scholarly journals The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Hai Liu ◽  
Jianqiong Yang ◽  
Linfu Li ◽  
Weimei Shi ◽  
Xiaoliang Yuan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Clinical Applications ◽  
Inflammatory Factors ◽  
Ros Production ◽  
Pharmacological Mechanism ◽  
Medical Benefits ◽  
Novel Strategy

ER stress has been implicated in pathophysiological development of many diseases. Persistent overwhelming stimuli trigger ER stress to initiate apoptosis, autophagy, and cell death. IRE1-JNK and eIF2α-CHOP signaling pathways are the two important players of ER stress, which is also modulated by ROS production, calcium disturbance, and inflammatory factors. ER stress has been developed as a novel strategy for diseases management. Recently, a vast of research focuses on the natural occurring compounds targeting ER stress, which results in medical benefits to human diseases. These small reported molecules mainly include polyphenols, alkaloids, and saponins. Many of them have been developed for use in clinical applications. To better understand the pharmacological mechanism of these molecules in ER stress in diseases, efforts have been made to discover and deliver medical merits. In this paper, we will summarize the natural occurring compounds targeting ER stress.

Curcumin induces cell death of human papillary thyroid carcinoma BCPAP cells through endoplasmic reticulum stress

RSC Advances ◽  
2016 ◽  
Vol 6 (58) ◽  
pp. 52905-52912 ◽  
Author(s):  
Lixi Zhang ◽  
Li Zhang ◽  
Xian Cheng ◽  
Yanyan Gao ◽  
Jiandong Bao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Papillary Thyroid Carcinoma ◽  
Endoplasmic Reticulum Stress ◽  
Thyroid Carcinoma ◽  
Er Stress ◽  
Signaling Pathway ◽  
Papillary Thyroid

Curcumin induced cell death of BCPAP cells via ER stress with activation of the ATF6/XBP-1 signaling pathway and Ca2+ release.

scholarly journals Sophorolipid exhibits antifungal activity by ROS mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways in Candida albicans

RSC Advances ◽  
2019 ◽  
Vol 9 (71) ◽  
pp. 41639-41648 ◽  
Author(s):  
Farazul Haque ◽  
Nitish Kumar Verma ◽  
Mohammad Alfatah ◽  
Swati Bijlani ◽  
Mani Shankar Bhattacharyya
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Ros Generation

Sophorolipid induces ROS generation in C. albicans leading to mitochondrial dysfunction and ER stress followed by the release of Ca2+ ions (from the ER lumen) that enter mitochondria and further magnify ROS generation leading to cell death.

scholarly journals Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jennifer L Mamrosh ◽  
Jae Man Lee ◽  
Martin Wagner ◽  
Peter J Stambrook ◽  
Richard J Whitby ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Transcription Factor ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Nuclear Receptor ◽  
Stress Resistance ◽  
Unfolded Protein ◽  
Human Disorders ◽  
Protein Response

Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH-1 induces expression of the kinase Plk3, which phosphorylates and activates the transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution. Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER stress, respectively. LRH-1 agonist treatment increases ER stress resistance and decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER stress resolution that is independent of the UPR, yet equivalently required. Targeting LRH-1 may be beneficial in human disorders associated with chronic ER stress.

scholarly journals Methylglyoxal induces cell death through endoplasmic reticulum stress-associated ROS production and mitochondrial dysfunction

2016 ◽  
Vol 20 (9) ◽  
pp. 1749-1760 ◽  
Author(s):  
Chi-Ming Chan ◽  
Duen-Yi Huang ◽  
Yi-Pin Huang ◽  
Shu-Hao Hsu ◽  
Lan-Ya Kang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Ros Production

scholarly journals Neuroprotective Effects of Exercise Postconditioning After Stroke via SIRT1-Mediated Suppression of Endoplasmic Reticulum (ER) Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Fengwu Li ◽  
Xiaokun Geng ◽  
Hangil Lee ◽  
Melissa Wills ◽  
Yuchuan Ding
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Ros Production ◽  
Post Stroke ◽  
Caspase 12 ◽  
Stress Pathway

