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Biochimie

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https://www.readbyqxmd.com/read/28528273/addition-of-thiols-to-the-double-bond-of-dipeptide-c-terminal-dehydroalanine-as-a-source-of-new-inhibitors-of-cathepsin-c
#1
Paweł Lenartowicz, Maciej Makowski, Bartosz Oszywa, Kinga Haremza, Rafał Latajka, Małgorzata Pawełczak, Paweł Kafarski
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors...
May 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28528272/glycosylation-is-important-for-legumain-localization-and-processing-to-active-forms-but-not-for-cystatin-e-m-inhibitory-functions
#2
Ngoc Nguyen Lunde, Mads Haugland Haugen, Kristina Broe Bodin Larsen, Ingrid Damgaard, Solveig J Pettersen, Roya Kasem, Wioletta Rut, Marcin Drag, Marcin Poreba, Harald Thidemann Johansen, Rigmor Solberg
The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated. However, little is known about the nature of the carbohydrate groups and whether they affect the functions of these proteins. In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied. HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys. To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types...
May 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28528271/exploring-binding-characteristics-and-the-related-competition-of-different-protein-bound-uremic-toxins
#3
Olivier Deltombe, Henriette de Loor, Griet Glorieux, Annemieke Dhondt, Wim Van Biesen, Björn Meijers, Sunny Eloot
Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i...
May 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28522365/knowns-and-unknowns-of-membrane-lipid-synthesis-in-streptomycetes
#4
Mario Sandoval-Calderón, Ziqiang Guan, Christian Sohlenkamp
Bacteria belonging to the genus Streptomyces are among the most prolific producers of antibiotics. Research on cellular membrane biosynthesis and turnover is lagging behind in Streptomyces compared to related organisms like Mycobacterium tuberculosis. While natural products discovery in Streptomyces is evidently a priority in order to discover new antibiotics to combat the increase in antibiotic resistant pathogens, a better understanding of this cellular compartment should provide insights into the interplay between core and secondary metabolism...
May 15, 2017: Biochimie
https://www.readbyqxmd.com/read/28487136/role-of-micrornas-in-type-2-diabetes-and-associated-vascular-complications
#5
REVIEW
Joyita Banerjee, Vijay Nema, Yogita Dhas, Neetu Mishra
Type 2 diabetes mellitus (T2DM) has become a major health threat worldwide. MicroRNAs (miRNAs) are a group of non-coding RNAs known to regulate various biological processes including the pathogenesis of T2DM. Recent studies have pointed out that specific miRNAs play a critical role in controlling β cell activities and the development of diabetic vascular complications. Their association with the disease pathogenesis and omnipresence in body fluids have made them important players for prognosis, diagnosis and management of T2DM...
May 6, 2017: Biochimie
https://www.readbyqxmd.com/read/28487135/estrogen-enhanced-apical-and-basolateral-secretion-of-apolipoprotein-b-100-by-polarized-trophoblast-derived-bewo-cells
#6
Miriam Kamper, Florian Mittermayer, Rosalinda Cabuk, Katharina Gelles, Isabella Ellinger, Marcela Hermann
Cholesterol is an important nutrient for fetal development and transplacental transport occurs at all stages of human pregnancy. Furthermore, cholesterol is required for membrane building as well as steroid hormone synthesis. Therefore, all placental cell types require cholesterol for proper function. In human term placenta, the syncytiotrophoblast (STB) faces the maternal circulation. Uptake of maternal-derived cholesterol at the apical membrane of the STB is well understood, but the route by which cholesterol exits at the basal side for subsequent transfer across the fetal endothelial cells (FEC) or to other placental cell types remains not well characterized...
