Proteomic profile of 4-PBA treated human neuronal cells during ER stress

2018 ◽  
Vol 14 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Bhavneet Kaur ◽  
Ajay Bhat ◽  
Rahul Chakraborty ◽  
Khushboo Adlakha ◽  
Shantanu Sengupta ◽  
...  
Keyword(s):  
Er Stress ◽  
Neuronal Cells ◽  
Proteomic Profile ◽  
Chemical Chaperone ◽  
Human Neuronal Cells

Global proteomics supports the role of 4-PBA as a chemical chaperone in alleviating neurotoxicity during ER stress.

scholarly journals Effects of Jasmonic Acid in ER Stress and Unfolded Protein Response in Tomato Plants

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1031
Author(s):  
Zalán Czékus ◽  
Orsolya Csíkos ◽  
Attila Ördög ◽  
Irma Tari ◽  
Péter Poór
Keyword(s):  
Jasmonic Acid ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Transcript Accumulation ◽  
Chemical Chaperone ◽  
Tomato Plants ◽  
Transcript Levels ◽  
Unfolded Protein ◽  
Protein Response

Endoplasmic reticulum (ER) stress elicits a protective mechanism called unfolded protein response (UPR) to maintain cellular homeostasis, which can be regulated by defence hormones. In this study, the physiological role of jasmonic acid (JA) in ER stress and UPR signalling has been investigated in intact leaves of tomato plants. Exogenous JA treatments not only induced the transcript accumulation of UPR marker gene SlBiP but also elevated transcript levels of SlIRE1 and SlbZIP60. By the application of JA signalling mutant jai1 plants, the role of JA in ER stress sensing and signalling was further investigated. Treatment with tunicamycin (Tm), the inhibitor of N-glycosylation of secreted glycoproteins, increased the transcript levels of SlBiP. Interestingly, SlIRE1a and SlIRE1b were significantly lower in jai1. In contrast, the transcript accumulation of Bax Inhibitor-1 (SlBI1) and SlbZIP60 was higher in jai1. To evaluate how a chemical chaperone modulates Tm-induced ER stress, plants were treated with sodium 4-phenylbutyrate, which also decreased the Tm-induced increase in SlBiP, SlIRE1a, and SlBI1 transcripts. In addition, it was found that changes in hydrogen peroxide content, proteasomal activity, and lipid peroxidation induced by Tm is regulated by JA, while nitric oxide was not involved in ER stress and UPR signalling in leaves of tomato.

scholarly journals Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1231 ◽  
Author(s):  
Kinga Rusinek ◽  
Przemysław Sołek ◽  
Anna Tabęcka-Łonczyńska ◽  
Marek Koziorowski ◽  
Jennifer Mytych
Keyword(s):  
Er Stress ◽  
Neurodegenerative Disorders ◽  
Hippocampal Neurons ◽  
Nitrosative Stress ◽  
Defense Mechanism ◽  
Mapk Pathway ◽  
Apoptotic Cell ◽  
Neuronal Cells ◽  
Lps Challenge

Neuroinflammation is defined as the activation of the brain’s innate immune system in response to an inflammatory challenge and is considered to be a prominent feature of neurodegenerative diseases. The contribution of overactivated neuroglial cells to neuroinflammation and neurodegenerative disorders is well documented, however, the role of hippocampal neurons in the neuroinflammatory process remains fragmentary. In this study, we show for the first time, that klotho acts as a signal transducer between pro-survival and pro-apoptotic crosstalk mediated by ER stress in HT-22 hippocampal neuronal cells during LPS challenge. In control HT-22 cells, LPS treatment results in activation of the IRE1α-p38 MAPK pathway leading to increased secretion of anti-inflammatory IL-10, and thus, providing adaptation mechanism. On the other hand, in klotho-deficient HT-22 cells, LPS induces oxi-nitrosative stress and genomic instability associated with telomere dysfunctions leading to p53/p21-mediated cell cycle arrest and, in consequence, to ER stress, inflammation as well as of apoptotic cell death. Therefore, these results indicate that klotho serves as a part of the cellular defense mechanism engaged in the protection of neuronal cells against LPS-mediated neuroinflammation, emerging issues linked with neurodegenerative disorders.

