Endoplasmic Reticulum Stress-Mediated Signaling Pathway of Gastric Cancer Apoptosis

Xu, Yuehua; You, Yan-Wen; Ren, Xiaochuan; Ding, Yi; Cao, Jing; Zang, Weidong; Feng, Ruo; Zhang, Qinxian

doi:10.5754/hge12369

Cited by 5 publications

(6 citation statements)

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“…The ER is a central cellular organelle in which transmembrane and secretory proteins are synthesized, folded, and matured [37] . The ultrastructural changes we observed in the ER always accompany "ER stress" [38][39][40] . For example, Hanoch et al [38] reported that dilated ER lumen accompanied the response to ER stress in Trypanosoma brucei.…”

Section: Discussionmentioning

confidence: 79%

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

et al. 2014

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Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the highfat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.

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Section: Discussionmentioning

confidence: 79%

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

et al. 2014

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“…Conversely, if the stress exceeds the threshold that GC cells can afford, apoptosis may be initiated. For instance, following treatment with 10 µg/ml tunicamycin for 24 h, GRP78 and CHOP were upregulated whereas Bcl-2 was downregulated in the GC cell line BGC823, ultimately leading to apoptosis (60). Vitamin E succinate (RRR-α-tocopheryl succinate; VES) causes cytological changes typical of apoptosis by increasing ER dilation and cytosolic Ca 2+ concentration.…”

Section: Gc Cell Proliferation Under Hypoxia Stress a Protein Kinasementioning

confidence: 99%

Endoplasmic reticulum chaperone glucose-regulated proteinï¿½78 in gastric cancer: An emerging biomarker (Review)

Wang

Zhang

et al. 2018

Oncol Lett

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The endoplasmic reticulum (ER) is the principal organelle responsible for the synthesis, initial post-translational modification, folding, export and secretion of proteins. It is also responsible for the maintenance of cellular homeostasis. In response to cellular stress conditions including glucose deprivation, hypoxia and changes in calcium homeostasis, ER stress machinery is activated and triggers the unfolded protein response, resulting in the restoration of homeostasis or activation of cell death. Glucose-regulated protein 78 (GRP78), a molecular chaperone, may be induced by ER stress at the transcriptional and translational level. A number of studies have demonstrated that GRP78 serves an important role in tumor cell proliferation, metastasis, angiogenesis and drug-resistance. The present review systematically describes the association between GRP78 expression and gastric cancer pathogenesis, and emphasizes that GRP78 is a novel diagnostic and therapeutic biomarker of gastric cancer.

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“…CHOP is a significant mediator of apoptosis in ER stress 17. Researchers have found that CHOP deletion protects IOP elevation in glucocorticoid-induced ocular hypertension18 and promotes RGCs19 and β cells20 survival in an optic nerve crush mouse model and diabetic mouse model.…”

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confidence: 99%

Endoplasmic Reticulum Stress Response of Trabecular Meshwork Stem Cells and Trabecular Meshwork Cells and Protective Effects of Activated PERK Pathway

Wang

Osakue

Yang

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PurposeThis study aimed to investigate the differential responses of trabecular meshwork stem cells (TMSCs) and trabecular meshwork (TM) cells to endoplasmic reticulum (ER) stress inducers.MethodsHuman TM cells and TMSCs were exposed to tunicamycin, brefeldin A, or thapsigargin. Cell apoptosis was evaluated by flow cytometry. ER stress markers were detected by quantitative PCR, Western blotting, and immunostaining. Morphologic changes were evaluated by transmission electron microscopy. Cells were treated with the PERK inhibitor GSK2606414 or the elF2α dephosphorylation inhibitor Salubrinal together with tunicamycin to evaluate their effects on ER stress.ResultsBoth TMSCs and TM cells underwent apoptosis after 48- and 72-hour treatment with ER stress inducers. ER stress triggered the unfolded protein response (UPR) with increased expression of GRP78, sXBP1, and CHOP, which was significantly lower in TMSCs than TM cells. Swollen ER and mitochondria were detected in both TMSCs and TM cells. Neither GSK2606414 nor salubrinal alone activated UPR. GSK2606414 significantly reduced cell survival rates after tunicamycin treatment, and salubrinal increased cell survival rates. The increased expression of GRP78, sXBP1, CHOP, and GADD34 peaked at 6 or 12 hours and lasted longer in TM cells than TMSCs. Salubrinal treatment dramatically increased OCT4 and CHI3L1 expression in TMSCs.ConclusionsIn response to ER stress inducers, TMSCs activated a lower level of UPR and lasted shorter than TM cells. Inhibition of elF2α dephosphorylation had a protective mechanism against cell death. Stem cells combined with salubrinal may be a more effective way for TM regeneration in glaucoma.

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Endoplasmic Reticulum Stress-Mediated Signaling Pathway of Gastric Cancer Apoptosis

Abstract: TM can induce ESR and regulate downstream molecules CHOP up-regulation and Bcl-2 down-regulation which lead to BGC823 apoptosis. This study may provide a new theoretical basis for the pathogenesis of gastric cancer.

Cited by 5 publications

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Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

Endoplasmic reticulum chaperone glucose-regulated proteinï¿½78 in gastric cancer: An emerging biomarker (Review)

Endoplasmic Reticulum Stress Response of Trabecular Meshwork Stem Cells and Trabecular Meshwork Cells and Protective Effects of Activated PERK Pathway

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