress response in mammalian cells by modulating their stability. Cells lacking UBR1 and UBR2 are hypersensitive to ER stress-induced apoptosis. Under normal circumstances, these proteins are polyubiquitinated through Lys48-specific linkages and are then degraded by the 26S proteasome. In contrast, when cells are subjected to ER stress, UBR1 and UBR2 exhibit greater stability, potentially as a cellular adaptive response to stressful conditions. Although the precise mechanisms underlying these findings require further investigation, our findings show that cytoplasmic UBR1 and UBR2 have anti-ER stress activities and contribute to global PQC in mammals. These data also reveal an additional level of complexity within the mammalian ER-associated degradation system, implicating potential involvement of the N-degron pathway.

• Molecules and Cells
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• v.41 no.5
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• pp.401-412
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• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• Biomedical Science Letters
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• v.21 no.2
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• pp.126-130
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• 2015

There are several studies that show hypothermia improves cellular ischemia damages on experimental and clinical bases. However, its exact molecular mechanisms are unclear. In this study, we demonstrate that hypothermia induced insulin-like growth factor 1 (IGF1) gene expression, and its expression was dramatically decreased under ischemic insults. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both the phosphorylation of $eIF2{\alpha}$ (eukaryotic translation initiation factor 2 alpha) and ATF6 (activating transcription factor-6) proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. We suggest that hypothermia-treated IGF1 gene expression after ischemia may show a good possibility for the development of treatments and diagnostic methods in cerebral ischemic damages.

• Biomedical Science Letters
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• v.20 no.3
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• pp.168-172
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• 2014

It has recently been shown that hypothermia treatment improves brain ischemia injury and is being increasingly considered by many clinicians. However, the precise roles of hypothermia for brain ischemia are not yet clear. In the present study we demonstrated firstly that hypothermia induced beta-catenin-interacting protein 1 (CTNNBIP1) gene expression and its expression was dramatically decreased under ischemic conditions. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both, the phosphorylation of $eIF2{\alpha}$, and ATF6 proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. These findings suggested that hypothermia controlled CTNNBIP1 gene expression under ischemia, which may provide a clue to the development of treatments and diagnostic methods for brain ischemia.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.441-456
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• 2022

Shiga toxins (Stxs) are major virulence factors from the enterohemorrhagic Escherichia coli (EHEC), a subset of Stx-producing Escherichia coli. Stxs are multi-functional, ribosome-inactivating proteins that underpin the development of hemolytic uremic syndrome (HUS) and central nervous system (CNS) damage. Currently, therapeutic options for the treatment of diseases caused by Stxs are limited and unsatisfactory. Furthermore, the pathophysiological mechanisms underpinning toxin-induced inflammation remain unclear. Numerous works have demonstrated that the various host ribotoxic stress-induced targets including p38 mitogen-activated protein kinase, its downstream substrate Mitogen-activated protein kinase-activated protein kinase 2, and apoptotic signaling via ER-stress sensors are activated in many different susceptible cell types following the regular retrograde transportation of the Stxs, eventually leading to disturbing intercellular communication. Therapeutic options targeting host cellular pathways induced by Stxs may represent a promising strategy for intervention in Stx-mediated acute renal dysfunction, retinal damage, and CNS damage. This review aims at fostering an in-depth understanding of EHEC Stxs-mediated pathogenesis through the toxin-host interactions.