scholarly journals Cold storage induces rat liver pyroptosis by activating endoplasmic reticulum stress response through the ATF6-CHOP pathway

2021 ◽  
Author(s):  
jiang liu ◽  
Tiancheng Liang ◽  
Yong Ni ◽  
De Luo ◽  
Bo Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Liver Injury ◽  
Er Stress ◽  
Rat Liver ◽  
Cold Storage ◽  
Liver Tissue ◽  
Molecular Mechanisms ◽  
Er Stress Response ◽  
Caspase 1

Abstract Aims :Liver injury is a common complication of cold storage (CS), and often constitutes a direct cause for liver transplantation failure. The cellular and molecular mechanisms underlying CS-induced liver injury remain unclear. Recent evidence indicates that pyroptosis plays an important role in multiple pathophysiological processes. Using rat liver tissue and cells as a model, we identified a novel mechanism by which inflammasome-dependent interleukin-1β (IL-1β) activation and hepatocyte pyroptosis mediate CS-induced liver injury.Methods :To induce CS, liver tissue and cells were subjected to storage at 4ºC for 12 and 24 h. Inhibition of endoplasmic reticulum (ER) stress was achieved by RNA silencing. Measurements of caspase-1, caspase-11, and IL-1β were performed.Results: Pyroptosis was activated in CS-treated livers, as evidenced by increased levels of caspase-1 and caspase-11 activity, and the elevated expression of IL-1β. ER stress response was activated as well. Inhibition of ER stress response prevented CS-induced liver pyroptosis and inflammation.Conclusion : Our findings suggest that pyroptosis might be playing an important role in the development of liver injury induced by CS. Overactivated ER stress response, followed by activation of the ATF6-CHOP signaling pathway, might be a novel molecular mechanism involved in CS-induced pyroptosis of liver tissue and cells.

scholarly journals Critical review: involvement of endoplasmic reticulum stress in the aetiology of Alzheimer's disease

Open Biology ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 180024 ◽  
Author(s):  
Shoko Hashimoto ◽  
Takaomi C. Saido
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Mouse Models ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Er Stress Response

The endoplasmic reticulum (ER) stress response is regarded as an important process in the aetiology of Alzheimer's disease (AD). The accumulation of pathogenic misfolded proteins and the disruption of intracellular calcium (Ca 2+ ) signalling are considered to be fundamental mechanisms that underlie the induction of ER stress, leading to neuronal cell death. Indeed, a number of studies have proposed molecular mechanisms linking ER stress to AD pathogenesis based on results from in vitro systems and AD mouse models. However, stress responsivity was largely different between each mouse model, even though all of these models display AD-related pathologies. While several reports have shown elevated ER stress responses in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (Tg) AD mouse models, we and other groups, in contrast, observed no such ER stress response in APP-single-Tg or App -knockin mice. Therefore, it is debatable whether the ER stress observed in APP and PS1 double-Tg mice is due to AD pathology. From these findings, the roles of ER stress in AD pathogenesis needs to be carefully addressed in future studies. In this review, we summarize research detailing the relationship between ER stress and AD, and analyse the results in detail.

scholarly journals Gut bacterial metabolites modulate endoplasmic reticulum stress

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaobo Ke ◽  
Kwontae You ◽  
Matthieu Pichaud ◽  
Henry J. Haiser ◽  
Daniel B. Graham ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Epithelial Cell ◽  
Er Stress ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Protease Inhibition ◽  
Bacterial Metabolites ◽  
Er Stress Response ◽  
Stress Pathway

Abstract Background The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response has been implicated in intestinal inflammation associated with inflammatory bowel disease (IBD), a chronic condition characterized by changes to the mucosa and alteration of the gut microbiota. While the microbiota and microbially derived metabolites have also been implicated in ER stress, examples of this connection remain limited to a few observations from pathogenic bacteria. Furthermore, the mechanisms underlying the effects of bacterial metabolites on ER stress signaling have not been well established. Results Utilizing an XBP1s-GFP knock-in reporter colorectal epithelial cell line, we screened 399 microbiome-related metabolites for ER stress pathway modulation. We find both ER stress response inducers (acylated dipeptide aldehydes and bisindole methane derivatives) and suppressors (soraphen A) and characterize their activities on ER stress gene transcription and translation. We further demonstrate that these molecules modulate the ER stress pathway through protease inhibition or lipid metabolism interference. Conclusions Our study identified novel links between classes of gut microbe-derived metabolites and the ER stress response, suggesting the potential for these metabolites to contribute to gut ER homeostasis and providing insight into the molecular mechanisms by which gut microbes impact intestinal epithelial cell homeostasis.

scholarly journals NOD1/NOD2 and RIP2 Regulate Endoplasmic Reticulum Stress-Induced Inflammation during Chlamydia Infection

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Oanh H. Pham ◽  
Bokyung Lee ◽  
Jasmine Labuda ◽  
A. Marijke Keestra-Gounder ◽  
Mariana X. Byndloss ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Inflammatory Response ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Young Women ◽  
The United States ◽  
Chlamydia Infection ◽  
Er Stress Response