Abstract 083: Role of Endoplasmic Reticulum Stress in the Subfornical Organ (SFO) in Fluid Balance and Metabolic Effects of Brain Renin-Angiotensin System (RAS) Activation

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fusakazu Jo ◽  
Hiromi Jo ◽  
Aline M Hilzendeger ◽  
Martin D Cassell ◽  
D. T Rutkowski ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Water Intake ◽  
Fluid Balance ◽  
Functional Role ◽  
Metabolic Effects ◽  
Chemical Chaperone ◽  
Reduced Drinking ◽  
The Brain

Endoplasmic reticulum (ER) stress has been identified as an important contributor to neurological diseases and implicated in mediating hypothalamic inflammation and the hypertensive effects of angiotensin II (AngII). We examined the role of ER stress in the metabolic and fluid balance effects of brain AngII in two mouse models: 1) sRA transgenic mice (expressing human renin in neurons and human angiotensinogen in glia and neurons), and 2) DOCA-salt treated C57BL/6J mice. Both DOCA-salt and sRA mice exhibit hyperactivity of the brain RAS, suppression of circulating RAS, hypertension, polydipsia, and an elevated resting metabolic rate (RMR). CCAAT-enhancer-binding protein homologous protein (CHOP), a marker of chronic ER stress, was examined by immunocytochemistry in the brain of both models. CHOP immunoreactivity was evident in the SFO of sRA and DOCA-salt mice but was absent in control and CHOP-/- mice. We infused the ER stress-reducing chemical chaperone tauroursodeoxycholic acid (TUDCA, 5.28 ug/day, or aCSF vehicle) to assess if ER stress is mechanistically related to the hypertension, polydipsia, and elevated RMR observed in both models. In initial studies, ICV TUDCA significantly attenuated the polydipsia (aCSF 20.7±0.9 vs TUDCA 10.8±1.0 mL/day, n=6,2) and RMR (aCSF, 3.38±0.07 vs TUDCA 3.16±0.06 mL O2/100g/min, P<0.05 n=13,11) in the DOCA-salt model. ICV TUDCA had similar effects on the polydipsia in the sRA model (51±10% of aCSF control, P<0.05 n=3,4). In the DOCA-salt model, daily ICV injections of TUDCA (10 days, 5ug/ul) markedly reduced drinking, but polydipsia returned one day after the injections were terminated (n=14,12). Daily ICV injection of another ER stress reducer 4-phenylbutyrate (5ug/ul) also reduced drinking (P<0.05 n=5,4). To assess the functional role of CHOP, we measured RMR and water intake in CHOP-/- mice. Interestingly, CHOP-/- mice exhibited increased baseline RMR (CHOP-/- 0.161±0.010 vs C57 0.140±0.005 kcal/hr, P<0.05 n=10,9). The increase in water intake in response to DOCA-salt was blunted (32.7±0.5 vs 22.8±1.1 ml/day, P<0.05, n=4,5) in CHOP-/- mice. Together these data mechanistically implicate ER stress in the fluid and metabolic responses to increased brain RAS activity and suggest CHOP may play a functional role.

Abstract 1313: Pro-atherogenic Effects Of Lipid Peroxidation Products: Role Of The Unfolded Protein Response

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Elena Vladykoskaya ◽  
Petra Haberzettl ◽  
Yonis Ahmed ◽  
Bradford G Hill ◽  
Srinivas D Sithu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Initiation Factor ◽  
Chemical Chaperone ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Jnk Activation

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are associated with atherosclerosis. Expression of UPR target genes such as activating transcription factor 3 (ATF3) and ATF4 is markedly increased in human atherosclerotic lesions. Staining for these proteins co-localizes with the staining with antibodies that recognize the aldehydic epitopes of oxidized LDL, suggesting that lipid-derived aldehydes could be involved in mediating ER stress and UPR. We examined the role of phospholipid aldehyde, 1-palmitoyl-2-(5-oxovaleroyl)- sn -glycero-3-phosphocholine (POVPC), unsaturated lipid-derived aldehydes- 4-hydroxy, trans -2-nonenal (HNE) and acrolein in the induction of ER-stress and UPR in human aortic endothelial cells (HAEC) and human umbical vein endothelial cells (HUVEC). POVPC, HNE and acrolein (10 –25 μM) increased the phosphorylation of eIF2α (eukaryotic initiation factor-2α) by 1.5–5 fold (P<0.001) and induced its downstream effector proteins - ATF4 (1.5–3.5 fold; P<0.001) and ATF3 (4–10 fold; P<0.0001). Incubation of HAEC with these aldehydes also increased the adhesion of THP-1 cells (monocyte) to HAEC by 1.4–1.6 fold (P<0.01). Moreover, incubation of endothelial cells with POVPC increased the mRNA level of the pro-inflammatory cytokine IL-8 by >25 fold (P<0.0001). Chemical chaperone, phenyl butyric acid (PBA), diminished aldehydes-induced expression of ATF3 and ATF4 proteins, endothelial cell-monocyte adhesion and IL-8 formation by 80–95% (P<0.001). POVPC (10–25 μM) also activated JNK by (3–6 fold) in HAEC. Reduction of POVPC to its corresponding alcohol, 1-palmitoyl-2-(5-hydroxyvaleroyl)- sn -glycero-3-phosphocholine (PHVPC) inhibited JNK activation by 74 ± 14 % (P<0.001). Pharmacological inhibition of JNK, inhibited the aldehyde-induced induction of ATF3 and ATF4 proteins by 70–90 % (P<0.001) but not the phosphorylation of eIF2α, and PBA inhibited the POVPC-induced JNK activation by 85 ± 11 % (P<0.001). These data suggest that lipoprotein oxidation products activate endothelial cells in part by inducing ER-stress and their inflammatory signaling could be attenuated by chemical chaperones of protein folding.

