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Biological Chemistry

Cun-En Wu, Yu-Wen Zhuang, Jin-Yong Zhou, Shen-Lin Liu, Xi Zou, Jian Wu, Rui-Ping Wang, Peng Shu
The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1...
February 14, 2019: Biological Chemistry
Kale Kundert, Tanja Kortemme
The ability to engineer the precise geometries, fine-tuned energetics and subtle dynamics that are characteristic of functional proteins is a major unsolved challenge in the field of computational protein design. In natural proteins, functional sites exhibiting these properties often feature structured loops. However, unlike the elements of secondary structures that comprise idealized protein folds, structured loops have been difficult to design computationally. Addressing this shortcoming in a general way is a necessary first step towards the routine design of protein function...
January 24, 2019: Biological Chemistry
Sven Hofmann, Kathrin Bellmann-Sickert, Annette G Beck-Sickinger
As a very abundant neuropeptide in the brain and widely distributed peptide hormone in the periphery, neuropeptide Y (NPY) appears to be a multisignaling key peptide. Together with peptide YY, pancreatic polypeptide and the four human G protein-coupled receptor subtypes hY1R, hY2R, hY4R and hY5R it forms the NPY/hYR multiligand/multireceptor system, which is involved in essential physiological processes as well as in human diseases. In particular, NPY-induced hY1R signaling plays a central role in the regulation of food intake and stress response as well as in obesity, mood disorders and cancer...
January 17, 2019: Biological Chemistry
Harald Kolmar
No abstract available.
January 1, 2019: Biological Chemistry
Raquel Martin-Arevalillo, Teva Vernoux
Signalling molecules are produced, degraded, modified and transported throughout the development of higher organisms. Understanding their mode of action implies understanding these dynamics in vivo and in real time. Genetically encoded biosensors are being more and more used as tools to 'follow' signalling molecules and their responses inside an organism. This is the case for plants, where important progresses have been made in the development of such biosensors. Here, we summarize the main genetically encoded biosensors built for plant hormones, constructed using diverse components and steps of their signalling pathways...
December 4, 2018: Biological Chemistry
Darja Kanduc
Analyses of the peptide sharing between five common human viruses (Borna disease virus, influenza A virus, measles virus, mumps virus and rubella virus) and the human proteome highlight a massive viral vs. human peptide overlap that is mathematically unexpected. Evolutionarily, the data underscore a strict relationship between viruses and the origin of eukaryotic cells. Indeed, according to the viral eukaryogenesis hypothesis and in light of the endosymbiotic theory, the first eukaryotic cell (our lineage) originated as a consortium consisting of an archaeal ancestor of the eukaryotic cytoplasm, a bacterial ancestor of the mitochondria and a viral ancestor of the nucleus...
December 3, 2018: Biological Chemistry
Xiao-Hui Liu, Jie Ma, Jun-Xia Feng, Yun-Fang Zhang, Langxia Liu
Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we showed that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression...
December 1, 2018: Biological Chemistry
Xin Meng, Jack Clews, Anca D Cuitaa, Eleanor R Martin, Robert C Ford
CFTR (Cystic Fibrosis transmembrane conductance regulator) is a unique member of the ATP-binding cassette family of proteins because it has evolved into a channel. Mutations in CFTR cause cystic fibrosis, the most common genetic disease in people of European origins. The F508del mutation is found in about 90% of patients and here we present data that suggest its main effect is on CFTR stability rather than on the 3D folded state. A survey of recent cryo-electron microscopy studies was carried out and this highlighted differences in terms of CFTR conformation despite similarities in experimental conditions...
December 1, 2018: Biological Chemistry
Qiuyu Lin, Sen Hou, Yuyin Dai, Nan Jiang, Yingjie Lin
Parkinson's disease (PD) is a common neurological disorder characterized by dopaminergic (DA) neuron degeneration and death in the midbrain, and the long noncoding RNA HOTAIR has been shown to affect disease progression in PD. In this study, we aimed to further illustrate the molecular mechanism of HOTAIR in PD. Bioinformatics analysis was utilized to determine the potential downstream targets of HOTAIR in PD. Luciferase assay and RNA Binding Protein Immunoprecipitation (RIP) assay were used to validate the existence of binding sites between competing endogenous RNAs (ceRNAs)...
