Bioenergetics: From atomic resolution structures to cancer metabolism.
nyi L PMID: 30078645 [PubMed - in process] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 9, 2018 Category: Biochemistry Authors: Tretter L, Zimányi L Tags: Biochim Biophys Acta Source Type: research

Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis.
Abstract Psoriatic plaques tend to localize to the knees and elbows, areas that are particularly subject to mechanical stress resulting from bending and friction. Moreover, plaques often develop at sites of mechanical trauma or injury (Koebner phenomenon). Nevertheless, mechanotransduction has never been linked to psoriasis. Polycystins (polycystin-1, PC1; polycystin-2, PC2) are mechanosensitive molecules that function as key regulators of cellular mechanosensitivity and mechanotransduction. The aim of this in vitro study was to investigate the role of polycystins in the development of psoriasis. We showed that PC...
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Gargalionis AN, Malakou LS, Adamopoulos C, Piperi C, Theochari I, Nokhbehsaim M, Deschner J, Kokkalis G, Korkolopoulou P, Papadavid E, Papavassiliou AG, Basdra EK Tags: Biochim Biophys Acta Source Type: research

Live-cell imaging of early coat protein dynamics during clathrin-mediated endocytosis.
Abstract Clathrin-mediated endocytosis is an essential process that is mediated by the stepwise appearance or disappearance of many different proteins at the plasma membrane. In the budding yeast, these proteins are categorized into at least five modules, according to their spatiotemporal dynamics. Among them, the dynamics of proteins in the late coat module are well characterized, but those in the early coat module still remain unclear because of the lack of a suitable fluorescent marker with sufficient brightness to allow analysis. To examine the dynamics of early coat proteins, in this study we tagged four repr...
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Miyashita M, Kashikuma R, Nagano M, Toshima JY, Toshima J Tags: Biochim Biophys Acta Source Type: research

Ubiquitin protease Ubp8 is necessary for S. cerevisiae respiration.
Abstract Healthy mitochondria are required in cell metabolism and deregulation of underlying mechanisms is often involved in human diseases and neurological disorders. Post-translational modifications of mitochondrial proteins regulate their function and activity, accordingly, impairment of ubiquitin proteasome system affects mitochondria homeostasis and organelle dynamics. In the present study we have investigated the role of the ubiquitin protease Ubp8 in S. cerevisiae respiration. We show that Ubp8 is necessary for respiration and its expression is upregulated in glycerol respiratory medium. In addition, we sho...
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Leo M, Fanelli G, Di Vito S, Traversetti B, La Greca M, Palladino RA, Montanari A, Francisci S, Filetici P Tags: Biochim Biophys Acta Source Type: research

The role of pseudophosphatases as signaling regulators.
Abstract Pseudophosphatases are atypical members of the protein tyrosine phosphatase superfamily. Mutations within their catalytic signature motif render them catalytically inactive. Despite this lack of catalytic function, pseudophosphatases have been implicated in various diseases such as Charcot Marie-Tooth disorder, cancer, metabolic disorder, and obesity. Moreover, they have roles in various signaling networks such as spermatogenesis, apoptosis, stress response, tumorigenesis, and neurite differentiation. This review highlights the roles of pseudophosphatases as essential regulators in signaling cascades, pro...
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Hinton SD Tags: Biochim Biophys Acta Source Type: research

GAPDH with NAD+-binding site mutation competitively inhibits the wild-type and affects glucose metabolism in cancer.
CONCLUSION: Mutant-GAPDH affects the enzymatic function of cellular-GAPDH and disrupts energy metabolism. GENERAL SIGNIFICANCE: Our findings demonstrate that a minimal mutation at the NAD+-binding site is sufficient to generate a competitive but dysfunctional GAPDH, and its ectopic expression inhibits the wild-type to disrupt glycolysis. PMID: 30077773 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Kunjithapatham R, Ganapathy-Kanniappan S Tags: Biochim Biophys Acta Source Type: research