Selective Role of Glutathione in Protecting Human Neuronal Cells From Dopamine-induced Apoptosis

1996 ◽  
Vol 35 (5) ◽  
pp. 571-578 ◽  
Author(s):  
M GABBAY ◽  
M TAUBER ◽  
S PORAT ◽  
R SIMANTOV
Keyword(s):  
Neuronal Cells ◽  
Induced Apoptosis ◽  
Human Neuronal Cells

scholarly journals Fibronectin Overexpression Modulates Formation of Macrophage Foam Cells by Activating SREBP2 Involved in Endoplasmic Reticulum Stress

2015 ◽  
Vol 36 (5) ◽  
pp. 1821-1834 ◽  
Author(s):  
Hansong Du ◽  
Yu Wang ◽  
Zhengfeng Zhang ◽  
Jing Yang ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Foam Cell ◽  
Regulatory Element ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Direct Role ◽  
Chemical Chaperone

Aims: To explore the explicit role of fibronectin (FN) isforms in atherosclerotic lesions and the underlying mechanisms. Methods and Results: Inducible stable expression was performed, and similar results were observed between EDA+FN (FN containing EDA domain) and EDA-FN (FN devoid of EDA domain). FN isforms could trigger endoplasmic reticulum (ER) stress, thereby leading to lipid accumulation in cultured Raw264.7 cells. FN isforms-induced gene expression and lipid accumulation were inhibited by a chemical chaperone 4-phenyl butyric acid (PBA) or by overexpression of the ER chaperone, GRP78/BiP, demonstrating a direct role of ER stress in activation of cholesterol/triglyceride biosynthesis. Moreover, activation of the sterol regulatory element binding protein-2 (SREBP2) was found to be downstream of ER stress, and this activation was affirmed to account for the intracellular accumulation of cholesterol using RNAi technique. Conclusion: our study suggests that enhanced FN in lesions facilitates foam cell formation due to dysregulation of the endogenous sterol response pathway by activation of ER stress, and confirms that EDA+FN has no more pro-atherogenic role than EDA-FN in triggering ER stress.

Abstract 176: Role of Endoplasmic Reticulum Stress in the SFO in Fluid Balance and Metabolic Effects of Brain Renin-Angiotensin System Activation

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Fusakazu Jo ◽  
Hiromi Jo ◽  
Aline M Hilzendeger ◽  
Martin D Cassell ◽  
D. T Rutkowski ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Metabolic Rate ◽  
Er Stress ◽  
Fluid Balance ◽  
Neurological Diseases ◽  
Resting Metabolic Rate ◽  
Metabolic Effects ◽  
Chemical Chaperone ◽  
The Brain