December 1, 2018: Biological Chemistry
Uwe Schlomann, Kristina Dorzweiler, Elisa Nuti, Tiziano Tuccinardi, Armando Rossello, Jörg W Bartsch
ADAM8 as a membrane-anchored metalloproteinase-disintegrin is upregulated under pathological conditions such as inflammation and cancer. As active sheddase, ADAM8 can cleave several membrane proteins, among them the low-affinity receptor FcεRII CD23. Hydroxamate-based inhibitors are routinely used to define relevant proteinases involved in ectodomain shedding of membrane proteins. However, for ADAM proteinases, common hydroxamates have variable profiles in their inhibition properties, commonly known for ADAM proteinases 9,10, and 17...
December 1, 2018: Biological Chemistry
Brian M Moran, Michael G Miskelly, Yasser H A Abdel-Wahab, Peter R Flatt, Aine M McKillop
The role of Zn2+-sensing receptor GPR39 on glucose homeostasis and incretin regulation was assessed in enteroendocrine L- and K-cells. Anti-hyperglycaemic, insulinotropic and incretin secreting properties of Zn2+ were explored in normal, diabetic and incretin receptor knockout mice. Compared to intraperitoneal injection, oral administration of Zn2+ (50 μmol/kg body weight) with glucose (18 mmol/kg) in lean mice reduced the glycaemic excursion by 25-34% (p<0.05-p<0.001) and enhanced glucose-induced insulin release by 46-48% (p<0...
December 1, 2018: Biological Chemistry
Chantal Chudoba, Kristina Wardelmann, André Kleinridders
The prevalence of obesity and its co-morbidities such as insulin resistance and type 2 diabetes are tightly linked to increased ingestion of palatable fat enriched food. Thus, it seems intuitive that the brain senses elevated amounts of fatty acids and affects adaptive metabolic response, which is connected to mitochondrial function and insulin signaling. This review will address the effect of dietary fatty acids on brain insulin and mitochondrial function with a special emphasis on the impact of different fatty acids on brain function and metabolism...
December 1, 2018: Biological Chemistry
Martin Prescher, Tim Kroll, Lutz Schmitt
Several ABC transporters of the human liver are responsible for the secretion of bile salts, lipids and cholesterol. Their interplay protects the biliary tree from the harsh detergent activity of bile salts. Among these transporters, ABCB4 is essential for the translocation of phosphatidylcholine lipids from the inner to the outer leaflet of the canalicular membrane of hepatocytes. ABCB4 deficiency can result in altered phosphatidylcholine to bile salt ratios, which led to intrahepatic cholestasis of pregnancy, low phospholipid associated cholelithiasis, drug induced liver injury or even progressive familial intrahepatic cholestasis type 3...
December 1, 2018: Biological Chemistry
Joana Pereira-Vieira, João Azevedo-Silva, Ana Preto, Margarida Casal, Odília Queirós
Monocarboxylate transporters (MCTs) inhibition leads to disruption in glycolysis, induces cell death and decreases cell invasion, revealing the importance of MCT activity in intracellular pH homeostasis and tumor aggressiveness. 3-bromopyruvate (3BP) is an antitumor agent, whose uptake occurs via MCTs. It was aim of this work to unravel the importance of extracellular conditions on MCTs regulation and in 3BP activity. HCT-15 was found to be the most sensitive cell line and also the one that presented the highest basal expression of both MCT1 and of its chaperone CD147...
