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Biological Chemistry

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https://www.readbyqxmd.com/read/28095368/iron-overload-and-altered-iron-metabolism-in-ovarian-cancer
#1
Stephanie Rockfield, Joseph Raffel, Radhe Mehta, Nabila Rehman, Meera Nanjundan
Iron is an essential element required for many processes within the cell. Dysregulation in iron homeostasis due to iron overload is detrimental. This nutrient is postulated to contribute to the initiation of cancer; however, the mechanisms by which this occurs remain unclear. Defining how iron promotes the development of ovarian cancers from precursor lesions is essential for developing novel therapeutic strategies. In this review, we discuss (1) how iron overload conditions may initiate ovarian cancer development, (2) dysregulated iron metabolism in cancers, (3) the interplay between bacteria, iron, and cancer, and (4) chemotherapeutic strategies targeting iron metabolism in cancer patients...
January 14, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28095367/micrornas-are-important-regulators-of-drug-resistance-in-colorectal-cancer
#2
Yang Zhang, Jing Wang
Despite of continuous development of cancer treatment over the past decades, drug resistance is still one of the major hurdles of effective therapy for advanced colorectal cancer (CRC) worldwide and the understanding of its underlying mechanisms remains limited. Emerged data suggests that many microRNAs (miRNAs) may contribute to drug resistance in CRC. Major findings on miRNA functions in drug resistance of CRC are systemically reviewed here, with the goal of providing new updates to broaden our comprehension of its mechanisms and evidence to utilize miRNAs as potential therapeutic targets for CRC treatment...
January 14, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28085670/when-how-and-why-regulated-proteolysis-by-the-essential-ftsh-protease-in-escherichia-coli
#3
Lisa-Marie Bittner, Jan Arends, Franz Narberhaus
Cellular proteomes are dynamic and adjusted to permanently changing conditions by ATP-fueled proteolytic machineries. Among the five AAA+ proteases in Escherichia coli FtsH is the only essential and membrane-anchored metalloprotease. FtsH is a homohexamer that uses its ATPase domain to unfold and translocate substrates that are subsequently degraded without the need of ATP in the proteolytic chamber of the protease domain. FtsH eliminates misfolded proteins in the context of general quality control and properly folded proteins for regulatory reasons...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27935845/stability-and-aggregation-propensity-do-not-fully-account-for-the-association-of-various-germline-variable-domain-gene-segments-with-light-chain-amyloidosis
#4
Sergio A Garay Sánchez, Francisco Javier Rodríguez Álvarez, Guadalupe Zavala-Padilla, Luz María Mejia-Cristobal, Armando Cruz-Rangel, Miguel Costas, D Alejandro Fernández Velasco, Jorge Melendez-Zajgla, Luis Del Pozo-Yauner
Variable domain (VL) gene segments exhibit variable tendencies to be associated with light chain amyloidosis (AL). While few of them are very frequent in AL and give rise to most of the amyloidogenic light chains compiled at the sequence databases, other are rarely found among the AL cases. To analyze to which extent these tendencies depend on folding stability and aggregation propensity of the germline VL protein, we characterized VL proteins encoded by four AL-associated germline gene segments and one not associated to AL...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27926477/intra-or-extra-exosomal-secretion-of-hdgf-isoforms-the-extraordinary-function-of-the-hdgf-a-n-terminal-peptide
#5
Jessica Nüße, Eva-Maria Blumrich, Ursula Mirastschijski, Lennart Kappelmann, Sørge Kelm, Frank Dietz
Hepatoma-derived growth factor (HDGF) is a protein with diverse intracellular functions. Moreover, after non-conventional secretion, extracellular HDGF is able to influence different signaling pathways, leading for example to induction of processes like epithelial-mesenchymal transition (EMT) and cell migration. Intriguingly, in recent proteome studies, HDGF was also found secreted by special microvesicles called exosomes. Recently, we demonstrated the existence of two new HDGF isoforms (B and C). These isoforms are involved in different cellular processes than HDGF-A...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27926476/mitochondrial-cytochrome-c-oxidase-is-inhibited-by-atp-only-at-very-high-atp-adp-ratios
#6
Rabia Ramzan, Andreas K Schaper, Petra Weber, Annika Rhiel, Muhammad Saad Siddiq, Sebastian Vogt
In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP-dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27902449/is-n-n-dimethylglycine-n-oxide-a-choline-and-betaine-metabolite
#7
Michael Lever, Christopher J McEntyre, Peter M George, Stephen T Chambers
Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved. We synthesized the N-oxide of dimethylglycine (DMGO) by oxidizing dimethylglycine with peracetic acid, and measured DMGO in human plasma and urine by HPLC-MS/MS with positive ion detection, using two chromatography procedures, based on ion exchange and HILIC separations...
