Activation of ER stress and apoptosis by α- and β-zearalenol in HCT116 cells, protective role of Quercetin

Melatonin has diverse roles as a signaling molecule that activates a number of downstream defense systems against various biotic and abiotic stresses in plants. However, there have been no reports regarding a direct protective role of melatonin against endoplasmic reticulum (ER) stress. Here, we report that exogenous melatonin treatment attenuated ER stress damage by preserving ER structure and enhancing secretory protein folding capacity in response to tunicamycin treatment. Further transgenic experiments indicated that melatonin-deficient snat1 mutant was hypersensitive to ER stress, whereas melatonin-proficient SNAT1 overexpression (OE) was tolerant to ER stress, as evidenced by reduced ion leakage and higher transcript levels of ER chaperones, including luminal binding protein (BIP) 2, BIP3, and CNX1, compared to wild-type controls. Moreover, this melatonin-mediated ER stress tolerance was dependent on the bZIP60 transcription factor and mitogen-activated protein kinase. Our data suggest that melatonin is actively involved in maintaining homeostasis of the ER during normal plant growth, and also has a protective effect against many environmental stressors that induce ER stress.

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Endoplasmic reticulum chaperone BiP/GRP78 knockdown leads to autophagy and cell death of arginine vasopressin neurons in mice

Scientific Reports ◽

10.1038/s41598-020-76839-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yohei Kawaguchi ◽

Daisuke Hagiwara ◽

Takashi Miyata ◽

Yuichi Hodai ◽

Junki Kurimoto ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Arginine Vasopressin ◽

Urine Volume ◽

Neuronal Loss ◽

Protective Role ◽

Unfolded Protein ◽

The Unfolded Protein Response ◽

Vasopressin Neurons

AbstractThe immunoglobulin heavy chain binding protein (BiP), also referred to as 78-kDa glucose-regulated protein (GRP78), is a pivotal endoplasmic reticulum (ER) chaperone which modulates the unfolded protein response under ER stress. Our previous studies showed that BiP is expressed in arginine vasopressin (AVP) neurons under non-stress conditions and that BiP expression is upregulated in proportion to the increased AVP expression under dehydration. To clarify the role of BiP in AVP neurons, we used a viral approach in combination with shRNA interference for BiP knockdown in mouse AVP neurons. Injection of a recombinant adeno-associated virus equipped with a mouse AVP promoter and BiP shRNA cassette provided specific BiP knockdown in AVP neurons of the supraoptic (SON) and paraventricular nuclei (PVN) in mice. AVP neuron-specific BiP knockdown led to ER stress and AVP neuronal loss in the SON and PVN, resulting in increased urine volume due to lack of AVP secretion. Immunoelectron microscopy of AVP neurons revealed that autophagy was activated through the process of AVP neuronal loss, whereas no obvious features characteristic of apoptosis were observed. Pharmacological inhibition of autophagy by chloroquine exacerbated the AVP neuronal loss due to BiP knockdown, indicating a protective role of autophagy in AVP neurons under ER stress. In summary, our results demonstrate that BiP is essential for the AVP neuron system.

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Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0340-1 ◽

2019 ◽

Vol 51 (11) ◽

pp. 1-16 ◽

Cited By ~ 6

Author(s):

Ye-Ryung Kim ◽

Eun-Ji Lee ◽

Kyong-Oh Shin ◽

Min Hee Kim ◽

Yael Pewzner-Jung ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Stress Response ◽

