Endoplasmic reticulum and oxidative stress in immunopathology: understanding the crosstalk between cellular stress and inflammation

Hasnain, Sumaira Z.

doi:10.1002/cti2.1035

Cited by 5 publications

(4 citation statements)

References 5 publications

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“…ER stress has increased more attention as a crucial factor connecting and congregating molecular relationships among oxidative stress, endothelial cell dysfunction, and insulin resistance and, therefore, is considered an auspicious drug target for controlling diabetes and cardiovascular problems. Increasing evidence identifies the cross talk between oxidative stress and ER stress in the pathogenesis of diabetes and its complications [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells

Amin

Rajagru

Sarkar

et al. 2021

Oxidative Medicine and Cellular Longevity

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Endoplasmic reticulum (ER) plays a key role in the folding, modification, and trafficking of proteins. When the homeostasis of the ER is disturbed, un/misfolded proteins accumulate in the ER which leads to ER stress. Sustained ER stress results in apoptosis, which is associated with various diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor in redox homeostasis by regulating various genes associated with detoxification and cell-protective mechanisms. We found that Rosolic acid (RA) treatment dose-dependently activates Nrf2 in endothelial cells using the enzyme fragment complementation assay. The cytoprotective role of RA against ER stress-induced endothelial apoptosis and its molecular mechanism was explored in the present study. The Nrf2 and its target genes, as well as ER stress marker expressions, were measured by qPCR in ER stress-exposed endothelial cells. The contribution of Nrf2 in RA-mediated defense mechanism in endothelial cells was established by knockout studies using Nrf2-CRISPR/Cas9. The treatment with RA to ER stress-induced endothelial cells exhibited activation of Nrf2, as demonstrated by Nrf2 translocation and reduction of ER stress markers. We found that the Nrf2 knockout sensitized the endothelial cells against ER stress, and further, RA failed to mediate its cytoprotective effect. Proteomic studies using LC-MS/MS revealed that among the 1370 proteins detected, we found 296 differentially regulated proteins in ER stress-induced endothelial cells, and RA administration ameliorated 71 proteins towards the control levels. Of note, the ER stress in endothelial cells was attenuated by the treatment with the RA, suggesting the role of the Nrf2 activator in the pathological conditions of ER stress-associated diseases.

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Section: Introductionmentioning

confidence: 99%

Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells

Amin

Rajagru

Sarkar

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Third, ER signaling pathway activation was mediated by lymphoma cells with plasmacytic differentiation. ER stress is obligatory in the modification and trafficking of proteins ( 42 ). In the presence of the triggers, misfolded proteins exceed the rate of protein refolding or degradation, accumulate and induce ER stress ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Hemophagocytic lymphohistiocytosis as an onset of diffuse large B‑cell lymphoma: A case report

et al. 2022

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A 53-year-old male presented with a 1-month history of hyperpyrexia. The clinical manifestations revealed hemophagocytic lymphohistiocytosis (HLH). Although a lymph node biopsy could not be obtained, a bone marrow biopsy revealed the activated B-cell subtype of diffuse large B-cell lymphoma (DLBCL). After being treated with HLH-1994 (dexamethasone and etoposide), a rituximab-containing chemotherapy and target agents involving bortezomib, the patient achieved remission. To understand the molecular profile of patient, next-generation sequencing and MYD88 L265P mutation examinations were performed, and the patient was determined to be positive for the MYD88 L265P mutation. Reports of DLBCL with plasmacytic differentiation and a MYD88 innate immune signal transduction adaptor L265P mutation concurrent with HLH are rare. Early recognition, precise diagnosis and timely therapy are pivotal in improving patient prognosis. Furthermore, molecular profiling enables researchers to develop potential therapies aimed at the activated NF-κB and endoplasmic reticulum stress signaling pathways. The present study highlights this pathogenesis and provides suggestions for further individualized therapeutics.

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“…The aforementioned stress pathways are capable of damaging β cells themselves; however, studies show that they primarily mediate their effects by activating local inflammation that amplifies the damage to the cells ( 192–194 ). Inflammation is a critical immune response that clears pathogens and damaged cells, repairs tissue, and releases molecular mediators that amplify or resolve inflammation ( 195 ).…”

Section: Stress Response Pathways Converge On Activation Of Inflammationmentioning

confidence: 99%

Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis

et al. 2022

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The pathogeneses of the two major forms of diabetes, type 1 and type 2, differ with respect to their major molecular insults (loss of immune tolerance and onset of tissue insulin resistance, respectively). However, evidence suggests that dysfunction and/or death of insulin-producing β-cells is common to virtually all forms of diabetes. Although the mechanisms underlying β-cell dysfunction remain incompletely characterized, recent years have been witness to major advances in our understanding of the molecular pathways that contribute to the demise of the β-cell. Cellular and environmental factors contribute to β-cell dysfunction/loss through the activation of molecular pathways that exacerbate endoplasmic reticulum stress, the integrated stress response, oxidative stress, and impaired autophagy. Whereas many of these stress responsive pathways are interconnected, their individual contributions to glucose homeostasis and β-cell health have been elucidated through the development and interrogation of animal models. In these studies, genetic models and pharmacological compounds have enabled the identification of genes and proteins specifically involved in β-cell dysfunction during diabetes pathogenesis. Here, we review the critical stress response pathways that are activated in β-cells in the context of the animal models.

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Endoplasmic reticulum and oxidative stress in immunopathology: understanding the crosstalk between cellular stress and inflammation

Cited by 5 publications

References 5 publications

Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells

Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells

Hemophagocytic lymphohistiocytosis as an onset of diffuse large B‑cell lymphoma: A case report

Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis

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