January 13, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28076289/from-bacteria-to-chloroplasts-evolution-of-the-chloroplast-srp-system
#8
Dominik Ziehe, Beatrix Dünschede, Danja Schünemann
Chloroplasts derive from a prokaryotic symbiont that lost most of its genes during evolution. As a result, the great majority of chloroplast proteins are encoded in the nucleus and are posttranslationally imported into the organelle. The chloroplast genome encodes only a few proteins. These include several multispan thylakoid membrane proteins which are synthesized on thylakoid-bound ribosomes and cotranslationally inserted into the membrane. During evolution, ancient prokaryotic targeting machineries were adapted and combined with novel targeting mechanisms to facilitate post- and cotranslational protein transport in chloroplasts...
January 10, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27935848/plasmin-ogen-serves-as-a-favorable-biomarker-for-prediction-of-survival-in-advanced-high-grade-serous-ovarian-cancer
#9
Shuo Zhao, Julia Dorn, Rudolf Napieralski, Axel Walch, Sandra Diersch, Matthias Kotzsch, Nancy Ahmed, John D Hooper, Marion Kiechle, Manfred Schmitt, Viktor Magdolen
In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed...
January 6, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28051995/in-vitro-modelling-of-familial-amyloidotic-polyneuropathy-allows-quantitative-detection-of-transthyretin-amyloid-fibril-like-structures-in-hepatic-derivatives-of-patient-specific-induced-pluripotent-stem-cells
#10
Jeannine Hoepfner, Mandy Kleinsorge, Oliver Papp, Susanne Alfken, Robin Heiringhoff, Andreas Pich, Vanessa Sauer, Andree Zibert, Gudrun Göhring, Hartmut Schmidt, Malte Sgodda, Tobias Cantz
The transthyretin protein is thermodynamically destabilised by mutations in the transthyretin gene, promoting the formation of amyloid fibrils in various tissues. Consequently, impaired autonomic organ function is observed in patients suffering from transthyretin-related Familial Amyloidotic Polyneuropathy (FAP). The influence of individual genetic backgrounds on fibril formation as a potential cause of genotype-phenotype variations needs to be investigated in order to ensure efficient patient-specific therapies...
January 4, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27865090/characterization-of-the-subcellular-localization-and-nuclear-import-molecular-mechanisms-of-herpes-simplex-virus-1-ul2
#11
Mingsheng Cai, Zebin Huang, Zongmin Liao, Tao Chen, Ping Wang, Si Jiang, Daixiong Chen, Tao Peng, Yun Bian, Gengde Hong, Hang Yang, Zhancheng Zeng, Xiaowei Li, Meili Li
As a crucial protein, the herpes simplex virus 1 (HSV-1) UL2 protein has been shown to take part in various stages of viral infection, nonetheless, its exact subcellular localization and transport molecular determinants are not well known thus far. In the present study, by using live cells fluorescent microscopy assay, UL2 tagged with enhanced yellow fluorescent protein was transiently expressed in live cells and showed a completely nuclear accumulation without the presence of other HSV-1 proteins. Moreover, the nuclear transport of UL2 was characterized to be assisted by multiple transport pathways through Ran-, importin α1-, α5-, α7-, β1- and transportin-1 cellular transport receptors...
December 28, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27845877/substrate-processing-in-intramembrane-proteolysis-by-%C3%AE-secretase-the-role-of-protein-dynamics
#12
Dieter Langosch, Harald Steiner
Intramembrane proteases comprise a number of different membrane proteins with different types of catalytic sites. Their common denominator is cleavage within the plane of the membrane, which usually results in peptide bond scission within the transmembrane helices of their substrates. Despite recent progress in the determination of high-resolution structures, as illustrated here for the γ-secretase complex and its substrate C99, it is still unknown how these enzymes function and how they distinguish between substrates and non-substrates...
