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https://www.readbyqxmd.com/read/28927269/discovery-of-tamoxifen-and-n-desmethyl-tamoxifen-protein-targets-in-mcf-7-cells-using-large-scale-protein-folding-and-stability-measurements
#1
Ryenne N Ogburn, Lorrain Jin, He Meng, Michael C Fitzgerald
The proteins in an MCF-7 cell line were probed for tamoxifen (TAM) and n-desmethyl tamoxifen (NDT) induced stability changes using the Stability of Proteins from Rates of Oxidation (SPROX) technique in combination with two different quantitative proteomics strategies, including one based on SILAC and one based on isobaric mass tags. Over 1000 proteins were assayed for TAM- and NDT- induced protein stability changes, and a total of 163 and 200 protein hits were identified in the TAM and NDT studies, respectively...
September 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28926063/methylglyoxal-attenuates-insulin-signaling-and-downregulates-the-enzymes-involved-in-cholesterol-biosynthesis
#2
Arati B Deshmukh, Shakuntala Bai, Aarthy T, Rubina S Kazi, Reema Banarjee, Rajeshwari Rathore, Vijayakumar Mv, Thulasiram Hv, Manoj Kumar Bhat, Kulkarni Mj
Methylglyoxal (MG) is a highly reactive dicarbonyl known to be elevated under the hyperglycemic conditions of diabetes and is implicated in the development of diabetic complications. Therefore, the current study investigates the role of MG in exacerbating insulin resistance at the insulin signaling level, as well as its effect on the global proteomic level. By using insulin sensitive rat muscle cells (L6) and Chinese hamster ovary (CHO) cells stably expressing the insulin receptor (IR) and a glucose transporter fused with green fluorescent protein (GLUT4-GFP), we have observed that MG impairs insulin signaling, inhibits GLUT4 translocation and reduces glucose uptake...
September 19, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28924605/pai-1-is-a-critical-regulator-of-fgf23-homeostasis
#3
Mesut Eren, Aaron T Place, Paul M Thomas, Panagiotis Flevaris, Toshio Miyata, Douglas E Vaughan
Elevated levels of fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, are associated with a number of pathologic conditions including chronic kidney disease, cardiac hypertrophy, and congestive heart failure. Currently, there are no specific treatments available to lower plasma FGF23 levels. We have recently reported that genetic plasminogen activator inhibitor-1 (PAI-1) deficiency provided a significant reduction in circulating FGF23 levels while simultaneously prolonging the life span of Klotho-deficient mice...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28924169/the-clpxp-protease-is-dispensable-for-degradation-of-unfolded-proteins-in-staphylococcus-aureus
#4
Steen G Stahlhut, Abdulelah A Alqarzaee, Camilla Jensen, Niclas S Fisker, Ana R Pereira, Mariana G Pinho, Vinai Chittezham Thomas, Dorte Frees
In living cells intracellular proteolysis is crucial for protein homeostasis, and ClpP proteases are conserved between eubacteria and the organelles of eukaryotic cells. In Staphylococcus aureus, ClpP associates to the substrate specificity factors, ClpX and ClpC forming two ClpP proteases, ClpXP and ClpCP. To address how individual ClpP proteases impact cell physiology, we constructed a S. aureus mutant expressing ClpX with an I265E substitution in the ClpP recognition tripeptide of ClpX. This mutant cannot degrade established ClpXP substrates confirming that the introduced amino acid substitution abolishes ClpXP activity...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923951/bpm-cul3-e3-ligase-modulates-thermotolerance-by-facilitating-negative-regulatory-domain-mediated-degradation-of-dreb2a-in-arabidopsis
#5
Kyoko Morimoto, Naohiko Ohama, Satoshi Kidokoro, Junya Mizoi, Fuminori Takahashi, Daisuke Todaka, Junro Mogami, Hikaru Sato, Feng Qin, June-Sik Kim, Yoichiro Fukao, Masayuki Fujiwara, Kazuo Shinozaki, Kazuko Yamaguchi-Shinozaki
DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN 2A (DREB2A) acts as a key transcription factor in both drought and heat stress tolerance in Arabidopsis and induces the expression of many drought- and heat stress-inducible genes. Although DREB2A expression itself is induced by stress, the posttranslational regulation of DREB2A, including protein stabilization, is required for its transcriptional activity. The deletion of a 30-aa central region of DREB2A known as the negative regulatory domain (NRD) transforms DREB2A into a stable and constitutively active form referred to as DREB2A CA...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923470/tripodal-lipoprotein-variants-with-c-terminal-hydrophobic-residues-allosterically-modulate-activity-of-the-degp-protease
#6
Hyojin Park, Yurie T Kim, Chulwon Choi, Seokhee Kim
DegP, a member of the highly conserved HtrA family of proteases, performs a regulated proteolysis of toxic misfolded proteins in the periplasm of Gram-negative bacteria. The allosteric switch between inactive and active conformations is a central mechanism to carefully control proteolytic activity of DegP and to maintain the optimal cellular fitness, but few other molecules than substrates are known to allosterically control DegP activity. Here, we demonstrate that a mutant variant of an outer membrane lipoprotein, Lpp(+Leu), can function as a novel allosteric effector that changes the dynamic range of DegP activity...