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been identified as important contributors to neurological diseases and have been implicated in mediating hypothalamic inflammation and the hypertensive response to angiotensin II. We examined the role of ER stress and the UPR in the metabolic and fluid balance effects of brain angiotensin in two mouse models: 1) “sRA” transgenic mice (expressing human renin in neurons via the synapsin promoter crossed with human angiotensinogen via its own promoter), and 2) DOCA-salt treated C57BL/6J mice. Both DOCA-salt and sRA mice exhibit hyperactivity of the brain RAS, suppression of circulating RAS, hypertension, polydipsia, and an elevated resting metabolic rate. We examined the accumulation of UPR biomarker CCAAT-enhancer-binding protein homologous protein (CHOP) by immunocytochemistry in the brain of both models. CHOP is considered a marker of chronic ER stress. Increased CHOP immunoreactivity was evident in the subfornical organ (SFO) of sRA mice but was absent in non-transgenic (NT) and CHOP-/- mice. There was also increased CHOP immunoreactivity in the SFO of DOCA-salt mice compared with untreated controls. Next, we infused the ER stress-reducing chemical chaperone tauroursodeoxycholic acid (TUDCA, 5.28 ug/day, or aCSF vehicle) to assess if ER stress is mechanistically related to the hypertension, polydipsia, and elevated resting metabolic rate observed in both models. ICV TUDCA (3-5 day pretreatment then continuously for 3 wks) significantly attenuated the polydipsia (aCSF 20.7±0.9 vs TUDCA 10.8±1.0 mL/day, P<0.05) and metabolic rate (aCSF, 3.38±0.07 vs TUDCA 3.16±0.06 mL O2/100g/min, P<0.05) in the DOCA-salt model. ICV TUDCA (3 wks) had similar effects on the polydipsia in the sRA model (51±10% of aCSF control, P<0.05). DOCA-salt caused (P<0.05) increases in 24 hr mean arterial pressure (MAP) that were unaffected by ICV TUDCA (aCSF baseline 114±3 to 128±4 mmHg with DOCA-salt; TUDCA 117±7 to 129±4). Heart rate responses to DOCA-salt were attenuated (P<0.05) with ICV TUDCA (aCSF baseline 528±10 to 448±15 BPM with DOCA-salt; TUDCA 529±6 to 486±11). Together these data mechanistically implicate ER stress in the fluid and metabolic responses to increased brain RAS activity.

scholarly journals Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain

2015 ◽  
Vol 112 (29) ◽  
pp. 9082-9087 ◽  
Author(s):  
Bora Inceoglu ◽  
Ahmed Bettaieb ◽  
Carlos A. Trindade da Silva ◽  
Kin Sing Stephen Lee ◽  
Fawaz G. Haj ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Er Stress ◽  
Peripheral Nervous System ◽  
Pain Behavior ◽  
Type I ◽  
Chemical Chaperone ◽  
Chemical Inducers

Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes.

The role of ER stress for the pathogenesis of SCA3 in primary cell culture experiment

2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
C Funke ◽  
J Hübener ◽  
H Wolburg ◽  
T Schmidt ◽  
H Toresson ◽  
...  
Keyword(s):  
Cell Culture ◽  
Er Stress ◽  
Primary Cell Culture ◽  
Primary Cell ◽  
Culture Experiment ◽  
Cell Culture Experiment

scholarly journals Confounding Roles of ER Stress and the Unfolded Protein Response in Skeletal Muscle Atrophy

2021 ◽  
Vol 22 (5) ◽  
pp. 2567
Author(s):  
Yann S. Gallot ◽  
Kyle R. Bohnert
Keyword(s):  
Skeletal Muscle ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Smooth Endoplasmic Reticulum ◽  
Skeletal Muscle Atrophy ◽  
Unfolded Protein ◽  
The Individual ◽  
The Unfolded Protein Response ◽  
Protein Response

Skeletal muscle is an essential organ, responsible for many physiological functions such as breathing, locomotion, postural maintenance, thermoregulation, and metabolism. Interestingly, skeletal muscle is a highly plastic tissue, capable of adapting to anabolic and catabolic stimuli. Skeletal muscle contains a specialized smooth endoplasmic reticulum (ER), known as the sarcoplasmic reticulum, composed of an extensive network of tubules. In addition to the role of folding and trafficking proteins within the cell, this specialized organelle is responsible for the regulated release of calcium ions (Ca2+) into the cytoplasm to trigger a muscle contraction. Under various stimuli, such as exercise, hypoxia, imbalances in calcium levels, ER homeostasis is disturbed and the amount of misfolded and/or unfolded proteins accumulates in the ER. This accumulation of misfolded/unfolded protein causes ER stress and leads to the activation of the unfolded protein response (UPR). Interestingly, the role of the UPR in skeletal muscle has only just begun to be elucidated. Accumulating evidence suggests that ER stress and UPR markers are drastically induced in various catabolic stimuli including cachexia, denervation, nutrient deprivation, aging, and disease. Evidence indicates some of these molecules appear to be aiding the skeletal muscle in regaining homeostasis whereas others demonstrate the ability to drive the atrophy. Continued investigations into the individual molecules of this complex pathway are necessary to fully understand the mechanisms.

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