Ganglioside lipids accelerate α-synuclein amyloid formation.
Ganglioside lipids accelerate α-synuclein amyloid formation. Biochim Biophys Acta. 2018 Aug 02;: Authors: Gaspar R, Pallbo J, Weininger U, Linse S, Sparr E Abstract The deposition of α-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of α-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of α-synuclein monomers and catalyse their aggregation at mildly ac...
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Gaspar R, Pallbo J, Weininger U, Linse S, Sparr E Tags: Biochim Biophys Acta Source Type: research

Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis.
uml;rök Z, Balint BL, Papp Z, Vígh L, Bai P Abstract There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of PARP2 induced characteristic changes in the lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle. Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone, an anabolic steroid. Thus, skel...
Source: Biochimica et Biophysica Acta - August 2, 2018 Category: Biochemistry Authors: Márton J, Péter M, Balogh G, Bódi B, Vida A, Szántó M, Bojcsuk D, Jankó L, Bhattoa HP, Gombos I, Uray K, Horváth I, Török Z, Balint BL, Papp Z, Vígh L, Bai P Tags: Biochim Biophys Acta Source Type: research

Calcium, a pivotal player in photodynamic therapy?
This article is part of a Special Issue entitled: Calcium signaling in health, disease and therapy edited by Geert Bultynck and Jan Parys. PMID: 30076858 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Hoorelbeke D, Decrock E, Van Haver V, De Bock M, Leybaert L Tags: Biochim Biophys Acta Source Type: research

Myosin phosphatase: Unexpected functions of a long-known enzyme.
This article is part of a Special Issue entitled: Protein Phosphatases as Critical Regulators for Cellular Homeostasis edited by Prof. Peter Ruvolo and Dr. Veerle Janssens. PMID: 30076859 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Kiss A, Erdődi F, Lontay B Tags: Biochim Biophys Acta Source Type: research

Transcriptome analyses reveal molecular mechanisms that regulate endochondral ossification in amphibian Bufo gargarizans during metamorphosis.
CONCLUSIONS: The exquisite coordination of the 28 genes is essential for regulation of endochondral ossification during B. gargarizans metamorphosis. GENERAL SIGNIFICANCE: The present study will not only provide an invaluable genomic resource and background for further research of endochondral ossification in amphibians but will also aid in enhancing our understanding of the evolution of terrestrial vertebrates. PMID: 30076880 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Bo X, Wu M, Xiao H, Wang H Tags: Biochim Biophys Acta Source Type: research

MRGBP promotes AR-mediated transactivation of KLK3 and TMPRSS2 via acetylation of histone H2A.Z in prostate cancer cells.
This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. We first showed that MRGBP promoted growth of AR-positive prostate cancer cells. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. Furthermore, MRGBP interacted with MRG15 and TIP60 in prostate cancer cells. Androgen-stimulated AR enhanced histone H3K4me1 or H3K4me3 levels at AR binding regions. MRGBP was recruited to active gene regions through its binding with H3K4me1/3 by MRG15. Then, MRGBP promoted recr...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Ito S, Kayukawa N, Ueda T, Taniguchi H, Morioka Y, Hongo F, Ukimura O Tags: Biochim Biophys Acta Source Type: research

NASP antagonize chromatin accessibility through maintaining histone H3K9me1 in hepatocellular carcinoma.
Abstract The regulation of histone deposits mediated by multi-chaperone complexes under physiological conditions remains to be further investigated. Here, we studied the function of nuclear autoantigenic sperm protein (NASP) in the regulation of liver cancer. We found that NASP levels in liver tumors were generally higher than in normal liver tissues and NASP down-regulation inhibited liver cancer cells from forming tumors. We further analyzed cellular responses and epigenetic mechanisms of the histone H3-H4 shortage induced by NASP knockdown in liver cancer cells. The results showed that the major effects of NASP...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Kang X, Feng Y, Gan Z, Zeng S, Guo X, Chen X, Zhang Y, Wang C, Liu K, Chen X, Jiang X, Song S, Li Y, Chen S, Sun F, Mao Z, Yang X, Chang J Tags: Biochim Biophys Acta Source Type: research

