keyword
MENU ▼
Read by QxMD icon Read
search

unfolded protein response

keyword
https://www.readbyqxmd.com/read/28636534/novel-tropolones-induce-the-unfolded-protein-response-pathway-and-apoptosis-in-multiple-myeloma-cells
#1
Staci L Haney, Cheryl Allen, Michelle L Varney, Kaitlyn M Dykstra, Eric R Falcone, Sean H Colligan, Qiang Hu, Alyssa M Aldridge, Dennis L Wright, Andrew J Wiemer, Sarah A Holstein
Tropolones are small organic compounds with metal-directing moieties. Tropolones inhibit the proliferation of cancer cell lines, possibly through their effects on metalloenzymes such as select histone deacetylases (HDACs). Pan-HDAC inhibitors are therapeutically beneficial in the treatment of multiple myeloma, however there is interest in the use of more selective HDAC inhibitor therapy to minimize adverse side effects. We hypothesized that tropolones might have anti-myeloma activities. To this end, a series of novel α-substituted tropolones were evaluated for effects on multiple myeloma cells...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#2
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28633019/edem-function-in-erad-protects-against-chronic-er-proteinopathy-and-age-related-physiological-decline-in-drosophila
#3
Michiko Sekiya, Akiko Maruko-Otake, Stephen Hearn, Yasufumi Sakakibara, Naoki Fujisaki, Emiko Suzuki, Kanae Ando, Koichi M Iijima
The unfolded protein response (UPR), which protects cells against accumulation of misfolded proteins in the ER, is induced in several age-associated degenerative diseases. However, sustained UPR activation has negative effects on cellular functions and may worsen disease symptoms. It remains unknown whether and how UPR components can be utilized to counteract chronic ER proteinopathies. We found that promotion of ER-associated degradation (ERAD) through upregulation of ERAD-enhancing α-mannosidase-like proteins (EDEMs) protected against chronic ER proteinopathy without inducing toxicity in a Drosophila model...
June 19, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28631090/subclinical-cutaneous-inflammation-remained-after-permeability-barrier-disruption-enhances-uv-sensitivity-by-altering-er-stress-responses-and-topical-pseudoceramide-prevents-them
#4
Sang Eun Lee, Yutaka Takagi, Takahiro Nishizaka, Ji Hwoon Baek, Han Jo Kim, Seung Hun Lee
Stratum corneum forms the UV barrier. The effect of ultraviolet B (UVB) on normal skin was extensively studied; however, its effect on barrier perturbed skin remains undefined. Both barrier perturbation and UVB irradiation induce endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in keratinocytes. Mild ER stress activates homeostatic UPR, while severe ER stress leads to abnormal UPR, promoting apoptosis and inflammation. Here, we investigated UV sensitivity and UVB-induced UPR in barrier-disrupted human skin and the effects of pseudoceramide-dominant emollient on UVB-induced skin responses...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28630146/er-stress-causes-widespread-protein-aggregation-and-prion-formation
#5
Norfadilah Hamdan, Paraskevi Kritsiligkou, Chris M Grant
Disturbances in endoplasmic reticulum (ER) homeostasis create a condition termed ER stress. This activates the unfolded protein response (UPR), which alters the expression of many genes involved in ER quality control. We show here that ER stress causes the aggregation of proteins, most of which are not ER or secretory pathway proteins. Proteomic analysis of the aggregated proteins revealed enrichment for intrinsically aggregation-prone proteins rather than proteins which are affected in a stress-specific manner...