May 6, 2017: Biochimie
https://www.readbyqxmd.com/read/28483690/characterization-of-the-lipid-envelope-of-exosome-encapsulated-hev-particles-protected-from-the-immune-response
#7
Sabine Chapuy-Regaud, Martine Dubois, Célia Plisson-Chastang, Tiffany Bonnefois, Sébastien Lhomme, Justine Bertrand-Michel, Bruno You, Steve Simoneau, Pierre-Emmanuel Gleizes, Benoît Flan, Florence Abravanel, Jacques Izopet
The hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide. Although HEV is a small, naked RNA virus, HEV particles become associated with lipids in the blood of infected patients and in the supernatant of culture systems. The egress of these particles from cells implies the exocytosis pathway but the question of the role of the resulting HEV RNA containing exosomes and the nature of the lipids they contain has not been fully addressed. We determined the lipid proportions of exosomes from uninfected and HEV-infected cells and their role in HEV spreading...
May 5, 2017: Biochimie
https://www.readbyqxmd.com/read/28483689/the-c-terminus-of-ribosomal-protein-us4-contributes-to-small-ribosomal-subunit-biogenesis-and-the-fidelity-of-translation
#8
Divya Kamath, Benjamin B Allgeyer, Steven T Gregory, Margaret C Bielski, David M Roelofsz, Sharon L Sabapathypillai, Nikhil Vaid, Michael O'Connor
Ribosomal protein uS4 is an essential ribosomal component involved in multiple functions, including mRNA decoding. Structural analyses indicate that during decoding, the interface between the C-terminus of uS4 and protein uS5 is disrupted and in agreement with this, C-terminal uS4 truncation mutants are readily isolated on the basis of their increased miscoding phenotypes. The same mutants can also display defects in small subunit assembly and 16S rRNA processing and some are temperature sensitive for growth...
May 5, 2017: Biochimie
https://www.readbyqxmd.com/read/28483688/specific-roles-of-phosphatidylglycerols-in-hosts-and-microbes
#9
REVIEW
Isabelle Dugail, Brandon D Kayser, Marie Lhomme
Phosphatidylglycerols (PGs) are specific phospholipids bearing negatively charged polar headgroups. Although recognized for long as a major lipid component of membranes in bacteria, it is considered a minor lipid in higher eukaryotes, due to its low abundance in biological fluids or tissues. However, new sensitive lipidomic approaches now provide tools for accurate quantification of PGs in biological samples, and this is likely to uncover new roles for these phospholipids in the near future. This paper reviews our present knowledge in PG function, from studies in microbes and eukaryotic cells, and gathers in one place a diverse range of information spread across many fields...
May 5, 2017: Biochimie
https://www.readbyqxmd.com/read/28479106/characterization-of-linear-mimetic-peptides-of-interleukin-22-from-dissection-of-protein-interfaces
#10
Sara La Manna, Pasqualina Liana Scognamiglio, Concetta Di Natale, Marilisa Leone, Flavia Anna Mercurio, Anna Maria Malfitano, Francesca Cianfarani, Stefania Madonna, Sergio Caravella, Cristina Albanesi, Ettore Novellino, Daniela Marasco
Interleukin-22 (IL-22) belongs to the family of IL-10 cytokines and is involved in a wide number of human diseases, including inflammatory disorders and cancer pathology. The ligand-receptor complex IL-22/IL-22R plays a key role in several pathways especially in the regulation and resolution of immune responses. The identification of novel compounds able to modulate IL-22/IL-22R complex could open the route to new therapeutic strategies in multiple human diseases. In this study, we designed and characterized IL-22 derived peptides at protein interface regions: several sequences revealed able to interfere with the protein complex with IC50 in the micromolar range as evaluated through Surface Plasmon Resonance (SPR) experiments...
May 4, 2017: Biochimie
https://www.readbyqxmd.com/read/28478110/empirical-genome-evolution-models-root-the-tree-of-life
#11
Ajith Harish, Charles G Kurland
A reliable phylogenetic reconstruction of the evolutionary history of contemporary species depends on a robust identification of the universal common ancestor (UCA) at the root of the Tree of Life (ToL). That root polarizes the tree so that the evolutionary succession of ancestors to descendants is discernable. In effect, the root determines the branching order and the direction of character evolution. Typically, conventional phylogenetic analyses implement time-reversible models of evolution for which character evolution is un-polarized...