Pigment epithelium derived factor regulates human Sost/Sclerostin and other osteocyte gene expression via the receptor and induction of Erk/GSK-3beta/beta-catenin signaling.
We reported that PEDF suppressed expression of Sost/Sclerostin and other osteocyte related genes in mineralizing osteoblast cultures and suggested that this could be part of the mechanisms by which PEDF regulates matrix mineralization (Li et al. J Cellular Phys. 2014). We have used a long-term differentiated mineralizing osteoblast culture (LTD) to define mechanisms by which PEDF regulates osteocyte gene expression. LTD cultures were established by culturing human osteoblasts in an osteogenic medium for 4 months followed by analysis of osteocytes related genes and encoded proteins. LTD cells synthesized Sclerostin, matri...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Li F, Cain JD, Tombran-Tink J, Niyibizi C Tags: Biochim Biophys Acta Source Type: research

Pharmacological blockade of CXCR3 by ( ±)-NBI-74330 reduces neuropathic pain and enhances opioid effectiveness - Evidence from in vivo and in vitro studies.
Pharmacological blockade of CXCR3 by (±)-NBI-74330 reduces neuropathic pain and enhances opioid effectiveness - Evidence from in vivo and in vitro studies. Biochim Biophys Acta. 2018 Aug 01;: Authors: Piotrowska A, Rojewska E, Pawlik K, Kreiner G, Ciechanowska A, Makuch W, Zychowska M, Mika J Abstract It has been suggested that CXCR3 is important for nociception. Our experiments were conducted to evaluate involvement of CXCR3 and its ligands (CXCL4, CXCL9, CXCL10, CXCL11/CCL21) in neuropathic pain. Our studies give new evidence that intrathecal administration of each CXCR3 ligand induces pain-l...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Piotrowska A, Rojewska E, Pawlik K, Kreiner G, Ciechanowska A, Makuch W, Zychowska M, Mika J Tags: Biochim Biophys Acta Source Type: research

A novel porcupine inhibitor blocks WNT pathways and attenuates cardiac hypertrophy.
Abstract WNT pathways are critically involved in the cardiac hypertrophy growth. Porcupine, an acyltransferase that specifically enables secretion of all WNT ligands, became a highly druggable target for inhibiting WNT pathways. Here we test if a novel small-molecule porcupine inhibitor CGX1321, which has entered human clinical trials as an anti-cancer agent, exerts an anti-hypertrophic effect. Four-month-old male C57 mice were used in the experiments. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in-vivo. Angiotensin-II was used to induce cardiomyocyte hypertrophy in-vitro. Card...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Jiang J, Lan C, Li L, Yang D, Xia X, Liao Q, Fu W, Chen X, An S, Wang WE, Zeng C Tags: Biochim Biophys Acta Source Type: research

Altered structure and function of fibrinogen after cleavage by Factor VII Activating Protease (FSAP).
In conclusion, altering fibrin clot properties by fibrinogenolysis is a novel function of FSAP in the vasculature, which facilitates clot lysis and may in vivo contribute to reduced fibrin deposition during thrombosis. PMID: 30076961 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Etscheid M, Subramaniam S, Lochnit G, Zabczyk M, Undas A, Lang IM, Hanschmann KM, Kanse SM Tags: Biochim Biophys Acta Source Type: research

