Crosstalk between endoplasmic reticulum stress and oxidative stress in apoptosis induced by α-tocopheryl succinate in human gastric carcinoma cells

α-Tocopheryl succinate (α-TOS) has been shown to be a potent apoptosis inducer and growth inhibitor in a variety of cancer cells. Our previous studies showed the important role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the apoptosis induced by α-TOS. However, the relationship of oxidative stress with ER stress is still controversial. The objective of the present study was to investigate the interplay between the two stress responses induced by α-TOS in SGC-7901 human gastric cancer cells. In response to α-TOS, cytological changes typical of apoptosis, induction of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein transcription factor (CHOP), and activation of caspase-4 were observed. And the antioxidant N-acetyl-l-cysteine inhibited induction of both GRP78 and CHOP by α-TOS transcriptionally and translationally. Furthermore, knocking down CHOP by RNA interference decreased ROS generation, increased glutathione level and induced glutathione peroxidase mRNA expression in α-TOS-treated cells, whereas catalase and superoxide dismutases mRNA expression were not altered. The results imply that α-TOS induces ER stress response through ROS production, while CHOP perturbs the redox state of SGC-7901 cells treated with α-TOS.

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Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03756-3 ◽

2021 ◽

Author(s):

Sinan Xiong ◽

Wee-Joo Chng ◽

Jianbiao Zhou

Keyword(s):

Oxidative Stress ◽

Multiple Myeloma ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Cell Fate ◽

Stress Responses ◽

Plasma Cells ◽

Reactive Oxygen Species Generation ◽

Future Research ◽

And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

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Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras‐Raf‐MAPK signalling

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.16237 ◽

2020 ◽

Author(s):

Yongye Huang ◽

Kexun Yuan ◽

Meifang Tang ◽

Jiaming Yue ◽

Lijun Bao ◽

...

Keyword(s):

Gastric Cancer ◽

Er Stress ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Mapk Signalling

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PERK mediates oxidative stress and adipogenesis in Graves’ orbitopathy pathogenesis

Journal of Molecular Endocrinology ◽

10.1530/jme-21-0057 ◽

2021 ◽

Author(s):

JaeSang Ko ◽

Ji-Young Kim ◽

Min Kyung Chae ◽

Eun Jig Lee ◽

Jin Sook Yoon

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Endoplasmic Reticulum ◽

Transcription Factor ◽

Er Stress ◽

Adipogenic Differentiation ◽

Ros Generation ◽

Mrna Levels ◽

Graves Orbitopathy ◽

Orbital Fibroblasts

We examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves’ orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress related genes in orbital tissue harvested from individuals with or without GO was studied using real-time polymerase chain reaction. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts. Intracellular reactive oxygen species (ROS) levels induced in response to cigarette smoke extract (CSE) or hydrogen peroxide were measured using 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. Cells were stained with Oil Red O, and adipogenesis-related transcription factor expression was evaluated through western blotting after adipogenic differentiation. PERK, activating transcription factor 4 (ATF4), and CCAAT-enhancer-binding protein (C/EBP)-homologous protein(CHOP)mRNA levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. PERK silencing inhibited CSE- or hydrogen peroxide-induced ROS generation. After adipogenic differentiation, GO orbital fibroblasts revealed decreased lipid droplets and downregulation of C/EBPα, C/EBPβ, and peroxisome proliferator-activator gamma (PPARγ) in PERK siRNA-transfected cells. The orbital tissues of patients with GO were exposed to chronic ER stress and subsequently exhibited enhanced unfolded protein response (especially through the PERK pathway). PERK silencing reduced oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. Our results imply that PERK-modulating agents can potentially be used to manage GO.

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