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Biochimica et Biophysica Acta

C Rupp, K A Bode, Y Leopold, P Sauer, D N Gotthardt
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin. Previous bile proteomic analyses in patients with PSC have revealed changes in disease activity specific to malignant transformation. In this study, we established a reference bile duct-derived bile proteome for PSC that can be used to evaluate biliary pathophysiology. Samples were collected from patients with PSC or with choledocholithiasis (control) (n=6 each). Furthermore, patients with PSC-associated cholangiocarcinoma (CC) and with CC without concomitant PSC were analyzed...
September 21, 2017: Biochimica et Biophysica Acta
W F Theeuwes, H R Gosker, R C J Langen, K J P Verhees, N A M Pansters, A M W J Schols, A H V Remels
BACKGROUND: Aberrant skeletal muscle mitochondrial oxidative metabolism is a debilitating feature of chronic diseases such as chronic obstructive pulmonary disease, type 2 diabetes and chronic heart failure. Evidence in non-muscle cells suggests that glycogen synthase kinase-3β (GSK-3β) represses mitochondrial biogenesis and inhibits PPAR-γ co-activator 1 (PGC-1), a master regulator of cellular oxidative metabolism. The role of GSK-3β in the regulation of skeletal muscle oxidative metabolism is unknown...
September 21, 2017: Biochimica et Biophysica Acta
Xiuna Yang, Lijie Wu, Yajun Ran, Ao Xu, Bing Zhang, Xiaolin Yang, Rongguang Zhang, Zihe Rao, Jun Li
l-arginine is used as a source of both carbon and nitrogen in Mycobacterium tuberculosis (Mtb) and its biosynthesis is essential for the pathogen's survival. MtbArgA (Rv2747) catalyzes the initial step in l-arginine biosynthesis by transferring an acetyl group from acetyl coenzyme A (AcCoA) to l-glutamate. MtbArgA is a class III N-acetylglutamate synthase (NAGS) with no structural information. Here, we solved the crystal structure of MtbArgA complexed with AcCoA and l-glutamate. The overall structure adopts a classic fold of the GCN5-related N-acetyltransferase (GNAT) family, characterized by a "V"-shaped cleft and β-bulge, but uses distinct residues for the binding and reaction of AcCoA...
September 21, 2017: Biochimica et Biophysica Acta
Ahmed Bulldan, Viveka Nand Malviya, Neha Upmanyu, Lutz Konrad, Georgios Scheiner-Bobis
ZIP9 is a Zn(2+) transporter, testosterone receptor, and mediator of signaling events through G-proteins. Despite these pivotal properties, however, its physiological and pathophysiological significance has not yet been comprehensively addressed. Using a cell line that lacks the classical androgen receptor we show that ZIP9-mediated phosphorylation of Erk1/2, CREB, or ATF-1 and expression of claudin-5 and zonula occludens-1 by testosterone can be completely antagonized by bicalutamide (Casodex), an anti-androgen of significant clinical impact...
September 21, 2017: Biochimica et Biophysica Acta
Maria Nathália Moraes, Leonardo Vinicius Monteiro de Assis, Felipe Dos Santos Henriques, Miguel Luiz Batista Junior, Ali D Güler, Ana Maria de Lauro Castrucci
Transient receptor potential (TRP) channels are known to regulate energy metabolism, and TRPM8 has become an interesting player in this context. Here we demonstrate the role of the cold sensor TRPM8 in the regulation of clock gene and clock controlled genes in brown adipose tissue (BAT). We investigated TrpM8 temporal profile in the eyes, suprachiasmatic nucleus and BAT; only BAT showed temporal variation of TrpM8 transcripts. Eyes from mice lacking TRPM8 lost the temporal profile of Per1 in LD cycle. This alteration in the ocular circadian physiology may explain the delay in the onset of locomotor activity in response to light pulse, as compared to wild type animals (WT)...
September 21, 2017: Biochimica et Biophysica Acta
Lindsay Johnson, Tyler Wilkinson, Paolo Arosio, Artem Melman, Fadi Bou-Abdallah
BACKGROUND: Ferritins are ubiquitous multi-subunit iron storage and detoxification proteins that play a critical role in iron homeostasis. Ferrous ions that enter the protein's shell through hydrophilic channels are rapidly oxidized at dinuclear centers on the H-subunit before transfer to the protein's cavity for storage. The mechanisms of iron loading have been extensively studied but little is known about iron mobilization. Fe(III) reduction can occur via rapid reduction by suitable reducing agents followed by chelation of Fe(II) ions or via direct and slow Fe(III) chelation...