Glucose-free/high-protein diet improves hepatomegaly and exercise intolerance in glycogen storage disease type III mice.
Abstract Glycogen disease type III (GSDIII), a rare incurable autosomal recessive disorder due to glycogen debranching enzyme deficiency, presents with liver, heart and skeletal muscle impairment, hepatomegaly and ketotic hypoglycemia. Muscle weakness usually worsens to fixed myopathy and cardiac involvement may present in about half of the patients during disease. Management relies on careful follow-up of symptoms and diet. No common agreement was reached on sugar restriction and treatment in adulthood. We administered two dietary regimens differing in their protein and carbohydrate content, high-protein (HPD) an...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Pagliarani S, Lucchiari S, Ulzi G, Ripolone M, Violano R, Fortunato F, Bordoni A, Corti S, Moggio M, Bresolin N, Comi GP Tags: Biochim Biophys Acta Source Type: research

Erratum to Residue-specific mobility changes in soluble oligomers of the prion protein define regions involved in aggregation, BBAPAP (2018) 982-988.
PMID: 30077003 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Glaves JP, Ladner-Keay CL, Bjorndahl TC, Wishart DS, Sykes BD Tags: Biochim Biophys Acta Source Type: research

Lysosomal phospholipase A2.
This article is part of a Special Issue entitled Novel functions of phospholipase A2 Guest Editors: Makoto Murakami and Gerard Lambeau. PMID: 30077006 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Shayman JA, Tesmer JJG Tags: Biochim Biophys Acta Source Type: research

Inhibition of pannexin-1 channel activity by adiponectin in podocytes: Role of acid ceramidase activation.
Abstract The pannexin-1 (Panx1) channel has been reported to mediate the release of ATP that is involved in local tissue inflammation, obesity, and many chronic degenerative diseases. It remains unknown whether Panx1 is present in podocytes and whether this channel in podocytes mediates ATP release leading to glomerular inflammation or fibrosis. To answer these questions, we first characterized the expression of Panx channels in podocytes. Among the three known pannexins, Panx1 was the most enriched in podocytes, either cultured or native in mouse glomeruli. Using a Port-a-Patch planar patch-clamp system, we recor...
Source: Biochimica et Biophysica Acta - August 1, 2018 Category: Biochemistry Authors: Li G, Zhang Q, Hong J, Ritter JK, Li PL Tags: Biochim Biophys Acta Source Type: research

PROTON GRADIENT REGULATION 5 contributes to ferredoxin-dependent cyclic phosphorylation in ruptured chloroplasts.
In this study, we revisited the classical method of monitoring cyclic phosphorylation in ruptured chloroplasts to characterize two Arabidopsis mutants: pgr5, which is defective in antimycin A-sensitive CEF, and chlororespiratory reduction 2-1 (crr2-1), which is defective in chloroplast NDH-dependent CEF. We observed a significant reduction in CEF-dependent pmf formation and consequently ATP synthesis in the pgr5 mutant, although LEF-dependent pmf formation and ATP synthesis were not impaired at photosynthetic photon flux densities below 130 μmol m-2 s-1. In contrast, the contribution of chloroplast NDH complex to ...
Source: Biochimica et Biophysica Acta - July 31, 2018 Category: Biochemistry Authors: Wang C, Takahashi H, Shikanai T Tags: Biochim Biophys Acta Source Type: research

Excitation energy transfer kinetics and efficiency in phototrophic green sulfur bacteria.
Abstract A series of spectroscopic measurements were performed on membrane fractions and detergent-solubilized complexes from the green sulfur bacterium (GSB) Chlorobaculum (Cba.) tepidum. The excitation migration through the entire GSB photosynthetic apparatus cannot be observed upon excitation of membranes in the chlorosome region at 77 K. In order to observe energy transfer from the Fenna-Matthews-Olson (FMO) protein to the reaction center (RC), FMO was directly excited at ~800 nm in transient absorption experiments. However, interpretation of the results is complicated by the spectral overlap between FMO a...
Source: Biochimica et Biophysica Acta - July 31, 2018 Category: Biochemistry Authors: Magdaong NCM, Niedzwiedzki DM, Saer RG, Goodson C, Blankenship RE Tags: Biochim Biophys Acta Source Type: research

