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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/28634818/sg2na-is-a-regulator-of-endoplasmic-reticulum-er-homeostasis-as-its-depletion-leads-to-er-stress
#2
Buddhi Prakash Jain, Shweta Pandey, Nikhat Saleem, Goutam K Tanti, Shalini Mishra, Shyamal K Goswami
SG2NA belongs to a three-member striatin subfamily of WD40 repeat superfamily of proteins. It has multiple protein-protein interaction domains involved in assembling supramolecular signaling complexes. Earlier, we had demonstrated that there are at least five variants of SG2NA generated by alternative splicing, intron retention, and RNA editing. Such versatile and dynamic mode of regulation implicates it in tissue development. In order to shed light on its role in cell physiology, total proteome analysis was performed in NIH3T3 cells depleted of 78 kDa SG2NA, the only isoform expressing therein...
June 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28634653/assessing-the-combined-toxicity-of-bmaa-and-its-isomers-2-4-dab-and-aeg-in-vitro-using-human-neuroblastoma-cells
#3
Brendan J Main, Kenneth J Rodgers
The non-protein amino acid (NPAA) ß-methylamino-L-alanine (BMAA) is produced by a diverse range of cyanobacteria, diatoms and dinoflagellates, and is present in both aquatic and terrestrial ecosystems globally. Exposure to BMAA has been implicated in the development of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). BMAA is often found in nature along with its structural isomers 2,4-diaminobutyric acid (2,4-DAB) and aminoethylglycine (AEG); however, the toxicity of these NPAAs in combination has not been examined...
June 20, 2017: Neurotoxicity Research
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
#4
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/28632169/the-novel-mechanisms-concerning-the-inhibitions-of-palmitate-induced-proinflammatory-factor-releases-and-endogenous-cellular-stress-with-astaxanthin-on-min6-%C3%AE-cells
#5
Atsuko Kitahara, Kazuto Takahashi, Naru Morita, Toshitaka Murashima, Hirohisa Onuma, Yoshikazu Sumitani, Toshiaki Tanaka, Takuma Kondo, Toshio Hosaka, Hitoshi Ishida
Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of pro-inflammatory adipokines monocyte chemoattractant protein-1 (MCP-1) and VEGF120 (vascular endothelial growth factor). We therefore investigated the influence of astaxanthin on palmitate-stimulated MCP-1 and VEGF120 secretion in mouse insulinoma (MIN6) pancreatic β-cells...
June 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28631572/endoplasmic-reticulum-stress-could-induce-autophagy-and-apoptosis-and-enhance-chemotherapy-sensitivity-in-human-esophageal-cancer-ec9706-cells-by-mediating-pi3k-akt-mtor-signaling-pathway
#6
Fang Zhou, Yan-Hua Li, Jian-Jun Wang, Jia Pan, Hong Lu
The study was designed to explore the mechanism of tunicamycin-induced endoplasmic reticulum stress in human esophageal cancer EC9706 cells and EC109 cells, as well as its effects on cell autophagy, apoptosis, and chemoresistance. Tunicamycin-induced endoplasmic reticulum stress model was established in EC9706 and EC109 cell lines. Western blotting was employed to detect the expression of endoplasmic reticulum stress iconic protein GRP78. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the effect of different cisplatin and tunicamycin concentrations on survival rate of EC9706 cells and EC109 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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
#7
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/28630914/deregulated-ca-2-cycling-underlies-the-development-of-arrhythmia-and-heart-disease-due-to-mutant-obscurin
#8
Li-Yen R Hu, Maegen A Ackermann, Peter A Hecker, Benjamin L Prosser, Brendan King, Kelly A O'Connell, Alyssa Grogan, Logan C Meyer, Christopher E Berndsen, Nathan T Wright, W Jonathan Lederer, Aikaterini Kontrogianni-Konstantopoulos
Obscurins are cytoskeletal proteins with structural and regulatory roles encoded by OBSCN. Mutations in OBSCN are associated with the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Specifically, the R4344Q mutation present in immunoglobulin domain 58 (Ig58) was the first to be linked with the development of HCM. To assess the effects of R4344Q in vivo, we generated the respective knock-in mouse model. Mutant obscurins are expressed and incorporated normally into sarcomeres...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630659/homocysteine-induces-apoptosis-of-human-umbilical-vein-endothelial-cells-via-mitochondrial-dysfunction-and-endoplasmic-reticulum-stress
#9
Zhimin Zhang, Congying Wei, Yanfen Zhou, Tao Yan, Zhengqiang Wang, Wei Li, Lianyou Zhao
Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28630491/chronic-high-fat-feeding-restricts-islet-mrna-translation-initiation-independently-of-er-stress-via-dna-damage-and-p53-activation
#10
Masayuki Hatanaka, Emily Anderson-Baucum, Alexander Lakhter, Tatsuyoshi Kono, Bernhard Maier, Sarah A Tersey, Yukio Tanizawa, Carmella Evans-Molina, Raghavendra G Mirmira, Emily K Sims
Under conditions of high fat diet (HFD) consumption, glucose dyshomeostasis develops when β-cells are unable to adapt to peripheral insulin demands. Few studies have interrogated the molecular mechanisms of β-cell dysfunction at the level of mRNA translation under such conditions. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed clear trends toward global reductions in mRNA translation with a significant reduction in the polyribosome/monoribosome ratio for Pdx1 mRNA...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630460/oxidative-and-endoplasmic-reticulum-stress-is-impaired-in-leukocytes-from-metabolically-unhealthy-vs-healthy-obese-individuals
#11
C Bañuls, S Rovira-Llopis, S Lopez-Domenech, N Diaz-Morales, A Blas-Garcia, S Veses, C Morillas, V M Victor, M Rocha, A Hernandez-Mijares
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO), and 31 had type 2 diabetes (MADO)...
