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https://www.readbyqxmd.com/read/29453283/chemical-stresses-fail-to-mimic-the-unfolded-protein-response-resulting-from-luminal-load-with-unfolded-polypeptides
#1
Timothy J Bergmann, Ilaria Fregno, Fiorenza Fumagalli, Andrea Rinaldi, Francesco Bertoni, Paul J Boersema, Paola Picotti, Maurizio Molinari
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29408669/effect-of-diesel-exhaust-generated-by-a-city-bus-engine-on-stress-responses-and-innate-immunity-in-primary-bronchial-epithelial-cell-cultures
#2
M C Zarcone, E Duistermaat, M J Alblas, A van Schadewijk, D K Ninaber, V Clarijs, M M Moerman, D Vaessen, P S Hiemstra, I M Kooter
Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic. We studied the cellular response of primary bronchial epithelial cells (PBECs) at the air-liquid interface (ALI) to the exposure to whole diesel exhaust (DE) generated by a Euro V bus engine, followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi) bacteria to mimic microbial exposure...
February 8, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29407824/developmental-toxicity-induced-by-pm2-5-through-endoplasmic-reticulum-stress-and-autophagy-pathway-in-zebrafish-embryos
#3
Yun Zhang, Saiyu Li, Juanjuan Li, Liwen Han, Qiuxia He, Rongchun Wang, Ximin Wang, Kechun Liu
The aims of this study were to investigate the mechanism underlying the developmental toxicity of fine particulate matter (PM2.5) and provide a more thorough understanding of the toxicity of PM2.5 in an ecological environment. Zebrafish embryos at 4 h post-fertilization were exposed to PM2.5 at doses of 200, 300, 400, 500, 600 and 800 μg/mL for 120 h. The mortality, hatching rate, morphology score, body length, locomotor capacity, histological changes, antioxidant defense system, leukocyte migration, inflammation-related gene mRNA expression, endoplasmic reticulum stress (ERS) and autophagy were evaluated to study PM2...
January 25, 2018: Chemosphere
https://www.readbyqxmd.com/read/29386544/identification-of-molecular-pathways-and-candidate-genes-associated-with-cocks-comb-size-trait-by-genome-wide-transcriptome-analysis
#4
Yifan Liu, Yunjie Tu, Ming Zhang, Gaige Ji, Kun Wang, Yanju Shan, Xiaojun Ju, Di Zhang, Jingting Shu, Jianmin Zou
The comb of the male is an important secondary sexual characteristic. Although quantitative trait loci (QTLs) related to comb size have been identified, molecular mechanisms underlying this trait remain mostly unknown. In this study, RNA sequencing (RNA-seq) was employed to compare whole transcriptomic differences between two groups of Partridge Shank chickens that are divergent in comb sizes. A total of 563 differentially expressed genes (DEGs) were identified, including 277 up-regulated and 286 down-regulated DEGs...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328656/design-and-synthesis-of-novel-reactive-oxygen-species-inducers-for-the-treatment-of-pancreatic-ductal-adenocarcinoma
#5
Yuting Kuang, Mario Sechi, Salvatore Nurra, Mats Ljungman, Nouri Neamati
Altering redox homeostasis provides distinctive therapeutic opportunities for the treatment of pancreatic cancer. Quinazolinediones (QDs) are novel redox modulators that we previously showed to induce potent growth inhibition in pancreatic ductal adenocarcinoma (PDAC) cell lines. Our lead optimization campaign yielded QD325 as the most potent redox modulator candidate inducing substantial reactive oxygen species (ROS) in PDAC cells. Nascent RNA sequencing following treatments with the QD compounds revealed induction of stress responses in nucleus, endoplasmic reticulum, and mitochondria of pancreatic cancer cells...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29261001/regulation-of-autophagic-proteolysis-by-the-n-recognin-sqstm1-p62-of-the-n-end-rule-pathway
#6
Hyunjoo Cha-Molstad, Su Hyun Lee, Jung Gi Kim, Ki Woon Sung, Joonsung Hwang, Sang Mi Shim, Srinivasrao Ganipisetti, Terry McGuire, Inhee Mook-Jung, Aaron Ciechanover, Xiang-Qun Xie, Bo Yeon Kim, Yong Tae Kwon
In macroautophagy/autophagy, cargoes are collected by specific receptors, such as SQSTM1/p62 (sequestosome 1), and delivered to phagophores for lysosomal degradation. To date, little is known about how cells modulate SQSTM1 activity and autophagosome biogenesis in response to accumulating cargoes. In this study, we show that SQSTM1 is an N-recognin whose ZZ domain binds N-terminal arginine (Nt-Arg) and other N-degrons (Nt-Lys, Nt-His, Nt-Trp, Nt-Phe, and Nt-Tyr) of the N-end rule pathway. The substrates of SQSTM1 include the endoplasmic reticulum (ER)-residing chaperone HSPA5/GRP78/BiP...