In vitro and in vivo translational models for rare liver diseases.
Abstract A challenge in developing effective treatments is the modeling of the human disease using in vitro and in vivo systems. Animal models have played a critical role in the understanding of disease pathophysiology, target validation, and evaluation of novel therapeutic agents. However, as the success rate from entry into clinical testing to drug approval remains low, it is critical to have high quality and well-validated models reflective of the disease condition. Additional experimental models are being developed based on functional in vitro 3D tissue models such as organoids and 3D bioprinted tissues. Becau...
Source: Biochimica et Biophysica Acta - July 31, 2018 Category: Biochemistry Authors: Haugabook SJ, Ferrer M, Ottinger EA Tags: Biochim Biophys Acta Source Type: research

Applying stable carbon isotopic analysis at the natural abundance level to determine the origin of docosahexaenoic acid in the brain of the fat-1 mouse.
This study reflects the first application of CSIA to a complex multivariate model to determine the origin of brain fatty acids. PMID: 30075211 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 31, 2018 Category: Biochemistry Authors: Giuliano V, Scott Lacombe RJ, Hopperton KE, Bazinet RP Tags: Biochim Biophys Acta Source Type: research

Diverse residues of intracellular loop 5 of the Na+/H+ exchanger modulate proton sensing, expression, activity and targeting.
In this study, we characterized the structure and function of intracellular loop 5 (IL5), specifically amino acids 431-443. Mutation of eleven residues to alanine caused partial or nearly complete inhibition of transport; notably, mutation of residues L432, T433, I436, N437, R440 and K443 demonstrated these residues had critical roles in NHE1 function independent of effects on targeting or expression. The nuclear magnetic resonance (NMR) solution spectra of the IL5 peptide in a membrane mimetic sodium dodecyl sulfate solution revealed that IL5 has a stable three-dimensional structure with substantial alpha helical characte...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Wong KY, McKay R, Liu Y, Towle K, Elloumi Y, Li X, Quan S, Dutta D, Sykes BD, Fliegel L Tags: Biochim Biophys Acta Source Type: research

Cholesterol and phosphatidylethanolamine lipids exert opposite effects on membrane modulations caused by the M2 amphipathic helix.
Abstract Membrane curvature remodeling induced by amphipathic helices (AHs) is essential in many biological processes. Here we studied a model amphipathic peptide, M2AH, derived from influenza A M2. We are interested in how M2AH may promote membrane curvature by altering membrane physical properties. We used atomic force microscopy (AFM) to examine changes in membrane topographic and mechanical properties. We used electron paramagnetic resonance (EPR) spectroscopy to explore changes in lipid chain mobility and chain orientational order. We found that M2AH perturbed lipid bilayers by generating nanoscale pits. The ...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Pan J, Dalzini A, Song L Tags: Biochim Biophys Acta Source Type: research

Carbamylation promotes amyloidogenesis and induces structural changes in Tau-core hexapeptide fibrils.
CONCLUSION: Our in vitro and in silico results together suggest that carbamylation can modulate the aggregation pathway of the amyloidegenic sequences and cause structural changes in fibril assemblies GENERAL SIGNIFICANCE: Carbamylation acts as a switch, which triggers the aggregation in short amyloidogenic peptide fragments and modulate the structural changes in resulting amyloid fibrils. PMID: 30071272 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Guru KrishnaKumar V, Baweja L, Ralhan K, Gupta S Tags: Biochim Biophys Acta Source Type: research

Electrostatic control of calcineurin's intrinsically-disordered regulatory domain binding to calmodulin.
Abstract Calcineurin (CaN) is a serine/threonine phosphatase that regulates a variety of physiological and pathophysiological processes in mammalian tissue. The calcineurin (CaN) regulatory domain (RD) is responsible for regulating the enzyme's phosphatase activity, and is believed to be highly-disordered when inhibiting CaN, but undergoes a disorder-to-order transition upon diffusion-limited binding with the regulatory protein calmodulin (CaM). The prevalence of polar and charged amino acids in the regulatory domain (RD) suggests electrostatic interactions are involved in mediating calmodulin (CaM) binding, yet t...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Sun B, Cook EC, Creamer TP, Kekenes-Huskey PM Tags: Biochim Biophys Acta Source Type: research