May 3, 2017: Biochimie
https://www.readbyqxmd.com/read/28478109/the-role-of-de-novo-protein-synthesis-and-sirt1-in-er-stress-induced-atf4-and-chop-mrna-expression-in-mammalian-cells
#12
Stanley M H Chan, Xuechan Zhao, Abdulsalam Elfowiris, Cherubina Ratnam, Terence P Herbert
Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in the pathogenesis of many common human diseases. Integral to the UPR and an important determinant in cell fate is the expression of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This is promoted by activating transcription factor 4 (ATF4) whose expression is rapidly up-regulated in response to ER stress through an eIF2α phosphorylation-dependent increase in protein synthesis...
May 3, 2017: Biochimie
https://www.readbyqxmd.com/read/28478108/two-eucommia-farnesyl-diphosphate-synthases-exhibit-distinct-enzymatic-properties-leading-to-end-product-preferences
#13
Hiroyuki Kajiura, Nobuaki Suzuki, Yuji Tokumoto, Takuya Yoshizawa, Shinya Takeno, Kazuhito Fujiyama, Yoshinobu Kaneko, Hiroyoshi Matsumura, Yoshihisa Nakazawa
Farnesyl diphosphate synthase (FPS) is an essential enzyme in the biosynthesis of prenyl precursors for the production of primary and secondary metabolites and for the modification of proteins. Here we identified and characterized two FPSs (EuFPS1 and EuFPS2) from the plant Eucommia ulmoides. The EuFPSs had seven highly conserved prenyltransferase-specific domains that are critical for activity. Complementation and biochemical analyses using bacterially produced recombinant EuFPS isoforms showed that the EuFPSs had FPP synthesis activities both in vivo and in vitro...
May 3, 2017: Biochimie
https://www.readbyqxmd.com/read/28467890/brown-and-brite-adipocytes-same-function-but-different-origin-and-response
#14
REVIEW
Dinh-Toi Chu, Barbara Gawronska-Kozak
Inducing brown adipocytes in white adipose tissues is a promising target to combat obesity and its related disorders in human beings. This goal has been especially encouraged by new important discoveries of human brown adipose tissues. The accumulating evidence confirms the presence of active brown adipocytes, not only in newborns, but also in adult humans. In rodents, there are two populations of the Ucp1-expressing adipocytes with well characterized-thermogenic functions, classical interscapular brown adipocytes and brite/beige adipocytes (brown adipocytes that are induced in white adipose tissues)...
April 30, 2017: Biochimie
https://www.readbyqxmd.com/read/28465215/glycogen-synthase-from-the-parabasalian-parasite-trichomonas-vaginalis-an-unusual-member-of-the-starch-glycogen-synthase-family
#15
Wayne A Wilson, Prajakta Pradhan, Nayasha Madhan, Galen C Gist, Andrew Brittingham
Trichomonas vaginalis, a parasitic protist, is the causative agent of the common sexually-transmitted infection trichomoniasis. The organism has long been known to synthesize substantial glycogen as a storage polysaccharide, presumably mobilizing this compound during periods of carbohydrate limitation, such as might be encountered during transmission between hosts. However, little is known regarding the enzymes of glycogen metabolism in T. vaginalis. We had previously described the identification and characterization of two forms of glycogen phosphorylase in the organism...
April 29, 2017: Biochimie
https://www.readbyqxmd.com/read/28461155/akaryotes-and-eukaryotes-are-independent-descendants-of-a-universal-common-ancestor
#16
Ajith Harish, Charles G Kurland
We reconstructed a global tree of life (ToL) with non-reversible and non-stationary models of genome evolution that root trees intrinsically. We implemented Bayesian model selection tests and compared the statistical support for four conflicting ToL hypotheses. We show that reconstructions obtained with a Bayesian implementation (Klopfstein et al., 2015) is consistent with reconstructions obtained with an empirical Sankoff parsimony (ESP) implementation (Harish et al. 2013). Both are based on the genome contents of coding sequences for protein domains (superfamilies) from hundreds of genomes...
