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https://www.readbyqxmd.com/read/28098884/renin-angiotensin-system-activation-accelerates-atherosclerosis-in-experimental-renal-failure-by-promoting-endoplasmic-reticulum-stress-related-inflammation
#1
Jia Yang, Xi Zhang, Xinyi Yu, Weixue Tang, Hua Gan
In this study, we investigated the association between the renin-angiotensin system (RAS), endoplasmic reticulum (ER) stress and atherosclerosis (AS) in uremic apolipoprotein E knockout (apoE-/-) mice. Mild uremia was induced by a 5/6 nephrectomy (5/6 Nx) in 10-week-old apoE-/- mice. Four weeks after nephrectomy, the mice received losartan or no treatment for 16 weeks. Sham-operated mice served as the controls. We found that uremia accelerated AS at the aortic root. The activation of ER stress and the significant upregulation of pro-inflammatory cytokines and chemokines were observed in the uremic mice...
January 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28098812/novel-aflatoxin-degrading-enzyme-from-bacillus-shackletonii-l7
#2
Liang Xu, Mohamed Farah Eisa Ahmed, Lancine Sangare, Yueju Zhao, Jonathan Nimal Selvaraj, Fuguo Xing, Yan Wang, Hongping Yang, Yang Liu
Food and feed contamination by aflatoxin (AF)B₁ has adverse economic and health consequences. AFB₁ degradation by microorganisms or microbial enzymes provides a promising preventive measure. To this end, the present study tested 43 bacterial isolates collected from maize, rice, and soil samples for AFB₁-reducing activity. The higher activity was detected in isolate L7, which was identified as Bacillus shackletonii. L7 reduced AFB₁, AFB₂, and AFM₁ levels by 92.1%, 84.1%, and 90.4%, respectively, after 72 h at 37 °C...
January 14, 2017: Toxins
https://www.readbyqxmd.com/read/28098359/m2-like-macrophages-induce-colon-cancer-cell-invasion-via-matrix-metalloproteinases
#3
Katyayni Vinnakota, Yuan Zhang, Benson Chellakkan Selvanesan, Geriolda Topi, Tavga Salim, Janna Sand-Dejmek, Gunilla Jönsson, Anita Sjölander
The inflammatory milieu plays an important role in colon cancer development and progression. Previously, we have shown that tumor-associated macrophages (TAMs), an important component of the tumor microenvironment, are enriched in tumors compared with normal tissue and confer a poorer prognosis. In the present study, we found that matrix metallopeptidase-9 (MMP-9), which degrades extracellular matrix proteins, was increased in biopsies from colon cancer patients and in mouse xenografts with SW480 cell-derived tumors...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28098337/characterisation-of-the-enzymatic-properties-of-mpapr1-an-aspartic-protease-secreted-by-the-wine-yeast-metschnikowia-pulcherrima
#4
Louwrens Wiid Theron, Marina Bely, Benoit Divol
BACKGROUND: MpAPr1, encoding an acid protease from the wine yeast Metschnikowia pulcherrima IWBT Y1123, was previously isolated and shown to display potential activity against casein and grape proteins. However, its characterisation remained partial. RESULTS: MpAPr1 was cloned into the pGAPZαA vector and transformed into Komagataella pastoris X33 for heterologous expression. After verification of activity, the enzyme properties were characterised. Protease activity within the concentrated supernatant was retained over a pH range of 3...
January 18, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28098291/investigation-into-the-bioavailability-of-milk-protein-derived-peptides-with-dipeptidyl-peptidase-iv-inhibitory-activity-using-caco-2-cell-monolayers
#5
Isabelle M E Lacroix, Xiu-Min Chen, David D Kitts, Eunice C Y Li-Chan
In recent years, peptides derived from a variety of dietary proteins have been reported to exhibit inhibitory activity against the dipeptidyl-peptidase IV (DPP-IV) enzyme, a target in the management of type 2 diabetes. While much attention has been given to the production and identification of peptides with DPP-IV inhibitory activity from food proteins, particularly dairy proteins, little is known on the bioavailability of these molecules. In this study, the stability and transport of five previously identified milk-derived peptides (LKPTPEGDL, LPYPY, IPIQY, IPI and WR) and a whey protein isolate (WPI) digest with DPP-IV-inhibitory activity were investigated using Caco-2 cell monolayers as a model system for human intestinal absorption...