September 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28923245/a20-inhibits-both-the-degradation-and-limited-processing-of-the-nf-%C3%AE%C2%BAb-p105-precursor-a-novel-additional-layer-to-its-regulator-role
#7
Dana Lapid, Shirly Lahav-Baratz, Shai Cohen
p105 plays dual roles in NF-κB signaling: it generates the active subunit p50 and in its precursor form inhibits NF-κB activation. p105 processing occurs under basal conditions and increases following signaling. IκB kinase β (IKKβ) mediates phosphorylation at the C-terminal domain of p105, leads to accelerated processing and degradation of the precursor. A20 is a dual function deubiquitinating and ubiquitin ligating enzyme, involving in turning-off the NF-κB signaling pathway. Here we show that A20 suppresses TNFα-induced proteolysis of p105...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28922740/a-conserved-dggk-motif-is-essential-for-the-function-of-the-pglb-oligosaccharyltransferase-from-campylobacter-jejuni
#8
Yasmin Barre, Harald Nothaft, Cody Thomas, Xin Liu, Jianjun Li, Kenneth K S Ng, Christine M Szymanski
In Campylobacter jejuni, the PglB oligosaccharyltransferase catalyzes the transfer of a heptasaccharide from a lipid donor to asparagine within the D/E-X1-N-X2-S/T sequon (X1,2 ≠ P) or releases this heptasaccharide as free oligosaccharides (fOS). Using available crystal structures and sequence alignments, we identified a DGGK motif near the active site of PglB that is conserved among all Campylobacter species. We demonstrate that amino acid substitutions in the aspartate and lysine residues result in loss of protein glycosylation in the heterologous Escherichia coli system...