While it is well-known that pre-stroke exercise conditioning reduces the incidence of stroke and the development of comorbidities, it is unclear whether post-stroke exercise conditioning is also neuroprotective. The present study investigated whether exercise postconditioning (PostE) induced neuroprotection and elucidated the involvement of SIRT1 regulation on the ROS/ER stress pathway. Adult rats were subjected to middle cerebral artery occlusion (MCAO) followed by either: (1) resting; (2) mild exercise postconditioning (MPostE); or (3) intense exercise postconditioning (IPostE). PostE was initiated 24 h after reperfusion and performed on a treadmill. At 1 and 3 days thereafter, we determined infarct volumes, neurological defects, brain edema, apoptotic cell death through measuring pro- (BAX and Caspase-3) and anti-apoptotic (Bcl-2) proteins, and ER stress through the measurement of glucose-regulated protein 78 (GRP78), inositol-requiring 1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), Caspase-12, and SIRT1. Proteins were measured by Western blot. ROS production was detected by flow cytometry.Compared to resting rats, both MPostE and IPostE significantly decreased brain infarct volumes and edema, neurological deficits, ROS production, and apoptotic cell death. MPostE further increased Bcl-2 expression and Bcl-2/BAX ratio as well as BAX and Caspase-3 expressions and ROS production (*p < 0.05). Both PostE groups saw decreases in ER stress proteins, while MPostE demonstrated a further reduction in GRP78 (***p < 0.001) and Caspase-12 (*p < 0.05) expressions at 1 day and IRE1α (**p < 0.01) and CHOP (*p < 0.05) expressions at 3 days. Additionally, both PostE groups saw significant increases in SIRT1 expression.In this study, both mild and intense PostE levels induced neuroprotection after stroke through SIRT1 and ROS/ER stress pathway. Additionally, the results may provide a base for our future study regarding the regulation of SIRT1 on the ROS/ER stress pathway in the biochemical processes underlying post-stroke neuroprotection. The results suggest that mild exercise postconditioning might play a similar neuroprotective role as intensive exercise and could be an effective exercise strategy as well.

scholarly journals Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Wei-Jiunn Lee ◽  
Ming-Hsien Chien ◽  
Jyh-Ming Chow ◽  
Junn-Liang Chang ◽  
Yu-Ching Wen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Treatment Strategies ◽  
Ros Generation ◽  
Ros Production ◽  
Electron Microscopic ◽  
Cytoplasmic Vacuolation

Abstract The antiapoptotic and antiautophagic abilities of cancer cells constitute a major challenge for anticancer drug treatment. Strategies for triggering nonapoptotic or nonautophagic cell death may improve therapeutic efficacy against cancer. Curcumin has been reported to exhibit cancer chemopreventive properties. Herein, we report that curcumin induced apoptosis in LNCaP, DU145 and PC-3 cells but triggered extensive cytoplasmic vacuolation in PC-3M cells. Electron microscopic images showed that the vacuoles lacked intracellular organelles and were derived from the endoplasmic reticulum (ER). Moreover, curcumin-induced vacuolation was not reversed by an apoptosis- or autophagy-related inhibitor, suggesting that vacuolation-mediated cell death differs from classical apoptotic and autophagic cell death. Mechanistic investigations revealed that curcumin treatment upregulated the ER stress markers CHOP and Bip/GRP78 and the autophagic marker LC3-II. In addition, curcumin induced ER stress by triggering ROS generation, which was supported by the finding that treating cells with the antioxidant NAC alleviated curcumin-mediated ER stress and vacuolation-mediated death. An in vivo PC-3M orthotopic prostate cancer model revealed that curcumin reduced tumor growth by inducing ROS production followed by vacuolation-mediated cell death. Overall, our results indicated that curcumin acts as an inducer of ROS production, which leads to nonapoptotic and nonautophagic cell death via increased ER stress.

CUX1 controls endoplasmic reticulum stress and autophagy related cell death

2016 ◽  
Vol 54 (12) ◽  
pp. 1343-1404
Author(s):  
G Metzger ◽  
P Di Fazio ◽  
DK Bartsch ◽  
T Gress ◽  
TT Wissniowski
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Related Cell

Inhibition of Autophagy Potentiated Hippocampal Cell Death Induced by Endoplasmic Reticulum Stress and its Activation by Trehalose Failed to be Neuroprotective

2019 ◽  
Vol 16 (1) ◽  
pp. 3-11
Author(s):  
Luisa Halbe ◽  
Abdelhaq Rami
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Damage ◽  
Protective Mechanism ◽  
Unfolded Proteins ◽  
Neuronal Viability ◽  
Hippocampal Cell ◽  
Trigger Cell Death ◽  
Autophagy Inhibition

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

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