June 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28630146/er-stress-causes-widespread-protein-aggregation-and-prion-formation
#12
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/28629580/folding-underlies-bidirectional-role-of-gpr37-pael-r-in-parkinson-disease
#13
REVIEW
Lina Leinartaité, Per Svenningsson
Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent role, particularly in relation to Parkinson disease (PD). GPR37 is a substrate for parkin and accumulates abnormally in autosomal recessive juvenile parkinsonism, contributing to endoplasmic reticulum stress and death of dopaminergic neurons...
June 16, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28628644/targeting-multiple-pro-apoptotic-signaling-pathways-with-curcumin-in-prostate-cancer-cells
#14
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/28628039/chrebp-refines-the-hepatic-response-to-fructose-to-protect-the-liver-from-injury
#15
Angela M Hall, Brian N Finck
Overconsumption of fructose and other sugars has been linked to nonalcoholic fatty liver disease (NAFLD); however, the sugar-associated effects that lead to disease are poorly defined. In this issue of the JCI, Zhang and colleagues show that the carbohydrate response element-binding protein (ChREBP) coordinates an adaptive response to a high-fructose diet in mice and that loss of this transcription factor leads to hepatic inflammation and early signs of fibrosis. Intriguingly, ChREBP-dependent effects were due to an exaggerated activation of the proapoptotic arms of the endoplasmic reticulum stress response that is probably secondary to inappropriate derepression of cholesterol biosynthesis...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627778/engineering-cho-cells-with-an-oncogenic-kit-improves-cells-growth-resilience-to-stress-and-productivity
#16
Mohamed Mahameed, Boaz Tirosh
An optimized biomanufacturing process in mammalian cells is contingent on the ability of the producing cells to reach high viable cell densities. In addition, at the peak of growth, cells need to continue producing the biological entity at a consistent quality. Thus, engineering cells with robust growth performance and resilience to variable stress conditions is highly desirable. The tyrosine kinase receptor, KIT, plays a key role in cell differentiation and the survival of several immune cell types. Its oncogenic mutant, D816V, endows cells with high proliferation capacity and resistance to kinase inhibitors...
June 19, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28627684/beneficial-effects-of-huaiqihuang-on-hyperglycemia-induced-mpc5-podocyte-dysfunction-through-the-suppression-of-mitochondrial-dysfunction-and-endoplasmic-reticulum-stress
#17
Ting-Xia Li, Jian-Hua Mao, Lei Huang, Hai-Dong Fu, Shuo-Hui Chen, Ai-Min Liu, Yu-Qin Liang
The present study was performed to investigate the effect of Huaiqihuang (HQH) on hyperglycemia (HG)-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress in MPC5 podocytes. The effects of HQH and HG on cell viability were assessed using an MTT assay. mRNA and protein expression levels were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, whereas reactive oxygen species production and alterations in mitochondrial membrane potential were assessed using flow cytometry...
June 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627612/targeted-inhibition-of-endoplasmic-reticulum-stress-new-hope-for-renal-fibrosis-review
#18
Ben Ke, Na Zhu, Fuli Luo, Yang Xu, Xiangdong Fang
Chronic kidney disease (CKD) has a very high mortality rate and remains a global health challenge. Inhibiting renal fibrosis is one of the most promising therapeutic strategies for CKD. Recent studies have indicated that endoplasmic reticulum stress (ERS) serves an active role in the development of acute and chronic kidney disease, especially with regards to renal fibrosis. In the current review, the authors summarize the latest understanding of the role of ERS during the onset of renal fibrosis. ERS promotes renal fibrosis through multiple signaling pathways, such as transforming growth factor‑β, epithelial‑mesenchymal transition and oxidative stress...
June 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#19
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
#20
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
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