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https://www.readbyqxmd.com/read/28534505/proteomic-identification-of-erp29-as-a-key-chemoresistant-factor-activated-by-the-aggregating-p53-mutant-arg282trp
#1
Y Zhang, Y Hu, J-L Wang, H Yao, H Wang, L Liang, C Li, H Shi, Y Chen, J-Y Fang, J Xu
Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in (R282W)TP53-expressing cells that were exposed to cisplatin stress...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533271/vhl-inactivation-in-precancerous-kidney-cells-induces-an-inflammatory-response-via-er-stress-activated-ire1%C3%AE-signaling
#2
Chan-Yen Kuo, Chih-Hung Lin, Tien Hsu
Mutations and epigenetic inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) are major causes of clear-cell renal cell carcinoma (ccRCC) that may originate from chronic inflammation. However, the role of VHL loss-of-function in the development of ccRCC via inflammation remains poorly understood. VHL mutant cells exhibit metabolic abnormalities that can cause chronic endoplasmic reticulum (ER) stress and unfolded protein response (UPR). We hypothesize that unresolved ER stress induces the inflammatory responses observed in ccRCC...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28528361/toward-the-identification-and-the-targeting-of-key-players-of-the-mitochondrial-unfolded-protein-response-upr-mt-in-cancer
#3
EDITORIAL
Doris Germain
No abstract text is available yet for this article.
May 20, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28526017/the-effect-of-hypoxia-on-the-lipidome-of-recombinant-pichia-pastoris
#4
Núria Adelantado, Pablo Tarazona, Karlheinz Grillitsch, Xavier García-Ortega, Sergi Monforte, Francisco Valero, Ivo Feussner, Günther Daum, Pau Ferrer
BACKGROUND: Cultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia...
May 19, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28522876/comparative-proteomic-analysis-of-the-mitochondria-associated-er-membrane-mam-in-a-long-term-type-2-diabetic-rodent-model
#5
Jacey Hongjie Ma, Shichen Shen, Joshua J Wang, Zhanwen He, Amanda Poon, Jun Li, Jun Qu, Sarah X Zhang
The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion (SOD) method, and MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#6
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28507517/the-role-of-unfolded-protein-response-and-mitogen-activated-protein-kinase-signaling-in-neurodegenerative-diseases-with-special-focus-on-prion-diseases
#7
REVIEW
Syed Zahid Ali Shah, Deming Zhao, Tariq Hussain, Lifeng Yang
Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrP(Sc)) in the brain. PrP(Sc) accumulation in the endoplasmic reticulum (ER) result in a dysregulated calcium (Ca(2+)) homeostasis and subsequent initiation of unfolded protein response (UPR) leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stress-induced apoptosis are still unclear...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28507169/human-neutrophil-elastase-induces-endothelial-cell-apoptosis-by-activating-the-perk-chop-branch-of-the-unfolded-protein-response
#8
Irina Grechowa, Sven Horke, Anja Wallrath, Christian-Friedrich Vahl, Bernhard Dorweiler
Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing apoptosis in endothelial cells. Our aim was to investigate the proapoptotic mechanism of elastase on endothelial cells and to evaluate the presence of elastase in human plaque material. Human endothelial cells were treated with purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was analyzed by RT-PCR, immunocytochemistry, and Western blot...
May 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28503708/stress-and-the-nonsense-mediated-rna-decay-pathway
#9
REVIEW
Alexandra E Goetz, Miles Wilkinson
Cells respond to internal and external cellular stressors by activating stress-response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences...
May 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28502979/chrysin-ameliorates-podocyte-injury-and-slit-diaphragm-protein-loss-via-inhibition-of-the-perk-eif2%C3%AE-atf-chop-pathway-in-diabetic-mice
#10
Min-Kyung Kang, Sin-Hye Park, Yun-Ho Kim, Eun-Jung Lee, Lucia Dwi Antika, Dong Yeon Kim, Yean-Jung Choi, Young-Hee Kang
Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular filtration barrier via their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys...
May 15, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#11
Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock, Hui Chen
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect.  In this study, we show that offspring born to HFD-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28500182/upr-transducer-bbf2h7-allows-export-of-type-ii-collagen-in-a-cargo-and-developmental-stage-specific-manner
#12
Tokiro Ishikawa, Takuya Toyama, Yuki Nakamura, Kentaro Tamada, Hitomi Shimizu, Satoshi Ninagawa, Tetsuya Okada, Yasuhiro Kamei, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Eriko Aoyama, Masaharu Takigawa, Akihiro Harada, Kazutoshi Mori
The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers. We have found that ER stress occurs physiologically during early embryonic development in medaka fish and that the smooth alignment of notochord cells requires ATF6 as a UPR transducer, which induces ER chaperones for folding of type VIII (short-chain) collagen. After secretion of hedgehog for tissue patterning, notochord cells differentiate into sheath cells, which synthesize type II collagen...
May 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28499833/mitochondrial-dysfunction-in-cancer-potential-roles-of-atf5-and-the-mitochondrial-upr
#13
REVIEW
Pan Deng, Cole M Haynes
Mitochondria form a cellular network of organelles, or cellular compartments, that efficiently couple nutrients to energy production in the form of ATP. As cancer cells rely heavily on glycolysis, historically mitochondria and the cellular pathways in place to maintain mitochondrial activities were thought to be more relevant to diseases observed in non-dividing cells such as muscles and neurons. However, more recently it has become clear that cancers rely heavily on mitochondrial activities including lipid, nucleotide and amino acid synthesis, suppression of mitochondria-mediated apoptosis as well as oxidative phosphorylation (OXPHOS) for growth and survival...