January 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28098260/hepatitis-b-virus-x-protein-is-capable-of-down-regulating-protein-level-of-host-antiviral-protein-apobec3g
#6
Ruidong Chen, Xue Zhao, Yongxiang Wang, Youhua Xie, Jing Liu
The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family proteins bind RNA and single-stranded DNA, and create C-to-U base modifications through cytidine deaminase activity. APOBEC3G restricts human immunodeficiency virus 1 (HIV-1) infection by creating hypermutations in proviral DNA, while HIV-1-encoded vif protein antagonizes such restriction by targeting APOBEC3G for degradation. APOBEC3G also inhibits hepatitis B virus (HBV): APOBEC3G co-expression inhibits HBV replication and evidences exist indicating APOBEC3G-mediated HBV hypermutations in patients...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098200/cullin-7-mediates-proteasomal-and-lysosomal-degradations-of-rat-eag1-potassium-channels
#7
Po-Hao Hsu, Yu-Ting Ma, Ya-Ching Fang, Jing-Jia Huang, Yu-Ling Gan, Pei-Tzu Chang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Mammalian Eag1 (Kv10.1) potassium (K(+)) channels are widely expressed in the brain. Several mutations in the gene encoding human Eag1 K(+) channel have been associated with congenital neurodevelopmental anomalies. Currently very little is known about the molecules mediating protein synthesis and degradation of Eag1 channels. Herein we aim to ascertain the protein degradation mechanism of rat Eag1 (rEag1). We identified cullin 7 (Cul7), a member of the cullin-based E3 ubiquitin ligase family, as a novel rEag1 binding partner...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098164/uncovering-the-sumoylation-and-ubiquitylation-crosstalk-in-human-cells-using-sequential-peptide-immunopurification
#8
Frédéric Lamoliatte, Francis P McManus, Ghizlane Maarifi, Mounira K Chelbi-Alix, Pierre Thibault
Crosstalk between the SUMO and ubiquitin pathways has recently been reported. However, no approach currently exists to determine the interrelationship between these modifications. Here, we report an optimized immunoaffinity method that permits the study of both protein ubiquitylation and SUMOylation from a single sample. This method enables the unprecedented identification of 10,388 SUMO sites in HEK293 cells. The sequential use of SUMO and ubiquitin remnant immunoaffinity purification facilitates the dynamic profiling of SUMOylated and ubiquitylated proteins in HEK293 cells treated with the proteasome inhibitor MG132...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#9
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28097745/immature-core-protein-of-hepatitis-c-virus-induces-an-unfolded-protein-response-through-inhibition-of-erad-l-in-a-yeast-model-system
#10
Shota Takahashi, Naoko Sato, Junichi Kikuchi, Hideaki Kakinuma, Jun Okawa, Yukiko Masuyama, Singo Iwasa, Hayato Irokawa, Gi-Wook Hwang, Akira Naganuma, Michinori Kohara, Shusuke Kuge
The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28097724/unphosphorylated-eiia-ntr-induces-clpap-mediated-degradation-of-rpos-in-azotobacter-vinelandii
#11
Luis Felipe Muriel-Millán, Soledad Moreno, Ramsés Gallegos-Monterrosa, Guadalupe Espín
The nitrogen-related phosphotransferase system (PTS(Ntr) ) is composed of the EI(Ntr) , NPr and EIIA(Ntr) proteins that form a phosphorylation cascade from phosphoenolpyruvate. PTS(Ntr) is a global regulatory system present in most Gram-negative bacteria that controls some pivotal processes such as potassium and phosphate homeostasis, virulence, nitrogen fixation and ABC transport activation. In the soil bacterium Azotobacter vinelandii, unphosphorylated EIIA(Ntr) negatively regulates the expression of genes related to the synthesis of the bioplastic polyester poly-β-hydroxybutyrate (PHB) and cyst-specific lipids alkylresorcinols (ARs)...
January 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28097431/placental-dapk1-and-autophagy-marker-lc3b-ii-are-dysregulated-by-tnf-%C3%AE-in-a-gestational-age-dependent-manner
#12
Andreas Prokesch, Astrid Blaschitz, Tamara Bauer, Gerit Moser, Ursula Hiden, Julianna Zadora, Ralf Dechend, Florian Herse, Martin Gauster
Autophagy, a cell-survival process responsible for degradation of protein aggregates and damaged organelles, is increasingly recognized as another mechanism essential for human placentation. A substantial body of experiments suggests inflammation and oxidative stress as the underlying stimuli for altered placental autophagy, giving rise to placenta dysfunction and pregnancy pathologies. Here, the hypothesis is tested whether or not pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α are able to influence the expression profile of autophagy genes in human first-trimester villous placenta...