June 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28628644/targeting-multiple-pro-apoptotic-signaling-pathways-with-curcumin-in-prostate-cancer-cells
#6
Mariela Rivera, Yanilda Ramos, Madeline Rodríguez-Valentín, Sheila López-Acevedo, Luis A Cubano, Jin Zou, Qiang Zhang, Guangdi Wang, Nawal M Boukli
Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28628040/lipogenic-transcription-factor-chrebp-mediates-fructose-induced-metabolic-adaptations-to-prevent-hepatotoxicity
#7
Deqiang Q Zhang, Xin Tong, Kyle VanDommelen, Neil Gupta, Kenneth Stamper, Graham F Brady, Zhuoxian Meng, Jiandie D Lin, Liangyou Y Rui, M Bishr Omary, Lei Yin
Epidemiologic and animal studies implicate overconsumption of fructose in the development of nonalcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remain largely unknown. Here, we have presented evidence supporting the essential function of the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) in mediating adaptive responses to fructose and protecting against fructose-induced hepatotoxicity. In WT mice, a high-fructose diet (HFrD) activated hepatic lipogenesis in a ChREBP-dependent manner; however, in Chrebp-KO mice, a HFrD induced steatohepatitis...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627018/the-nucleotide-free-state-of-heterotrimeric-g-proteins-%C3%AE-subunit-adopts-a-highly-stable-conformation
#8
Sai Krishna Andhirka, Ravichandran Vignesh, Gopala Krishna Aradhyam
Deciphering the mechanism of activation of heterotrimeric G proteins by their cognate receptors continues to be an intriguing area of research. The recently solved crystal structure of the ternary complex captured the receptor-bound α-subunit in an open conformation, without bound nucleotide has improved our understanding of the activation process. Despite these advancements, the mechanism by which the receptor causes GDP release from the α-subunit remains elusive. To elucidate the mechanism of activation, we studied guanine nucleotide-induced structural stability of the α-subunit (in response to thermal/chaotrope-mediated stress)...
June 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#9
Hui Han, Yuxin He, Jay Hu, Rhema Lau, Harrison Lee, Cheng Ji
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes...
April 2017: Hepatol Commun
https://www.readbyqxmd.com/read/28625916/er-stress-disturbs-sr-er-mitochondria-ca-2-transfer-implications-in-duchenne-muscular-dystrophy
#10
Marion Pauly, Claire Angebault-Prouteau, Haikel Dridi, Cécile Notarnicola, Valérie Scheuermann, Alain Lacampagne, Stefan Matecki, Jérémy Fauconnier
Besides its role in calcium (Ca(2+)) homeostasis, the sarco-endoplamic reticulum (SR/ER) controls protein folding and is tethered to mitochondria.Under pathophysiological conditions the unfolded protein response (UPR) is associated with disturbance in SR/ER-mitochondria crosstalk. Here, we investigated whether ER stress altered SR/ER-mitochondria links, Ca(2+) handling and muscle damage in WT (Wild Type) and mdx mice, the murine model of Duchenne Muscular Dystrophy (DMD). In WT mice, the SR/ER-mitochondria links were decreased in isolated FDB muscle fibers after injection of ER stress activator tunicamycin (TM)...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28625789/maltoporin-lamb-unfolds-%C3%AE-hairpins-along-mechanical-stress-dependent-unfolding-pathways
#11
Johannes Thoma, Noah Ritzmann, Dominik Wolf, Estefania Mulvihill, Sebastian Hiller, Daniel J Müller
Upon mechanical pulling at either terminal end, β barrel outer membrane proteins stepwise unfold β strands or β hairpins until entirely extracted from the membrane. This unique unfolding pathway has been described for β barrels comprising 8, 14, or 22 β strands. Here we mechanically unfold the 18-stranded β barrel outer membrane protein LamB from Escherichia coli. We find that its mechanical unfolding pathway is shaped by the stepwise unfolding of β hairpins. However, we also observe that β hairpins can unfold groupwise...
June 6, 2017: Structure
https://www.readbyqxmd.com/read/28624220/tat-hafgf14-154-upregulates-adam10-to-attenuate-the-alzheimer-phenotype-of-app-ps1-mice-through-the-pi3k-creb-ire1%C3%AE-xbp1-pathway
#12
Tian Meng, Qin Cao, Peng Lei, Ashley I Bush, Qi Xiang, Zhijian Su, Xiang He, Jack T Rogers, Ing-Ming Chiu, Qihao Zhang, Yadong Huang
Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14-154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622521/the-upr-er-sensor-and-coordinator-of-organismal-homeostasis
#13
REVIEW
Ashley E Frakes, Andrew Dillin
Life is stressful. Organisms are repeatedly exposed to stressors that disrupt protein homeostasis (proteostasis), resulting in protein misfolding and aggregation. To sense and respond to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPR(ER)). However, UPR(ER) function is impaired with age, which, we propose, creates a permissive environment for protein aggregation, unresolved ER stress, and chronic inflammation...
