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https://www.readbyqxmd.com/read/29221916/dna-methylation-signatures-at-endoplasmic-reticulum-stress-genes-are-associated-with-adiposity-and-insulin-resistance
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28754881/sp110-enhances-macrophage-resistance-to-mycobacterium-tuberculosis-via-inducing-endoplasmic-reticulum-stress-and-inhibiting-anti-apoptotic-factors
#14
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...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754848/microrna-199a-acts-as-a-potential-suppressor-of-cardiomyocyte-autophagy-through-targeting-hspa5
#15
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)...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28681934/3-4-dihydroxybenzalacetone-and-caffeic-acid-phenethyl-ester-induce-preconditioning-er-stress-and-autophagy-in-sh-sy5y-cells
#16
Ryoichi Tomiyama, Ken Takakura, Shouhei Takatou, Thuong M Le, Takumi Nishiuchi, Yutaka Nakamura, Tetsuya Konishi, Seiichi Matsugo, Osamu Hori
3,4-dihydroxybenzalacetone (DBL) and Caffeic acid phenethyl ester (CAPE) are both catechol-containing phenylpropanoid derivatives with diverse bioactivities. In the present study, we analyzed the ability of these compounds to activate the unfolded protein response (UPR) and the oxidative stress response. When human SH-SY5Y neuroblastoma cells were treated with DBL or CAPE, the expression of endoplasmic reticulum (ER) stress-related genes such as HSPA5, HYOU1, DDIT3, and SEC61b increased to a larger extent in response to CAPE treatment, while that of antioxidant genes such as HMOX1, GCLM, and NQO1 increased to a larger extent in response to DBL treatment...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28679464/linoleic-la-and-linolenic-ala-acid-concentrations-in-follicular-fluid-of-prepubertal-goats-and-their-effect-on-oocyte-in-vitro-maturation-and-embryo-development
#17
Montserrat Roura, María G Catalá, Sandra Soto-Heras, Sondes Hammami, Dolors Izquierdo, Ali Fouladi-Nashta, Maria-Teresa Paramio
In this study we assessed the concentration of linoleic acid (LA) and linolenic acid (ALA) in follicular fluid of prepubertal goats according to follicle size (<3mm or ≥3mm) by gas chromatography and tested the addition of different LA and ALA (LA:ALA) concentration ratios (50:50, 100:50 and 200:50µM) to the IVM medium on embryo development, mitochondrial activity, ATP concentration and relative gene expression (RPL19, ribosomal protein L19; SLC2A1, facilitated glucose transporter 1; ATF4, activating transcription factor 4; GPX1, glutathione peroxidase 1; HSPA5, heat-shock protein family A 70 kDa; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; DNMT1, DNA methyltransferase 1; GCLC, glutamate-cysteine ligase catalytic subunit; SOD1, superoxide dismutase 1)...
July 6, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28668844/the-effect-of-afatinib-treatment-in-non-small-cell-lung-cancer-cells
#18
Joanna Pancewicz-Wojtkiewicz, Pawel Leszek Bernatowicz
BACKGROUND: Non-small cell lung cancer (NSCLC) is a very aggressive and histologically heterogeneous type of lung cancer. The main problem in the treatment of NSCLC is chemoresistance and metastasis. Compared to other malignant tumors, many molecular mechanisms are dysfunctional in NSCLC. Epidermal growth factor receptor (EGFR) is one of the most frequently mutated genes in NSCLC. MATERIALS AND METHODS: We investigated the effect of afatinib the against A549 NSCLC cell line, because it is active against mutated EGFR...
July 2017: Anticancer Research
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 M Ahmann, Esteban Braggio, A Keith Stewart
FAM46C is one of the most recurrently mutated genes in multiple myeloma; however its role in disease pathogenesis has not been determined. Here we demonstrate that wild-type (WT) FAM46C overexpression induces substantial cytotoxicity in multiple myeloma cells. In contrast, FAM46C mutations found in multiple myeloma 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 pathway and induced mitochondrial dysfunction...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28601093/granulin-epithelin-precursor-interacts-with-78-kda-glucose-regulated-protein-in-hepatocellular-carcinoma
#20
Chi Wai Yip, Ching Yan Lam, Terence C W Poon, Tan To Cheung, Phyllis F Y Cheung, Sze Wai Fung, Xiao Qi Wang, Idy C Y Leung, Linda W C Ng, Chung Mau Lo, George S W Tsao, Siu Tim Cheung
BACKGROUND: Granulin-epithelin precursor (GEP) is a secretory growth factor, which has been demonstrated to control cancer growth, invasion, drug resistance and immune escape. Our previous studies and others also demonstrated its potential in targeted therapy. Comprehensive characterization of GEP partner on cancer cells are warranted. We have previously shown that GEP interacted with heparan sulfate on the surface of liver cancer cells and the interaction is crucial for GEP-mediated signaling transduction...
June 10, 2017: BMC Cancer
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