September 21, 2017: Biochimica et Biophysica Acta
Yan Zhang, Deying Zeng, Jiaojiao Cao, Mingxue Wang, Bing Shu, Guotao Kuang, Tian-Miao Ou, Jia-Heng Tan, Lian-Quan Gu, Zhi-Shu Huang, Ding Li
BACKGROUND: Telomeric repeat-containing RNA (TERRA) is a large non-coding RNA in mammalian cells, which forms an integral component of telomeric heterochromatin. TERRA can bind to an allosteric site of telomeric repeat factor 2 (TRF2), a key component of Shelterin that protect chromosome termini. Both TERRA and TRF2 have been recognized as promising new therapeutic targets for cancer treatment. METHODS: Our methods include FRET assay, SPR, CD, microscale thermophoresis (MST), enzyme-linked immunosorbent assay (ELISA), chromatin immunoprecipitation (ChIP), colony formation assays, Western blot, immunofluorescence, cell cycle arrest and apoptosis detection, and xCELLigence real-time cell analysis (RTCA)...
September 21, 2017: Biochimica et Biophysica Acta
Deepti Chaturvedi, Radhakrishnan Mahalakshmi
The biogenesis of transmembrane β-barrels (outer membrane proteins, or OMPs) is an elaborate multistep orchestration of the nascent polypeptide with translocases, barrel assembly machinery, and helper chaperone proteins. Several theories exist that describe the mechanism of chaperone-assisted OMP assembly in vivo and unassisted (spontaneous) folding in vitro. Structurally, OMPs of bacterial origin possess even-numbered strands, while mitochondrial β-barrels are even- and odd-stranded. Several underlying similarities between prokaryotic and eukaryotic β-barrels and their folding machinery are known; yet, the link in their evolutionary origin is unclear...
September 21, 2017: Biochimica et Biophysica Acta
Ratanti Sarkhel, Parvathy Rajan, Ashish Kumar Gupta, Manoj Kumawat, Pranjali Agarwal, Arijit Shome, Manish Mahawar Lalsangpuii
Defending phagocyte generated oxidants is the key for survival of Salmonella Typhimurium (S. Typhimurium) inside the host. Met residues are highly prone to oxidation and convert into methionine sulfoxide (Met-SO). Methionine sulfoxide reductase (Msr) can repair Met-SO to Met thus restoring the function(s) of Met-SO containing proteins. Using pull down method we have identified several MsrA interacting proteins in the S. Typhimurium, one of them was malate synthase (MS). MS is an enzyme of glyoxylate cycle. This cycle is essential for survival of S...
September 20, 2017: Biochimica et Biophysica Acta
Martina Zandl-Lang, Elham Fanaee-Danesh, Yidan Sun, Igor Čančar, Chaitanya Chakravarthi Gali, Alexandra Kober, Nicole M Albrecher, Carmen Tam-Amersdorfer, Anika Stracke, Steffen Storck, Ahmed Saeed, Jasminka Stefulj, Claus Pietrzik, Mark R Wilson, Ingemar Björkhem, Ute Panzenboeck
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer's disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients...
September 20, 2017: Biochimica et Biophysica Acta
Chloe Rapp, Xiaoyun Bai, Reinhart A F Reithmeier
The availability of the first crystal structure of a bacterial member (SLC26Dg) of the solute carrier SLC26 family of anion transporters has allowed us to create 3-dimensional models of all 10 human members (SLC26A1-A11, A10 being a pseudogene) of these membrane proteins using the Phyre2 bioinformatic tool. The homology modeling predicted that the SLC26 human proteins, like the SLC26Dg template, all consist of 14 transmembrane segments (TM) arranged in a 7+7 inverted topology with the amino-termini of two half-helices (TM3 and 10) facing each other in the centre of the protein to create the anion-binding site, linked to a C-terminal cytosolic sulfate transporter anti-sigma factor antagonist (STAS) domain...
September 20, 2017: Biochimica et Biophysica Acta
Shuyi Wang, Xiyao Chen, Sreejayan Nair, Dongdong Sun, Xiaoming Wang, Jun Ren
Endoplasmic reticulum (ER) stress has been demonstrated to prompt various cardiovascular risks although the underlying mechanism remains elusive. Protein tyrosine phosphatase-1B (PTP1B) serves as an essential negative regulator for insulin signaling. This study examined the role of PTP1B in ER stress-induced myocardial anomalies and underlying mechanism involved with a focus on autophagy. WT and PTP1B knockout mice were subjected to the ER stress inducer tunicamycin (1mg/kg). Cardiac function was evaluated with echocardiography and an Ion-Optix MyoCam system...
September 20, 2017: Biochimica et Biophysica Acta
Joanna Panecka-Hofman, Ina Pöhner, Francesca Spyrakis, Talia Zeppelin, Flavio Di Pisa, Lucia Dello Iacono, Alessio Bonucci, Antonio Quotadamo, Alberto Venturelli, Stefano Mangani, Maria Paola Costi, Rebecca C Wade
BACKGROUND: Multi-target approaches are necessary to properly analyze or modify the function of a biochemical pathway or a protein family. An example of such a problem is the repurposing of the known human anti-cancer drugs, antifolates, as selective anti-parasitic agents. This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor β, a folate/antifolate transporter...