June 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28622510/microbial-genetic-composition-tunes-host-longevity
#14
Bing Han, Priya Sivaramakrishnan, Chih-Chun J Lin, Isaiah A A Neve, Jingquan He, Li Wei Rachel Tay, Jessica N Sowa, Antons Sizovs, Guangwei Du, Jin Wang, Christophe Herman, Meng C Wang
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPR(mt)) in the host...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622297/p53-mediated-suppression-of-bip-triggers-bik-induced-apoptosis-during-prolonged-endoplasmic-reticulum-stress
#15
Ignacio López, Anne-Sophie Tournillon, Rodrigo Prado Martins, Konstantinos Karakostis, Laurence Malbert-Colas, Karin Nylander, Robin Fåhraeus
Physiological and pathological conditions that affect the folding capacity of the endoplasmic reticulum (ER) provoke ER stress and trigger the unfolded protein response (UPR). The UPR aims to either restore the balance between newly synthesized and misfolded proteins or if the damage is severe, to trigger cell death. However, the molecular events underlying the switch between repair and cell death are not well understood. The ER-resident chaperone BiP governs the UPR by sensing misfolded proteins and thereby releasing and activating the three mediators of the UPR: PERK, IRE1 and ATF6...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28622296/bcl-2-family-integrating-stress-responses-at-the-er-to-control-cell-demise
#16
REVIEW
Philippe Pihán, Amado Carreras-Sureda, Claudio Hetz
In the last decade, the endoplasmic reticulum (ER) has emerged as a central organelle regulating the core mitochondrial apoptosis pathway. At the ER membrane, a variety of stress signals are integrated toward determining cell fate, involving a complex cross talk between key homeostatic pathways including the unfolded protein response, autophagy, calcium signaling and mitochondrial bioenergetics. In this context, key regulators of cell death of the BCL-2 and TMBIM/BI-1 family of proteins have relevant functions as stress rheostats mediated by the formation of distinct protein complexes that regulate the switch between adaptive and proapoptotic phases under stress...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28620171/mechanical-stability-of-talin-rod-controls-cell-migration-and-substrate-sensing
#17
Rolle Rahikainen, Magdaléna von Essen, Markus Schaefer, Lei Qi, Latifeh Azizi, Conor Kelly, Teemu O Ihalainen, Bernhard Wehrle-Haller, Martin Bastmeyer, Cai Huang, Vesa P Hytönen
Cells adhere to the surrounding tissue and probe its mechanical properties by forming cell-matrix adhesions. Talin is a critical adhesion protein and participates in the transmission of mechanical signals between extracellular matrix and cell cytoskeleton. Force induced unfolding of talin rod subdomains has been proposed to act as a cellular mechanosensor, but so far evidence linking their mechanical stability and cellular response has been lacking. Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and results in the formation of talin-rich but unstable adhesions...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620018/correction-for-papa-and-germain-sirt3-regulates-a-novel-arm-of-the-mitochondrial-unfolded-protein-response
#18
Luena Papa, Doris Germain
No abstract text is available yet for this article.
July 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28619709/loss-of-fam46c-promotes-cell-survival-in-myeloma
#19
Yuan Xiao Zhu, Chang-Xin Shi, Laura A Bruins, Patrick Jedlowski, Xuewei Wang, K Martin Kortüm, Moulun Luo, Jonathan Ahmann, Esteban Braggio, A Keith Stewart
FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis has not been determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response (UPR) pathway and induced mitochondrial dysfunction...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28619261/sequestosome-1-sqstm1-p62-maintains-protein-folding-capacity-under-endoplasmic-reticulum-stress-in-mouse-hypothalamic-organotypic-culture
#20
Takashi Tominaga, Motomitsu Goto, Takeshi Onoue, Akira Mizoguchi, Mariko Sugiyama, Taku Tsunekawa, Daisuke Hagiwara, Yoshiaki Morishita, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima
Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study...
June 12, 2017: Neuroscience Letters
keyword
keyword
30089
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"