October 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28921512/dacomitinib-induced-diarrhea-targeting-chloride-secretion-with-crofelemer
#9
Ysabella Z A Van Sebille, Rachel J Gibson, Hannah R Wardill, Imogen A Ball, Dorothy M K Keefe, Joanne M Bowen
Dacomitinib, an irreversible small-molecule pan-ErbB TKI, has a high incidence of diarrhea which has been suggested to be due to chloride secretory mechanisms. Based on this hypothesis, crofelemer, an anti-secretory agent may be an effective intervention. T84 monolayers were treated with 1µM dacomitinib and 10µM crofelemer, and mounted into Ussing chambers for electrogenic ion analysis. Crofelemer attenuated increases in chloride secretion in cells treated with dacomitinib. Albino Wistar rats (n=48) were treated with 7...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28920921/increased-intracellular-proteolysis-reduces-disease-severity-in-an-er-stress-associated-dwarfism
#10
Lorna A Mullan, Ewa J Mularczyk, Louise H Kung, Mitra Forouhan, Jordan Ma Wragg, Royston Goodacre, John F Bateman, Eileithyia Swanton, Michael D Briggs, Raymond P Boot-Handford
The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28919859/the-dietary-constituent-falcarindiol-promotes-cholesterol-efflux-from-thp-1-macrophages-by-increasing-abca1-gene-transcription-and-protein-stability
#11
Limei Wang, Veronika Palme, Nicole Schilcher, Angela Ladurner, Elke H Heiss, Herbert Stangl, Rudolf Bauer, Verena M Dirsch, Atanas G Atanasov
We report increased cholesterol efflux from macrophages in the presence of falcarindiol, an important dietary constituent present in commonly used vegetables and medicinal plants. Falcarindiol (3-20 μM) increased cholesterol efflux from THP-1-derived macrophages. Western blot analysis showed an increased protein level of ABCA1 upon falcarindiol exposure. Quantitative real-time PCR revealed that also ABCA1 mRNA level rise with falcarindiol (10 μM) treatment. The effect of falcarindiol on ABCA1 protein as well as mRNA level were counteracted by co-treatment with BADGE, an antagonist of PPARγ...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28918742/a-new-concept-of-action-of-hemostatic-proteases-on-inflammation-neurotoxicity-and-tissue-regeneration
#12
REVIEW
L R Gorbacheva, E V Kiseleva, I G Savinkova, S M Strukova
Key hemostatic serine proteases such as thrombin and activated protein C (APC) are signaling molecules controlling blood coagulation and inflammation, tissue regeneration, neurodegeneration, and some other processes. By interacting with protease-activated receptors (PARs), these enzymes cleave a receptor exodomain and liberate new amino acid sequence known as a tethered ligand, which then activates the initial receptor and induces multiple signaling pathways and cell responses. Among four PAR family members, APC and thrombin mainly act via PAR1, and they trigger divergent effects...
July 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28918157/differential-proteomic-profiling-of-endometrium-and-plasma-indicate-the-importance-of-hydrolysis-in-bovine-endometritis
#13
Shi-Dong Zhang, Shu-Wei Dong, Dong-Sheng Wang, Chike F Oguejiofor, Ali A Fouladi-Nashta, Zhi-Qiang Yang, Zuo-Ting Yan
Endometritis is an important disease of dairy cows that leads to significant economic losses in the dairy cattle industry. To investigate the alteration of proteins associated with endometritis in the dairy cow, the isobaric tags for relative and absolute quantification (iTRAQ) technique was applied to quantitatively identify differentially expressed proteins (DEP) in the endometrium and peripheral plasma of Chinese Holstein cows with endometritis. Compared with the normal (control) group, 159 DEP in the endometrium and 137 DEP in the plasma were identified in cows with endometritis...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28918152/short-communication-influence-of-various-proteolytic-sources-during-fermentation-of-reconstituted-corn-grain-silages
#14
D Junges, G Morais, M H F Spoto, P S Santos, A T Adesogan, L G Nussio, J L P Daniel
The objective of this study was to determine the contribution of corn kernel enzymes, bacteria, fungi, and fermentation end-products (main acids and ethanol) to protein solubilization during fermentation of reconstituted corn grain silage. Flint corn kernels were ground (5-mm sieve), rehydrated to 32% of moisture, and treated with no additives (control), gamma irradiation (32 kGy), gamma irradiation + fermentation end-products (1% of lactic acid, 0.3% of acetic acid, and 0.7% of ethanol, as fed), and natamycin (1% as fed)...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28918135/effects-of-addition-of-malic-or-citric-acids-on-fermentation-quality-and-chemical-characteristics-of-alfalfa-silage
#15
W C Ke, W R Ding, D M Xu, L M Ding, P Zhang, F D Li, X S Guo
We studied the effects on alfalfa preservation and chemical composition of the addition of different levels of malic acid and citric acid at ensiling as well as the utilization efficiency of these 2 organic acids after fermentation. Alfalfa was harvested at early bloom stage. After wilting to a dry matter content of approximately 40%, the alfalfa was chopped into 1- to 2-cm pieces for ensiling. Four levels (0, 0.1, 0.5, and 1% of fresh weight) of malic acid or citric acid were applied to chopped alfalfa at ensiling with 4 replicates for each treatment, and the treated alfalfa forages were ensiled for 60 d in vacuum-sealed polyethylene bags (dimensions: 200 mm × 300 mm) packed with 200 to 230 g of fresh alfalfa per mini silo and an initial density of 0...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28916376/transcriptome-profiling-of-the-plutella-xylostella-lepidoptera-plutellidae-ovary-reveals-genes-involved-in-oogenesis
#16
Lu Peng, Lei Wang, Yi-Fan Yang, Ming-Min Zou, Wei-Yi He, Yue Wang, Qing Wang, Liette Vasseur, Min-Sheng You
BACKGROUND: As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops...