Er Stress ◽

Acyl Chain ◽

Protective Role ◽

Sphingolipid Metabolism ◽

Er Stress Response ◽

Triglyceride Accumulation ◽

Ceramide Synthases

Abstract The endoplasmic reticulum (ER) is not only important for protein synthesis and folding but is also crucial for lipid synthesis and metabolism. In the current study, we demonstrate an important role of ceramide synthases (CerS) in ER stress and NAFLD progression. Ceramide is important in sphingolipid metabolism, and its acyl chain length is determined by a family of six CerS in mammals. CerS2 generates C22-C24 ceramides, and CerS5 or CerS6 produces C16 ceramide. To gain insight into the role of CerS in NAFLD, we used a high-fat diet (HFD)-induced NAFLD mouse model. Decreased levels of CerS2 and increased levels of CerS6 were observed in the steatotic livers of mice fed a HFD. In vitro experiments with Hep3B cells indicated the protective role of CerS2 and the detrimental role of CerS6 in the ER stress response induced by palmitate treatment. In particular, CerS6 overexpression increased sterol regulatory element-binding protein-1 (SREBP-1) cleavage with decreased levels of INSIG-1, leading to increased lipogenesis. Blocking ER stress abrogated the detrimental effects of CerS6 on palmitate-induced SREBP-1 cleavage. In accordance with the protective role of CerS2 in the palmitate-induced ER stress response, CerS2 knockdown enhanced ER stress and SREBP-1 cleavage, and CerS2 heterozygote livers exhibited a stronger ER stress response and higher triglyceride levels following HFD. Finally, treatment with a low dose of bortezomib increased hepatic CerS2 expression and protected the development of NAFLD following HFD. These results indicate that CerS and its derivatives impact hepatic ER stress and lipogenesis differently and might be therapeutic targets for NAFLD.

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Sa1555 Protective Role of 4-Phenyl Butyric Acid Treatment on Acetaminophen-Induced ER Stress and Oxidative Stress in Mouse Liver

Gastroenterology ◽

10.1016/s0016-5085(16)33598-3 ◽

2016 ◽

Vol 150 (4) ◽

pp. S1065

Author(s):

Kazuyoshi Kon ◽

Hiromi Kusama ◽

Kenichi Ikejima ◽

Kumiko Arai ◽

Tomonori Aoyama ◽

...

Keyword(s):

Oxidative Stress ◽

Er Stress ◽

Butyric Acid ◽

Mouse Liver ◽

Acid Treatment ◽

Protective Role ◽

And Oxidative Stress

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The protective role of YAP1 on ER stress-induced cell death in vascular smooth muscle cells

European Journal of Pharmacology ◽

10.1016/j.ejphar.2017.09.033 ◽

2017 ◽

Vol 815 ◽

pp. 470-477 ◽

Cited By ~ 7

Author(s):

Akira Takaguri ◽

Takashi Kubo ◽

Masaya Mori ◽

Kumi Satoh

Keyword(s):

Cell Death ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Er Stress ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Protective Role

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Protective Role of Fucoidan on Cisplatin-mediated ER Stress in Renal Proximal Tubule Epithelial Cells

Anticancer Research ◽

10.21873/anticanres.13744 ◽

2019 ◽

Vol 39 (10) ◽

pp. 5515-5524 ◽

Cited By ~ 5

Author(s):

HYUNG JOO KIM ◽

YEO MIN YOON ◽

JUN HEE LEE ◽

SANG HUN LEE

Keyword(s):

Epithelial Cells ◽

Er Stress ◽

Proximal Tubule ◽

Protective Role ◽

Renal Proximal Tubule

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Glucocorticoid-activated IRE1α/XBP-1s signaling: an autophagy-associated protective pathway against endotheliocyte damage

AJP Cell Physiology ◽

10.1152/ajpcell.00009.2018 ◽

2018 ◽

Vol 315 (3) ◽

pp. C300-C309 ◽

Cited By ~ 3

Author(s):

Yanchun Gao ◽

Hongyi Zhu ◽

Fan Yang ◽

Qiyang Wang ◽

Yong Feng ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Er Stress ◽

Protective Role ◽

Cellular Damage ◽

Inhibition Of Proliferation ◽

Downstream Signaling ◽

Induced Apoptosis ◽

And Function

Glucocorticoid-induced endothelial injury has been reported in several diseases. Although there are several theories, the exact mechanism underlying the role of glucocorticoids in this process remains unclear. Autophagy has been reported to occur as a response to different stimuli and can affect cell survival and function. In this study, we found that glucocorticoids induced apoptosis and endoplasmic reticulum (ER) stress in endotheliocytes. Furthermore, we discovered that glucocorticoids induced autophagy in these cells and the inositol requiring protein 1 (IRE1α)/X-box binding protein 1s (XBP-1s) axis, one of the downstream signaling pathways of ER stress, was associated with the glucocorticoid-induced autophagy. The autophagy partly protected endotheliocytes from glucocorticoid-induced apoptosis and inhibition of proliferation. In conclusion, glucocorticoid-induced endoplasmic reticulum stress activated the IRE1α/XBP-1s signaling and induced autophagy, which, in turn, played a protective role in endotheliocyte survival and proliferation, avoiding further cellular damage caused by glucocorticoids.

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