scholarly journals The tumorigenic role of DSPP and its potential regulation of the unfolded protein response and ER stress in oral cancer cells

2018 ◽  
Author(s):  
Ioannis Gkouveris ◽  
Nikolaos Nikitakis ◽  
Jaya Aseervatham ◽  
Kalu Ogbureke
Keyword(s):  
Oral Cancer ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Unfolded Protein ◽  
Oral Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis

2015 ◽  
Vol 6 (11) ◽  
pp. 1122-1127 ◽  
Author(s):  
Alpa Sidhu ◽  
Justin R. Miller ◽  
Ashootosh Tripathi ◽  
Danielle M. Garshott ◽  
Amy L. Brownell ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Unfolded Protein ◽  
Oral Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

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.

Sequencing of Argonaute-bound miRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a

2021 ◽  
Author(s):  
Christopher J Fields ◽  
Lu Li ◽  
Nicholas M Hiers ◽  
Tianqi Li ◽  
Peike Sheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Rna Polymerase Ii ◽  
Mirna Biogenesis ◽  
Unfolded Protein ◽  
Colorectal Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

MicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modified Crosslinking, Ligation, and Sequencing of Hybrids on Argonaute (AGO-qCLASH) to identify the targets for TSS-miRNAs in HCT116 colorectal cancer cells with or without DROSHA knockout. We observed that miR-320a hybrids dominate in TSS-miRNA hybrids identified by AGO-qCLASH. Targets for miR-320a are enriched in the eIF2 signaling pathway, a downstream component of the unfolded protein response. Consistently, in miR-320a mimic- and antagomir- transfected cells, differentially expressed genes are enriched in eIF2 signaling. Within the AGO-qCLASH data, we identified the endoplasmic reticulum (ER) chaperone Calnexin as a direct miR-320a target, thus connecting miR-320a to the unfolded protein response. During ER stress, but not amino acid deprivation, miR-320a up-regulates ATF4, a critical transcription factor for resolving ER stress. Our study investigates the targetome of the TSS-miRNAs in colorectal cancer cells and establishes miR-320a as a regulator of unfolded protein response.

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.

scholarly journals Sequencing of Argonaute-bound microRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009934
Author(s):  
Christopher J. Fields ◽  
Lu Li ◽  
Nicholas M. Hiers ◽  
Tianqi Li ◽  
Peike Sheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Differentially Expressed Gene ◽  
Mirna Biogenesis ◽  
Unfolded Protein ◽  
Colorectal Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

MicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modified Crosslinking, Ligation, and Sequencing of Hybrids on Argonaute (AGO-qCLASH) to identify the targets for TSS-miRNAs in HCT116 colorectal cancer cells with or without DROSHA knockout. We observed that miR-320a hybrids dominate in TSS-miRNA hybrids identified by AGO-qCLASH. Targets for miR-320a are enriched for the eIF2 signaling pathway, a downstream component of the unfolded protein response. Consistently, in miR-320a mimic- and antagomir- transfected cells, differentially expressed gene products are associated with eIF2 signaling. Within the AGO-qCLASH data, we identified the endoplasmic reticulum (ER) chaperone calnexin as a direct miR-320a down-regulated target, thus connecting miR-320a to the unfolded protein response. During ER stress, but not amino acid deprivation, miR-320a up-regulates ATF4, a critical transcription factor for resolving ER stress. In summary, our study investigates the targetome of the TSS-miRNAs in colorectal cancer cells and establishes miR-320a as a regulator of unfolded protein response.

scholarly journals Effectors Targeting the Unfolded Protein Response during Intracellular Bacterial Infection

2021 ◽  
Vol 9 (4) ◽  
pp. 705
Author(s):  
Manal H. Alshareef ◽  
Elizabeth L. Hartland ◽  
Kathleen McCaffrey
Keyword(s):  
Bacterial Infection ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Host Defense ◽  
Effector Proteins ◽  
Dual Nature ◽  
Unfolded Protein ◽  
Bacterial Replication ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response (UPR) is a homeostatic response to endoplasmic reticulum (ER) stress within eukaryotic cells. The UPR initiates transcriptional and post-transcriptional programs to resolve ER stress; or, if ER stress is severe or prolonged, initiates apoptosis. ER stress is a common feature of bacterial infection although the role of the UPR in host defense is only beginning to be understood. While the UPR is important for host defense against pore-forming toxins produced by some bacteria, other bacterial effector proteins hijack the UPR through the activity of translocated effector proteins that facilitate intracellular survival and proliferation. UPR-mediated apoptosis can limit bacterial replication but also often contributes to tissue damage and disease. Here, we discuss the dual nature of the UPR during infection and the implications of UPR activation or inhibition for inflammation and immunity as illustrated by different bacterial pathogens.

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