December 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29260979/hspa5-negatively-regulates-lysosomal-activity-through-ubiquitination-of-mul1-in-head-and-neck-cancer
#7
Sun-Yong Kim, Hyo Jeong Kim, Haeng-Jun Kim, Dae Ho Kim, Chul-Ho Kim, Jae Ho Han, Hyung Kwon Byeon, Keunho Lee
HSPA5/GRP78/BiP plays an important role in cell survival or tumor progression. For these reasons, HSPA5 is an emerging therapeutic target in cancer development. Here we report that HSPA5 contributes to head and neck cancer (HNC) survival via maintenance of lysosomal activity; however, a nonthermal plasma (NTP, considered as a next-generation cancer therapy)-treated solution (NTS) inhibits HNC progression through HSPA5-dependent alteration of lysosomal activity. HSPA5 prevents NTS-induced lysosome inhibition through lysosomal-related proteins or regulation of gene expression...
December 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29221916/dna-methylation-signatures-at-endoplasmic-reticulum-stress-genes-are-associated-with-adiposity-and-insulin-resistance
#8
Omar Ramos-Lopez, Jose I Riezu-Boj, Fermin I Milagro, J Alfredo Martinez
A sustained activation of the unfolded protein response and the subsequent endoplasmic reticulum (ER) stress has been involved in the onset and severity of several metabolic diseases. The aim of this study was to analyze the association of DNA methylation signatures at ER stress genes with adiposity traits and related metabolic disorders. An epigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in an adult population (n=474). DNA methylation status in peripheral white blood cells was analyzed by a microarray approach...
November 28, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29198452/betaglycan-tgfbr3-up-regulation-correlates-with-increased-tgf-%C3%AE-signaling-in-marfan-patient-fibroblasts-in-vitro
#9
Menno Evert Groeneveld, Natalija Bogunovic, René John Philip Musters, Geert Jan Tangelder, Gerard Pals, Willem Wisselink, Dimitra Micha, Kak Khee Yeung
BACKGROUND: Marfan syndrome (MFS), a congenital connective tissue disorder leading to aortic aneurysm development, is caused by fibrillin-1 (FBN1) gene mutations. Transforming growth factor beta (TGF-β) might play a role in the pathogenesis. It is still a matter of discussion if and how TGF-β up-regulates the intracellular downstream pathway, although TGF-β receptor 3 (TGFBR3 or Betaglycan) is thought to be involved. We aimed to elucidate the role of TGFBR3 protein in TGF-β signaling in Marfan patients...
November 4, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29187900/the-cytotoxic-effects-of-dimethyl-sulfoxide-in-mouse-preimplantation-embryos-a-mechanistic-study
#10
Min-Hee Kang, Joydeep Das, Sangiliyandi Gurunathan, Hwan-Woo Park, Hyuk Song, Chankyu Park, Jin-Hoi Kim
Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, a vehicle for drug therapy, and a cryoprotectant for cultured cells. DMSO induced embryonic defects and its mechanism of action remains unclear. The rationale is based on the assumption that DMSO supplementation should induce long-term negative effects on both pre- and post-implantation embryo development. Methods: DMSO induced oxidative stress, ER stress, autophagy, mitophagy, signaling responsible genes and proteins were determined by RT-qPCR, Western blotting, immunofluorescence, and confocal microscopy...
