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unfolded protein response

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https://www.readbyqxmd.com/read/28526017/the-effect-of-hypoxia-on-the-lipidome-of-recombinant-pichia-pastoris
#1
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
#2
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/28521011/translation-initiation-events-on-structured-eukaryotic-mrnas-generate-gene-expression-noise
#3
Estelle Dacheux, Naglis Malys, Xiang Meng, Vinoy Ramachandran, Pedro Mendes, John Eg McCarthy
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem-loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#4
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/28509380/amyloid-is-essential-but-insufficient-for-alzheimer-causation-addition-of-subcellular-cofactors-is-required-for-dementia
#5
REVIEW
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
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
#6
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
#7
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/28507004/choosing-the-right-response-to-er-stress
#8
Ben Short
Cells use distinct unfolded protein response transducers to export different collagens during development.
May 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28504640/the-sec61-translocon-limits-ire1%C3%AE-signaling-during-the-unfolded-protein-response
#9
Arunkumar Sundaram, Rachel Plumb, Suhila Appathurai, Malaiyalam Mariappan
IRE1α is an endoplasmic reticulum (ER) localized endonuclease activated by misfolded proteins in the ER. Previously, we demonstrated that IRE1α forms a complex with the Sec61 translocon, to which its substrate XBP1u mRNA is recruited for cleavage during ER stress (Plumb et al., 2015). Here, we probe IRE1α complexes in cells with blue native PAGE immunoblotting. We find that IRE1α forms a hetero-oligomeric complex with the Sec61 translocon that is activated upon ER stress with little change in the complex...
May 15, 2017: ELife
https://www.readbyqxmd.com/read/28503708/stress-and-the-nonsense-mediated-rna-decay-pathway
#10
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
#11
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/28502485/low-crowding-agent-concentration-destabilizes-against-pressure-unfolding
#12
J Somkuti, Z Török, F Pfalzgraf, L Smeller
The concentration of macromolecules inside a cell is very high, which can affect the behavior of the enzymes, and consequently influence vital biological processes. This is called macromolecular crowding. Since the most important effect of macromolecular crowding is the excluded volume, we performed pressure experiments, where the volume (as conjugate parameter to the pressure) is the crucial factor. We measured the temperature and pressure stability of bovine serum albumin and lysozyme with various concentrations of crowding agents, dextran, Ficoll™ and lysozyme itself...
May 1, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28500697/light-induced-conformational-changes-in-the-plant-cryptochrome-photolyase-homology-region-resolved-by-selective-isotope-labeling-and-infrared-spectroscopy
#13
Constanze Sommer, Marina S Dietz, Thomas Patschkowski, Tilo Mathes, Tilman Kottke
Plant cryptochromes are photoreceptors that regulate flowering, circadian rhythm and photomorphogenesis in response to blue and UV-A light. It has been demonstrated that the oxidized flavin cofactor is photoreduced to the neutral radical state via separate electron and proton transfer. Conformational changes have been found in the C-terminal extension, but few studies have addressed the changes in secondary structure in the sensory photolyase homology region (PHR). Here, we investigated the PHR of the plant cryptochrome from the green alga Chlamydomonas reinhardtii by light-induced infrared difference spectroscopy in combination with global (13) C and (15) N isotope labeling...
May 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#14
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
#15
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
#16
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
#17
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/28498407/respiratory-syncytial-virus-infection-accelerates-lung-fibrosis-through-the-unfolded-protein-response-in-a-bleomycin-induced-pulmonary-fibrosis-animal-model
#18
Lina Wang, Wei Cheng, Zhimin Zhang
Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28498401/luteolin-induced-apoptosis-through-activation-of-endoplasmic-reticulum-stress-sensors-in-pheochromocytoma-cells
#19
Kisang Kwon, Young-Sook Kwon, Seung-Whan Kim, Kweon Yu, Kyung-Ho Lee, O-Yu Kwon
Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits tumor cell proliferation, inflammatory and oxidative stress better, when compared with other flavonoids. In the present study, it was demonstrated that luteolin induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic bodies. In addition, luteolin regulates expression of the endoplasmic reticulum (ER) chaperone binding immunoglobulin protein, activating ER stress sensors (eukaryotic initiation factor 2α phosphorylation and X‑box binding protein 1 mRNA splicing) and induced autophagy...
May 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28496018/effects-of-heat-stress-on-bovine-preimplantation-embryos-produced-in-vitro
#20
Miki Sakatani
Summer heat stress decreases the pregnancy rate in cattle and has been thought to be associated with the early embryonic death caused by the elevation of maternal body temperature. In vitro cultures have been widely used for the evaluation of effects of heat stress on oocytes, fertilization, preimplantation, and embryonic development. Susceptibility to heat stress is present in developmental stages from oocytes to cleavage-stage (before embryonic gene activation, EGA) embryos, leading to a consequent decrease in developmental competence...
May 12, 2017: Journal of Reproduction and Development
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