December 1, 2018: Biological Chemistry
Xiaohui Xu, Xiaoyun Zhou, Chao Gao, Lei Cao, Ye Zhang, Xue Hu, Yushang Cui
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Understanding the mechanisms responsible for the malignancy of NSCLC cell is important for therapy and drug development. Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. We found that Nodal can trigger the proliferation of NSCLC cells and decrease the sensitivity to doxorubicin (Dox) and cisplatin (CDDP) treatment. Targeted inhibition of Nodal can suppress the proliferation of NSCLC cells...
December 1, 2018: Biological Chemistry
Ahmed Ashraf Moustafa Kamal, Monica Habib, Joerg Haupenthal, Rolf Wolfgang Hartmann, Martin Empting
RNA polymerase (RNAP) remains a relatively underexplored target with only rifampicin and fidaxomicin in clinical use. Hence, the concurrent rise in bacterial resistance rate urges the search for novel RNAP inhibitors with novel mode of action. In this work, we investigated the impact of several systematic modifications including sidechain-to-sidechain macrocylization in α-helical content and biological activity of a previously identified inhibitory sigma factor fragment. Ala-scan results, peptide truncation from both the N- and C- terminus, and modifications inspired by other RNAP inhibitors revealed novel structure activity relationships but did not yield a superior sequence...
December 1, 2018: Biological Chemistry
Jelle Vriend, Charlotte A Hoogstraten, Kevin R Venrooij, Bartholomeus T van den Berge, Larissa P Govers, Arno van Rooij, Marleen C D G Huigen, Tom J J Schirris, Frans G M Russel, Rosalinde Masereeuw, Martijn J Wilmer
Organic anion transporter (OAT) 1 and 3 are, besides uptake transporters, key in several cellular metabolic pathways. The underlying mechanisms are largely unknown. Hence, we used human conditionally immortalized proximal tubule epithelial cells (ciPTEC) overexpressing OAT1 or OAT3 to gain insight into these mechanisms. In ciPTEC-OAT1 and -OAT3, extracellular lactate levels were decreased (by 77% and 71%, respectively), while intracellular ATP levels remained unchanged, suggesting a shift towards an oxidative phenotype upon OAT1 or OAT3 overexpression...
December 1, 2018: Biological Chemistry
Raphael Trösch, Felix Willmund
Cells are highly adaptive systems that respond and adapt to changing environmental conditions such as temperature fluctuations or altered nutrient availability. Such acclimation processes involve reprogramming of the cellular gene-expression profile, tuning of protein synthesis, remodelling of metabolic pathways and morphological changes of the cell shape. Nutrient starvation can lead to limited energy supply and consequently, remodelling of protein synthesis is one of the key steps of regulation since the translation of the genetic code into functional polypeptides may consume up to 40% of a cell's energy during proliferation...
December 1, 2018: Biological Chemistry
Xingping Dai, Min Yi, Dongsheng Wang, Yanyi Chen, Xia Xu
The present study was designed to investigate the mechanism of traditional Chinese medicine Changqin NO. 1 on amelioration of traumatic brain injury (TBI). Adult male C57BL/6J mice and newborn mice were used to generate a mouse TBI model and harvest primary neurons, respectively. The localizations of specific neural markers neuropilin-1 (Nrp-1), growthassociated protein-43 (GAP-43) and microtubule-associated protein Tau (Tau) were examined in brain tissues by immunohistochemistry. TUNEL apoptotic cell detection in tissue sections and CCK-8 cell viability assay were performed to examine neuronal apoptosis...
December 1, 2018: Biological Chemistry
Markus Schweipert, Niklas Jänsch, Wisely Oki Sugiarto, Franz-Josef Meyer-Almes
HDAC8 is an established and validated target for T-cell lymphoma and childhood neuroblastoma. The active site binding pocket of HDAC8 is highly conserved among all zinccontaining representatives of the histone deacetylase family. This explains that most HDACs are unselectively recognized by similar inhibitors featuring a zinc binding group (ZBG), a hydrophobic linker and a head group. In the light of this difficulty, the creation of isoenzymeselectivity is one of the major challenges in the development of HDAC inhibitors...
December 1, 2018: Biological Chemistry
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