May 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28499449/perk-induces-resistance-to-cell-death-elicited-by-endoplasmic-reticulum-stress-and-chemotherapy
#14
Iris C Salaroglio, Elisa Panada, Enrico Moiso, Ilaria Buondonno, Paolo Provero, Menachem Rubinstein, Joanna Kopecka, Chiara Riganti
BACKGROUND: Nutrient deprivation, hypoxia, radiotherapy and chemotherapy induce endoplasmic reticulum (ER) stress, which activates the so-called unfolded protein response (UPR). Extensive and acute ER stress directs the UPR towards activation of death-triggering pathways. Cancer cells are selected to resist mild and prolonged ER stress by activating pro-survival UPR. We recently found that drug-resistant tumor cells are simultaneously resistant to ER stress-triggered cell death. It is not known if cancer cells adapted to ER stressing conditions acquire a chemoresistant phenotype...
May 12, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28493471/what-role-does-the-stress-response-have-in-congestive-heart-failure
#15
REVIEW
Ahmed Badreddin, Youssef Fady, Hamdy Attia, Mohamed Hafez, Ahmed Khairallah, Dina Johar, Larry Bernstein
This review is concerned with cardiac malfunction as a result of an imbalance in protein proteostasis, the homeostatic balance between protein removal and regeneration in a long remodeling process involving the endoplasmic reticulum (ER) and the unfolded protein response (UPR). The importance of this is of special significance with regard to cardiac function as a high energy requiring muscular organ that has a high oxygen requirement and is highly dependent on mitochondria. The importance of mitochondria is not only concerned with high energy dependence on mitochondrial electron transport, but it also has a role in the signaling between the mitochondria and the ER under stress...
May 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28491820/endoplasmic-reticulum-stress-unfolded-protein-response-and-cancer-cell-fate
#16
REVIEW
Marco Corazzari, Mara Gagliardi, Gian Maria Fimia, Mauro Piacentini
Perturbation of endoplasmic reticulum (ER) homeostasis results in a stress condition termed "ER stress" determining the activation of a finely regulated program defined as unfolded protein response (UPR) and whose primary aim is to restore this organelle's physiological activity. Several physiological and pathological stimuli deregulate normal ER activity causing UPR activation, such as hypoxia, glucose shortage, genome instability, and cytotoxic compounds administration. Some of these stimuli are frequently observed during uncontrolled proliferation of transformed cells, resulting in tumor core formation and stage progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28484232/inhibition-of-sp1-prevents-er-homeostasis-and-causes-cell-death-by-lysosomal-membrane-permeabilization-in-pancreatic-cancer
#17
Patricia Dauer, Vineet K Gupta, Olivia McGinn, Alice Nomura, Nikita S Sharma, Nivedita Arora, Bhuwan Giri, Vikas Dudeja, Ashok K Saluja, Sulagna Banerjee
Endoplasmic reticulum (ER) stress initiates an important mechanism for cell adaptation and survival, named the unfolded protein response (UPR). Severe or chronic/prolonged UPR can breach the threshold for survival and lead to cell death. There is a fundamental gap in knowledge on the molecular mechanism of how chronic ER stress is stimulated and leads to cell death in pancreatic ductal adenocarcinoma (PDAC). Our study shows that downregulating specificity protein 1 (Sp1), a transcription factor that is overexpressed in pancreatic cancer, activates UPR and results in chronic ER stress...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28470001/mtdna-metastasis-and-the-mitochondrial-unfolded-protein-response-upr-mt
#18
REVIEW
Timothy C Kenny, Doris Germain
While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPR(mt)) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR(mt) has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPR(mt) may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPR(mt) do not...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28467788/sphingosine-kinase-2-inhibition-synergises-with-bortezomib-to-target-myeloma-by-enhancing-endoplasmic-reticulum-stress
#19
Craig T Wallington-Beddoe, Melissa K Bennett, Kate Vandyke, Lorena Davies, Julia R Zebol, Paul A B Moretti, Melissa R Pitman, Duncan R Hewett, Andrew C W Zannettino, Stuart M Pitson
The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER stress and the UPR prompted us to examine potential synergy between these agents in myeloma...
April 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28455142/a-fish-oil-diet-induces-mitochondrial-uncoupling-and-mitochondrial-unfolded-protein-response-in-epididymal-white-adipose-tissue-of-mice
#20
Shylesh Bhaskaran, Archana Unnikrishnan, Rojina Ranjit, Rizwan Qaisar, Gavin Pharaoh, Stephanie Matyi, Michael Kinter, Sathyaseelan S Deepa
White adipose tissue (WAT) mitochondrial dysfunction is linked to the pathogenesis of obesity driven insulin resistance. Dietary conditions that alter fat mass are known to affect white adipocyte mitochondrial function, however, the impact of high calorie diets on white adipocyte mitochondria is not fully understood. The aim of this study is to assess the effect of a diet rich in saturated or polyunsaturated fat on mitochondrial unfolded protein response (UPR(mt)), a retrograde signaling response that maintains mitochondrial homeostasis, in epididymal WAT (eWAT)...
April 26, 2017: Free Radical Biology & Medicine
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