April 28, 2017: Biochimie
https://www.readbyqxmd.com/read/28457944/effects-of-phenothiazine-structured-compounds-on-app-processing-in-alzheimer-s-disease-cellular-model
#17
Melike Yuksel, Kevser Biberoglu, Seda Onder, K Gonca Akbulut, Ozden Tacal
The excess accumulation of amyloid-β (Aβ) peptides derived from the sequential cleavage of amyloid precursor protein (APP) by secretases, is one of the toxic key events leading to neuronal loss in Alzheimer's disease (AD). Studies have shown that cholinergic activity may also be involved in the regulation of APP metabolism. In the current study, we have investigated the roles of toluidine blue O (TBO) and thionine (TH), newly recognized phenothiazine-derived cholinesterase inhibitors, on the metabolism of APP in Chinese hamster ovary cells stably expressing human APP751 and presenilin 1 (PS70 cells)...
April 27, 2017: Biochimie
https://www.readbyqxmd.com/read/28457943/actin-cytoskeleton-mediates-bmp2-smad-signaling-via-calponin-1-in-preosteoblast-under-simulated-microgravity
#18
Hongjie Xu, Feng Wu, Hongyu Zhang, Chao Yang, Kai Li, Hailong Wang, Honghui Yang, Yue Liu, Bai Ding, Yingjun Tan, Ming Yuan, Yinghui Li, Zhongquan Dai
Microgravity influences the activity of osteoblast, induces actin microfilament disruption and leads to bone loss during spaceflight. Mechanical stress such as gravity, regulates cell function, response and differentiation through dynamic cytoskeleton changes, but the mechanotransduction mechanism remains to be fully elucidated. Previous, we demonstrated actin microfilament mediated osteoblast Cbfa1 responsiveness to BMP2 under simulated microgravity (SMG). Here, we explored a potential molecular and its detailed mechanism of actin cytoskeleton functioning on BMP2-Smad signaling in MC3T3-E1 under SMG...
April 27, 2017: Biochimie
https://www.readbyqxmd.com/read/28456710/microrna-149-is-associated-with-clinical-outcome-in-human-neuroblastoma-and-modulates-cancer-cell-proliferation-through-rap1-independent-of-mycn-amplification
#19
Yali Xu, Xinghe Chen, Li Lin, Hong Chen, Shuping Yu, Dumiao Li
PURPOSE: We evaluated the clinical relevance of microRNA-149 (miR-149) in neuroblastoma (NB) and its functional roles in regulating NB proliferation in vitro. METHODS: QRT-PCR was used to evaluate miR-149 expression in NB cell lines and primary NB tumors. Association between endogenous miR-149 expression in primary NB tumors and their host patients' clinicopathological factors and overall survival (OS) were statistically evaluated. In SH-SY5Y, an MYCN-non-amplified, and LAN5, an MYCN-amplified NB cell lines, miR-149 was either upregulated or downregulated by lentiviral transduction, to evaluate its effect on NB proliferation in vitro...
April 26, 2017: Biochimie
https://www.readbyqxmd.com/read/28454919/new-amino-acid-schiff-base-derived-from-s-allyl-cysteine-and-methionine-alleviates-carbon-tetrachloride-induced-liver-dysfunction
#20
Periyasamy Ratha, Loganathan Chitra, Ancy Iruthayaraj, Poomani Kumaradhas, Thayumanavan Palvannan
In spite of the tremendous stride in modern medicine, conventional drugs used in the hepatotoxic management are mostly inadequate. The present study aims in the synthesis of novel Schiff base compound derived using s-ally cystiene and methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1-carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was characterized using UV-visible spectrophotometer, FTIR, (1)HNMR, and GC-MS. ACEMB showed potent in vitro antioxidant property. Chronic administration of ACEMB prior to CCl4 intoxication: i) attenuated the leakage of liver injury markers, such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into the blood circulation; ii) normalized the concentration of total proteins, albumin and globulin to control level; and iii) protected the liver against dyslipidemia...
April 25, 2017: Biochimie
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