September 20, 2017: Biochimica et Biophysica Acta
Ana C Silva, Ildete L Ferreira, Michael R Hayden, Elisabete Ferreiro, A Cristina Rego
Huntington's disease (HD) is caused by an expansion of CAG repeats in the HTT gene, leading to expression of mutant huntingtin (mHTT) and selective striatal neuronal loss, frequently associated with mitochondrial dysfunction and decreased support of brain-derived neurotrophic factor (BDNF). New neurons derived from the subventricular zone (SVZ) are apparently not able to rescue HD pathological features. Thus, we analyzed proliferation, migration and differentiation of adult SVZ-derived neural stem/progenitor cells (NSPC) from mild (6month-old (mo)) and late (10mo) symptomatic HD YAC128 mice expressing full-length (FL)-mHTT versus age-matched wild-type (WT) mice...
September 19, 2017: Biochimica et Biophysica Acta
Daniela Valenti, Leonardo Rossi, Domenico Marzulli, Francesco Bellomo, Domenico De Rasmo, Anna Signorile, Rosa Anna Vacca
Functional and structural damages to mitochondria have been critically associated with the pathogenesis of Down syndrome (DS), a human multifactorial disease caused by trisomy of chromosome 21 and associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, we demonstrated in neural progenitor cells (NPCs) isolated from the hippocampus of Ts65Dn mice -a widely used model of DS - a severe impairment of mitochondrial bioenergetics and biogenesis and reduced NPC proliferation...
September 19, 2017: Biochimica et Biophysica Acta
Olga E Karpicheva, Vladimir V Sirenko, Nikita A Rysev, Armen O Simonyan, Danuta Borys, Joanna Moraczewska, Yurii S Borovikov
Effects of the Ala155Thr substitution in hydrophobic core of tropomyosin Tpm1.1 on conformational rearrangements of the components of the contractile system (Tpm1.1, actin and myosin heads) were studied by polarized fluorimetry technique at different stages of the actomyosin ATPase cycle. The proteins were labelled by fluorescent probes and incorporated into ghost muscle fibres. The substitution violated the blocked and closed states of thin filaments stimulating abnormal displacement of tropomyosin to the inner domains of actin, switching actin on and increasing the relative number of the myosin heads in strong-binding state...
September 19, 2017: Biochimica et Biophysica Acta
Konstantin N Belosludtsev, Natalia V Belosludtseva, Kirill S Tenkov, Nikita V Penkov, Alexey V Agafonov, Lyubov L Pavlik, Valery A Yashin, Victor N Samartsev, Mikhail V Dubinin
The effect of the antimicrobial compound triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol;) on the permeability of lecithin liposomes and rat liver mitochondria was studied. It was found that triclosan was able to increase nonspecific permeability of liposomes in a dose-dependent manner, which was detected by the release of the fluorescent probe sulforhodamine B (SRB) from vesicles. A partial release of SRB occurs instantly at the moment of triclosan addition, which is followed by a slow leakage of the dye...
September 19, 2017: Biochimica et Biophysica Acta
Marcin Broniatowski, Martyna Binczycka, Aneta Wójcik, Michał Flasiński, Paweł Wydro
High molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) are persistent organic pollutants which due to their limited biodegradability accumulate in soils where their increased presence can lead to the impoverishment of the decomposer organisms. As very hydrophobic PAHs easily penetrate cellular membranes of soil bacteria and can be incorporated therein, changing the membrane fluidity and other functions which in consequence can lead to the death of the organism. The structure and size of PAH molecule can be crucial for its membrane activity; however the correlation between PAH structure and its interaction with phospholipids have not been investigated so far...
September 19, 2017: Biochimica et Biophysica Acta
Alberto Puccini, Martin D Berger, Madiha Naseem, Ryuma Tokunaga, Francesca Battaglin, Shu Cao, Diana L Hanna, Michelle McSkane, Shivani Soni, Wu Zhang, Heinz-Josef Lenz
Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular and clinical features, which reflects the wide range of prognostic outcomes and treatment responses observed among CRC patients worldwide. Our understanding of the CRC epigenome has been largely developed over the last decade and it is now believed that among thousands of epigenetic alterations present in each tumor, a small subgroup of these may be considered as a CRC driver event. DNA methylation profiles have been the most widely studied in CRC, which includes a subset of patients with distinct molecular and clinical features now categorized as CpG island methylator phenotype (CIMP)...
September 19, 2017: Biochimica et Biophysica Acta
Alix A J Rouault, Abigail A Lee, Julien A Sebag
The Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the activity of several GPCRs involved in the control of food intake and energy expenditure. While MRAP2 was originally thought to exclusively interact with melanocortin receptors we have recently shown that it interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PKR1). In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1...
September 19, 2017: Biochimica et Biophysica Acta
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