September 12, 2017: Gene
https://www.readbyqxmd.com/read/28916188/mast-cell-chymase-decreases-the-severity-of-group-b-streptococcus-infections
#17
Claire Gendrin, Nicholas J Shubin, Erica Boldenow, Sean Merillat, Morgan Clauson, Danny Power, Kelly S Doran, Magnus Abrink, Gunnar Pejler, Lakshmi Rajagopal, Adrian M Piliponsky
BACKGROUND: Group B Streptococcus (GBS) or Streptococcus agalactiae are ß-hemolytic, Gram-positive bacteria that colonize the lower genital tract of women and are frequently associated with infections during pregnancy. Innate immune defenses are critical for controlling GBS dissemination and systemic infection. Mast cells are resident sentinel cells that come into contact with pathogens early during colonization and infection. OBJECTIVE: We aimed to investigate the contribution of chymase to systemic GBS infection and rates of preterm birth...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28915727/the-protein-and-energy-metabolic-response-of-skeletal-muscle-to-the-low-protein-diets-in-growing-pigs
#18
Yinghui Li, Fengna Li, Yehui Duan, Qiuping Guo, Wenlong Wang, Chaoyue Wen, Xingguo Huang, Yulong Yin
This study was conducted to determine the effect of the low-protein diets on protein and energy metabolism in skeletal muscle, and to elucidate the underlying mechanism. A total of 18 growing pigs (average initial body weight = 36.47 kg) were individually penned and assigned to three treatments, each treatment was fed one of three diets containing either 18%, 15%, or 12% CP. The results showed that reducing dietary CP contents decreased (P < 0.05) the weight of half Longissimus dorsi (LD) muscle and serum concentration of insulin-like growth factor 1 (IGF-1)...
September 15, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28913881/effect-of-negative-dietary-cation-anion-differences-on-carcass-characteristics-and-beef-tenderness-of-japanese-black-steers
#19
Kyohei Ishida, Kazuo Hirano
Lowering dietary cation-anion differences (DCAD) can enhance responsiveness to Ca-homeostatic hormones and increase Ca availability, which might have potential to activate a Ca-dependent protease, calpain, and to enhance postmortem myofibrillar proteolysis. In this study, we investigated the effects of DCAD manipulation on calpain activity and beef tenderness in Japanese Black cattle which are characterized by their high marbling. Thirty-six Japanese Black steers were allotted to one of two treatments: (i) control (CON; DCAD +6...
September 15, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28912474/rhus-coriaria-increases-protein-ubiquitination-proteasomal-degradation-and-triggers-non-canonical-beclin-1-independent-autophagy-and-apoptotic-cell-death-in-colon-cancer-cells
#20
Khawlah Athamneh, Hussain El Hasasna, Halima Al Samri, Samir Attoub, Kholoud Arafat, Nehla Benhalilou, Asma Al Rashedi, Yusra Al Dhaheri, Synan AbuQamar, Ali Eid, Rabah Iratni
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Here, we investigated the anticancer effect of Rhus coriaria extract (RCE) on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE significantly inhibited the viability and colony growth of colon cancer cells. Moreover, RCE induced Beclin-1-independent autophagy and subsequent caspase-7-dependent apoptosis. Blocking of autophagy by chloroquine significantly reduced RCE-induced cell death, while blocking of apoptosis had no effect on RCE-induced cell death...
September 14, 2017: Scientific Reports
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