2017: Theranostics
https://www.readbyqxmd.com/read/29163679/identification-of-molecular-mechanisms-of-glutamine-in-pancreatic-cancer
#11
Zhen-Yi Jia, Tong-Yi Shen, Wei Jiang, Huan-Long Qin
The aim of the present study was to explore the critical genes and molecular mechanisms in pancreatic cancer (PC) cells with glutamine. By analyzing microarray data GSE17632 from the Gene Expression Omnibus database, the DEGs between PC cells treated with glutamine and without glutamine were evaluated. Additionally, function enrichment analyses and protein-protein interaction (PPI) network construction of DEGs were performed. Network module and literature mining analyses were performed to analyze the critical DEGs in PC cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142990/the-chemical-chaperone-pba-reduces-er-stress-and-autophagy-and-increases-collagen-iv-%C3%AE-5-expression-in-cultured-fibroblasts-from-men-with-x-linked-alport-syndrome-and-missense-mutations
#12
Dongmao Wang, Mardhiah Mohammad, Yanyan Wang, Rachel Tan, Lydia S Murray, Sharon Ricardo, Hayat Dagher, Tom van Agtmael, Judy Savige
Introduction: X-linked Alport syndrome (OMIM 301050) is caused by COL4A5 missense variants in 40% of families. This study examined the effects of chemical chaperone treatment (sodium 4-phenylbutyrate) on fibroblast cell lines derived from men with missense mutations. Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29048640/dal-1-attenuates-epithelial-to-mesenchymal-transition-and-metastasis-by-suppressing-hspa5-expression-in-non-small-cell-lung-cancer
#13
Xiaoliu Qiu, Xiaoying Guan, Wanxia Liu, Yajie Zhang
Metastasis is the primary cause of death in lung cancer patients and EMT (epithelial-mesenchymal transition) promotes metastasis. Previous study revealed that DAL-1 (differentially expressed in adenocarcinoma of the lung) could attenuate EMT and metastasis in non-small cell lung cancer (NSCLC). Further study proved that HSPA5 (heat shock protein 5), which has a promoting effect on EMT, could bind to DAL-1. In this study, the mRNA and protein expression levels of target molecules were detected by RTq-PCR and western blot assays, the migration and invasion abilities were examined by Transwell migration and invasion assay, and the proliferation ability was measured by CCK-8 assay...
September 26, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29042970/effects-of-17-dmag-on-diffuse-large-b-cell-lymphoma-cell-apoptosis
#14
Jia-Jia Li, Jing-Jing Zhang, Xiu Wang, Zi-Min Sun
17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) is a water soluble, semisynthetic derivative of endotoxin that has anticancer effects. The aim of the present study was to determine whether 17-DMAG enhances the apoptosis of lymphoma cells in diffuse large B-cell lymphoma. Apoptosis was induced in SU-DHL-4 diffuse large B-cell lymphoma cells treated with 17-DMAG, as evaluated by MTT assay and flow cytometry analysis. Apoptosis-associated protein levels were assessed using western blotting, and the results indicated that B-cell lymphoma 2 (Bcl-2)-associated protein X (Bax) was upregulated, whereas heat shock protein family A member 5 (HSPA5) and Bcl-2 were downregulated...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28991167/achiral-mannich-base-curcumin-analogs-induce-unfolded-protein-response-and-mitochondrial-membrane-depolarization-in-panc-1-cells
#15
Gábor J Szebeni, Árpád Balázs, Ildikó Madarász, Gábor Pócz, Ferhan Ayaydin, Iván Kanizsai, Roberta Fajka-Boja, Róbert Alföldi, László Hackler, László G Puskás
Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells...