ABSTRACT The inflammatory response to Chlamydia infection is likely to be multifactorial and involve a variety of ligand-dependent and -independent recognition pathways. We previously reported the presence of NOD1/NOD2-dependent endoplasmic reticulum (ER) stress-induced inflammation during Chlamydia muridarum infection in vitro, but the relevance of this finding to an in vivo context is unclear. Here, we examined the ER stress response to in vivo Chlamydia infection. The induction of interleukin 6 (IL-6) production after systemic Chlamydia infection correlated with expression of ER stress response genes. Furthermore, when tauroursodeoxycholate (TUDCA) was used to inhibit the ER stress response, an increased bacterial burden was detected, suggesting that ER stress-driven inflammation can contribute to systemic bacterial clearance. Mice lacking both NOD1 and NOD2 or RIP2 exhibited slightly higher systemic bacterial burdens after infection with Chlamydia. Overall, these data suggest a model where RIP2 and NOD1/NOD2 proteins link ER stress responses with the induction of Chlamydia-specific inflammatory responses. IMPORTANCE Understanding the initiation of the inflammatory response during Chlamydia infection is of public health importance given the impact of this disease on young women in the United States. Many young women are chronically infected with Chlamydia but are asymptomatic and therefore do not seek treatment, leaving them at risk of long-term reproductive harm due to inflammation in response to infection. Our manuscript explores the role of the endoplasmic reticulum stress response pathway initiated by an innate receptor in the development of this inflammation.

scholarly journals Endoplasmic Reticulum (ER) Stress Response Failure in Diseases

2020 ◽  
Vol 30 (9) ◽  
pp. 672-675 ◽  
Author(s):  
Kashi Raj Bhattarai ◽  
Manoj Chaudhary ◽  
Hyung-Ryong Kim ◽  
Han-Jung Chae
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Er Stress Response

scholarly journals Endoplasmic reticulum stress response in the roadway for the effects of non-steroidal anti-inflammatory drugs

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Fernanda L.B. Mügge ◽  
Aristóbolo M. Silva
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Stress Responses ◽  
Endoplasmic Reticulum Stress Response ◽  
The Road ◽  
Er Stress Response ◽  
Mediated Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

AbstractOver the past decade, a handful of evidence has been provided that nonsteroidal anti-inflammatory drugs (NSAIDs) display effects on the homeostasis of the endoplasmic reticulum (ER). Their uptake into cells will eventually lead to activation or inhibition of key molecules that mediate ER stress responses, raising not only a growing interest for a pharmacological target in ER stress responses but also important questions how the ER-stress mediated effects induced by NSAIDs could be therapeutically advantageous or not. We review here the toxicity effects and therapeutic applications of NSAIDs involving the three majors ER stress arms namely PERK, IRE1, and ATF6. First, we provide brief introduction on the well-established and characterized downstream events mediated by these ER stress players, followed by presentation of the NSAIDs compounds and mode of action, and finally their effects on ER stress response. NSAIDs present promising drug agents targeting the components of ER stress in different aspects of cancer and other diseases, but a better comprehension of the mechanisms underlying their benefits and harms will certainly pave the road for several diseases’ therapy.

scholarly journals Endoplasmic Reticulum (ER) Chaperone Regulation and Survival of Cells Compensating for Deficiency in the ER Stress Response Kinase, PERK

2008 ◽  
Vol 283 (25) ◽  
pp. 17020-17029 ◽  
Author(s):  
Yukihiro Yamaguchi ◽  
Dennis Larkin ◽  
Roberto Lara-Lemus ◽  
Jose Ramos-Castañeda ◽  
Ming Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Er Stress Response ◽  
Er Chaperone

scholarly journals Nickel Enhances Zinc-Induced Neuronal Cell Death by Priming the Endoplasmic Reticulum Stress Response

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ken-ichiro Tanaka ◽  
Misato Kasai ◽  
Mikako Shimoda ◽  
Ayane Shimizu ◽  
Maho Kubota ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Stress Response ◽  
Trace Metals ◽  
Er Stress ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Endoplasmic Reticulum Stress Response ◽  
Dependent Manner ◽  
Er Stress Response

Trace metals such as zinc (Zn), copper (Cu), and nickel (Ni) play important roles in various physiological functions such as immunity, cell division, and protein synthesis in a wide variety of species. However, excessive amounts of these trace metals cause disorders in various tissues of the central nervous system, respiratory system, and other vital organs. Our previous analysis focusing on neurotoxicity resulting from interactions between Zn and Cu revealed that Cu2+ markedly enhances Zn2+-induced neuronal cell death by activating oxidative stress and the endoplasmic reticulum (ER) stress response. However, neurotoxicity arising from interactions between zinc and metals other than copper has not been examined. Thus, in the current study, we examined the effect of Ni2+ on Zn2+-induced neurotoxicity. Initially, we found that nontoxic concentrations (0–60 μM) of Ni2+ enhance Zn2+-induced neurotoxicity in an immortalized hypothalamic neuronal cell line (GT1-7) in a dose-dependent manner. Next, we analyzed the mechanism enhancing neuronal cell death, focusing on the ER stress response. Our results revealed that Ni2+ treatment significantly primed the Zn2+-induced ER stress response, especially expression of the CCAAT-enhancer-binding protein homologous protein (CHOP). Finally, we examined the effect of carnosine (an endogenous peptide) on Ni2+/Zn2+-induced neurotoxicity and found that carnosine attenuated Ni2+/Zn2+-induced neuronal cell death and ER stress occurring before cell death. Based on our results, Ni2+ treatment significantly enhances Zn2+-induced neuronal cell death by priming the ER stress response. Thus, compounds that decrease the ER stress response, such as carnosine, may be beneficial for neurological diseases.

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