January 17, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28097232/vps34-regulates-myofibril-proteostasis-to-prevent-hypertrophic-cardiomyopathy
#13
Hirotaka Kimura, Satoshi Eguchi, Junko Sasaki, Keiji Kuba, Hiroki Nakanishi, Shunsuke Takasuga, Masakazu Yamazaki, Akiteru Goto, Hiroyuki Watanabe, Hiroshi Itoh, Yumiko Imai, Akira Suzuki, Noboru Mizushima, Takehiko Sasaki
Hypertrophic cardiomyopathy (HCM) is a common heart disease with a prevalence of 1 in 500 in the general population. Several mutations in genes encoding cardiac proteins have been found in HCM patients, but these changes do not predict occurrence or prognosis and the molecular mechanisms underlying HCM remain largely elusive. Here we show that cardiac expression of vacuolar protein sorting 34 (Vps34) is reduced in a subset of HCM patients. In a mouse model, muscle-specific loss of Vps34 led to HCM-like manifestations and sudden death...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28097090/a-comparative-study-of-the-degradation-of-yeast-cyclins-cln1-and-cln2
#14
Inma Quilis, J Carlos Igual
The yeast cyclins Cln1 and Cln2 are very similar in both sequence and function, but some differences in their functionality and localization have been recently described. The control of Cln1 and Cln2 cellular levels is crucial for proper cell cycle initiation. In this work, we analyzed the degradation patterns of Cln1 and Cln2 in order to further investigate the possible differences between them. Both cyclins show the same half-life but, while Cln2 degradation depends on ubiquitin ligases SCF(G)(rr1) and SCF(C)(dc4), Cln1 is affected only by SCF(G)(rr1)...
January 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28096488/novel-superspreader-bacteriophages-promote-horizontal-gene-transfer-by-transformation
#15
Eric C Keen, Valery V Bliskovsky, Francisco Malagon, James D Baker, Jeffrey S Prince, James S Klaus, Sankar L Adhya
: Bacteriophages infect an estimated 10(23) to 10(25) bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub "superspreaders," releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096487/a-clostridium-difficile-specific-gel-forming-protein-required-for-optimal-spore-germination
#16
M Lauren Donnelly, William Li, Yong-Qing Li, Lauren Hinkel, Peter Setlow, Aimee Shen
: Clostridium difficile is a Gram-positive spore-forming obligate anaerobe that is a leading cause of antibiotic-associated diarrhea worldwide. In order for C. difficile to initiate infection, its aerotolerant spore form must germinate in the gut of mammalian hosts. While almost all spore-forming organisms use transmembrane germinant receptors to trigger germination, C. difficile uses the pseudoprotease CspC to sense bile salt germinants. CspC activates the related subtilisin-like protease CspB, which then proteolytically activates the cortex hydrolase SleC...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#17
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096463/deneddylase1-counters-automodification-of-neddylating-enzymes-to-maintain-nedd8-homeostasis-in-arabidopsis
#18
Julia Mergner, Bernhard Kuster, Claus Schwechheimer
In eukaryotes, the conjugation of the ubiquitin-like protein NEDD8 onto protein targets is an important post-translational modification. The best understood neddylation targets are the cullins, scaffold subunits of E3 ubiquitin ligases, where neddylation as well as deneddylation, facilitated by the protease activity of the CSN (COP9 signalosome), are required to control ubiquitin ligase assembly, function and ultimately substrate degradation. Little is known about the role of other deneddylating enzymes besides CSN and the role of neddylation and deneddylation of their substrates...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096448/loss-of-function-mutations-in-hspr-rescue-the-growth-defect-of-a-mycobacterium-tuberculosis-proteasome-activator-e-pafe-mutant
#19
Jordan B Jastrab, Marie I Samanovic, Richard Copin, Bo Shopsin, K Heran Darwin
: Mycobacterium tuberculosis uses a proteasome to degrade proteins by both ATP-dependent and -independent pathways. While much has been learned about ATP-dependent degradation, relatively little is understood about the ATP-independent pathway, which is controlled by Mycobacterium tuberculosis proteasome accessory factor E (PafE). Recently, we found that a Mycobacterium tuberculosis pafE mutant has slowed growth in vitro and is sensitive to killing by heat stress. However, we did not know if these phenotypes were caused by an inability to degrade the PafE-proteasome substrate HspR (heat shock protein repressor), an inability to degrade any damaged or misfolded proteins, or a defect in another protein quality control pathway...
January 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28096371/cox2-mpges1-pge2-pathway-regulates-pd-l1-expression-in-tumor-associated-macrophages-and-myeloid-derived-suppressor-cells
#20
Victor Prima, Lyudmila N Kaliberova, Sergey Kaliberov, David T Curiel, Sergei Kusmartsev
In recent years, it has been established that programmed cell death protein ligand 1 (PD-L1)-mediated inhibition of activated PD-1(+) T lymphocytes plays a major role in tumor escape from immune system during cancer progression. Lately, the anti-PD-L1 and -PD-1 immune therapies have become an important tool for treatment of advanced human cancers, including bladder cancer. However, the underlying mechanisms of PD-L1 expression in cancer are not fully understood. We found that coculture of murine bone marrow cells with bladder tumor cells promoted strong expression of PD-L1 in bone marrow-derived myeloid cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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