December 28, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/28002022/interface-analysis-of-small-gtp-binding-protein-complexes-suggests-preferred-membrane-orientations
#13
Ingrid R Vetter
Crystal structures of small GTP binding protein complexes with their effectors and regulators reveal that one particularly flat side of the G domain that contains helix α4 and the C-terminal helix α5 is practically devoid of contacts. Although this observation seems trivial since the main binding targets are the switch I and II regions opposite of this side, the fact that all interacting proteins, even the largest ones, seem to avoid occupying this area (except for Ran, that does not localize to membranes) is quite striking...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/28002019/lysosomes-in-programmed-cell-death-pathways-from-initiators-to-amplifiers
#14
Nežka Kavčič, Katarina Pegan, Boris Turk
Lysosome is the central organelle for intracellular degradation of biological macromolecules and organelles. The material destined for degradation enters the lysosomes primarily via endocytosis, autophagy and phagocytosis, and is degraded through the concerted action of more than 50 lysosomal hydrolases. However, lysosomes are also linked with numerous other processes, including cell death, inflammasome activation and immune response, as well as with lysosomal secretion and cholesterol recycling. Among them programmed cell death pathways including apoptosis have received major attention...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27935847/structure-based-development-of-pde%C3%AE-inhibitors
#15
Pablo Martín-Gago, Eyad Kalawy Fansa, Alfred Wittinghofer, Herbert Waldmann
The prenyl binding protein PDEδ enhances the diffusion of farnesylated Ras proteins in the cytosol, ultimately affecting their correct localization and signaling. This has turned PDEδ into a promising target to prevent oncogenic KRas signaling. In this review we summarize and describe the structure-guided-development of the three different PDEδ inhibitor chemotypes that have been documented so far. We also compare both their potency for binding to the PDEδ pocket and their in vivo efficiency in suppressing oncogenic KRas signaling, as a result of the inhibition of the PDEδ/KRas interaction...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27811341/the-insect-derived-antimicrobial-peptide-metchnikowin-targets-fusarium-graminearum-%C3%AE-1-3-glucanosyltransferase-gel1-which-is-required-for-the-maintenance-of-cell-wall-integrity
#16
Mohammad-Reza Bolouri Moghaddam, Andreas Vilcinskas, Mohammad Rahnamaeian
Antimicrobial peptides (AMPs) are essential components of the insect innate immune system. Their diversity provides protection against a broad spectrum of microbes and they have several distinct modes of action. Insect-derived AMPs are currently being developed for both medical and agricultural applications, and their expression in transgenic crops confers resistance against numerous plant pathogens. The antifungal peptide metchnikowin (Mtk), which was originally discovered in the fruit fly Drosophila melanogaster, is of particular interest because it has potent activity against economically important phytopathogenic fungi of the phylum Ascomycota, such as Fusarium graminearum, but it does not harm beneficial fungi such as the mycorrhizal basidiomycete Piriformospora indica...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27805907/human-and-rodent-aryl-hydrocarbon-receptor-ahr-from-mediator-of-dioxin-toxicity-to-physiologic-ahr-functions-and-therapeutic-options
#17
Karl Walter Bock
Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27622830/a-role-for-the-metalloprotease-invadolysin-in-insulin-signaling-and-adipogenesis
#18
Ching-Wen Chang, Kanishk Abhinav, Francesca Di Cara, Ioanna Panagakou, Sharron Vass, Margarete M S Heck
Invadolysin is a novel metalloprotease conserved amongst metazoans that is essential for life in Drosophila. We previously showed that invadolysin was essential for the cell cycle and cell migration, linking to metabolism through a role in lipid storage and interaction with mitochondrial proteins. In this study we demonstrate that invadolysin mutants exhibit increased autophagy and decreased glycogen storage - suggestive of a role for invadolysin in insulin signaling in Drosophila. Consistent with this, effectors of insulin signaling were decreased in invadolysin mutants...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27611767/recent-insights-into-nitrite-signaling-processes-in-blood
#19
Christine C Helms, Xiaohua Liu, Daniel B Kim-Shapiro
Nitrite was once thought to be inert in human physiology. However, research over the past few decades has established a link between nitrite and the production of nitric oxide (NO) that is potentiated under hypoxic and acidic conditions. Under this new role nitrite acts as a storage pool for bioavailable NO. The NO so produced is likely to play important roles in decreasing platelet activation, contributing to hypoxic vasodilation and minimizing blood-cell adhesion to endothelial cells. Researchers have proposed multiple mechanisms for nitrite reduction in the blood...
December 21, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/28002024/the-cancer-cell-adhesion-resistome-mechanisms-targeting-and-translational-approaches
#20
Ellen Dickreuter, Nils Cordes
Cell adhesion-mediated resistance limits the success of cancer therapies and is a great obstacle to overcome in the clinic. Since the 90s, where it became clear that adhesion of tumor cells to the extracellular matrix is an important mediator of therapy resistance, a lot of work has been conducted to understand the fundamental underlying mechanisms and two paradigms were deduced: cell adhesion-mediated radioresistance (CAM-RR) and cell adhesion-mediated drug resistance (CAM-DR). Preclinical work has evidently demonstrated that targeting of integrins, adapter proteins and associated kinases comprising the cell adhesion resistome is a promising strategy to sensitize cancer cells to both radiotherapy and chemotherapy...
December 20, 2016: Biological Chemistry
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