October 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28969051/sp110-enhances-macrophage-resistance-to-mycobacterium-tuberculosis-via-inducing-endoplasmic-reticulum-stress-and-inhibiting-anti-apoptotic-factors
#16
Yongyan Wu, Zekun Guo, Fayang Liu, Kezhen Yao, Mingqing Gao, Yan Luo, Yong Zhang
Tuberculosis remains a leading health problem worldwide and still accounts for about 1.3 million deaths annually. Expression of the mouse Sp110 nuclear body protein (Sp110) upregulates the apoptotic pathway, which plays an essential role in enhancing host immunity to Mycobacterium tuberculosis (Mtb). However, the mechanism of this upregulation is unclear. Here, we have identified 253 proteins in mouse macrophages that interact with Sp110, of which 251 proteins were previously uncharacterized. The results showed that Sp110 interacts with heat shock protein 5 (Hspa5) to activate endoplasmic reticulum (ER) stress-induced apoptosis, and that this is essential for Sp110 enhanced macrophage resistance to Mtb...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969032/microrna-199a-acts-as-a-potential-suppressor-of-cardiomyocyte-autophagy-through-targeting-hspa5
#17
Liang Chen, Fei-Yu Wang, Zhen-Yu Zeng, Ling Cui, Jian Shen, Xiao-Wei Song, Pan Li, Xian-Xian Zhao, Yong-Wen Qin
Autophagy is an adaptive response to cardiomyocytes survival under stress conditions. MicroRNAs (miRNAs, miR) have been described to act as potent modulators of autophagy. To investigate whether and how miR-199a modulated autophagy in vitro, primary cardiomyocytes were treated under starvation to induce autophagy. Results showed that down-regulation of miR-199a was sufficient to activate cardiomyocytes autophagy. MiR-199a suppressed cardiomyocytes autophagy through direct inhibiting heat shock protein family A member 5 (Hspa5)...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912266/lysine-trimethylation-regulates-78-kda-glucose-regulated-protein-proteostasis-during-endoplasmic-reticulum-stress
#18
Jonas Sieber, Nicolas Wieder, Mauricio Ostrosky-Frid, Moran Dvela-Levitt, Ozan Aygün, Namrata D Udeshi, Steven A Carr, Anna Greka
The upregulation of chaperones such as the 78-kDa glucose-regulated protein (GRP78; also referred to as BiP or HSPA5) is part of the adaptive cellular response to endoplasmic reticulum (ER) stress. GRP78 is widely used as a marker of the unfolded protein response, associated with sustained ER stress. Here, we report the discovery of a proteostatic mechanism involving GRP78 trimethylation in the context of ER stress. Using mass spectrometry-based proteomics, we identified two GRP78 fractions, one homeostatic and one induced by ER stress...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28796263/mir-30c-regulates-cisplatin-induced-apoptosis-of-renal-tubular-epithelial-cells-by-targeting-bnip3l-and-hspa5
#19
Bin Du, Xiao-Meng Dai, Shuang Li, Guo-Long Qi, Guang-Xu Cao, Ying Zhong, Pei-di Yin, Xue-Song Yang
As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28757676/structure-and-function-of-enterocyte-in-intrauterine-growth-retarded-pig-neonates
#20
Karolina Ferenc, Tomasz Pilżys, Tomasz Skrzypek, Damian Garbicz, Michał Marcinkowski, Małgorzata Dylewska, Paweł Gładysz, Oleksandr Skorobogatov, Zdzisław Gajewski, Elżbieta Grzesiuk, Romuald Zabielski
The intestine of intrauterine growth retarded (IUGR) neonates showed different morphology compared to neonates born with normal body weight (NBW). The aim of the present study was to investigate the ultrastructure and proteomic profile of the gut epithelium in IUGR pig neonates with special attention to the digestive and absorptive function. Intestine tissue samples were investigated in 7-day-old IUGR and NBW littermate piglets using histometry, immunofluorescence, scanning electron microscopy (SEM), and mass spectrometry analysis...
2017: Disease Markers
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