Thrombin binding aptamer analogues containing inversion of polarity sites endowed with antiproliferative and anti-motility properties against Calu-6 cells.
CONCLUSIONS: Both TBA analogues TBA353 and TBA535 are able to form G-quadruplex structures with no anticoagulant activity. However only TBA535 is endowed with noteworthy antiproliferative and anti-motility properties against lung cancer Calu-6 cells. GENERAL SIGNIFICANCE: The switching from the anticoagulant to antiproliferative property can be obtained also in TBA derivatives not adopting the "chair-like" G-quadruplex structure typical of TBA. Furthermore, results have highlighted an unprecedented anti-cell-motility property of TBA and TBA535 reinforcing the potential of these ODNs as anticancer drugs. ...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Esposito V, Russo A, Vellecco V, Bucci M, Russo G, Mayol L, Virgilio A, Galeone A Tags: Biochim Biophys Acta Source Type: research

Novel nuclear translocation of inositol polyphosphate 4-phosphatase is associated with cell cycle, proliferation and survival.
In this study, we demonstrate for the first time that INPP4A shuttles between the cytoplasm and the nucleus. Nuclear INPP4A is enzymatically active and in dynamic equilibrium between the nucleus and cytoplasm depending on the cell cycle stage, with highest amounts detected in the nucleus during the G0/G1 phase. Moreover, nuclear INPP4A is found to have direct proliferation suppressive activity. Cells constitutively overexpressing nuclear INPP4A exhibit massive apoptosis. In human tissues as well as cell lines, lower nuclear localization of INPP4A correlate with cancerous growth. Together, our findings suggest that nuclear ...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Chaudhuri R, Khanna K, Koundinya D, Pattnaik B, Vatsa D, Agrawal A, Ghosh B Tags: Biochim Biophys Acta Source Type: research

Animal models for cystic fibrosis liver disease (CFLD).
Abstract Liver disease is a severe complication in patients with Cystic Fibrosis (CF), a genetic disease caused by mutations in the gene encoding for cystic fibrosis transmembrane conductance regulator (CFTR) channel. The sequence of events leading to CFLD is still unclear and has limited the development of more specific treatments other than the bile acid UDCA. However, in the last twenty years, several gaps have been filled, which have mainly been possible due to the availability of different animal models that mimic CF. CF mice, although they lack a spontaneous liver manifestation, have been essential to better...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Fiorotto R, Amenduni M, Mariotti V, Cadamuro M, Fabris L, Spirli C, Strazzabosco M Tags: Biochim Biophys Acta Source Type: research

Identifying lysophosphatidic acid receptor subtype 1 (LPA1) as a novel factor to modulate microglial activation and their TNF- α production by activating ERK1/2.
Identifying lysophosphatidic acid receptor subtype 1 (LPA1) as a novel factor to modulate microglial activation and their TNF-α production by activating ERK1/2. Biochim Biophys Acta. 2018 Jul 30;: Authors: Kwon JH, Gaire BP, Park SJ, Shin DY, Choi JW Abstract Microglia regulate immune responses in the brain, and their activation is key to the pathogenesis of diverse neurological diseases. Receptor-mediated lysophosphatidic acid (LPA) signaling has been known to regulate microglial biology, but it is still unclear which receptor subtypes guide the biology, particularly, microglial activation. Her...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Kwon JH, Gaire BP, Park SJ, Shin DY, Choi JW Tags: Biochim Biophys Acta Source Type: research

Quantitative NMR study of heat-induced aggregation of eye-lens crystallin proteins under crowding conditions.
y A Abstract The eye lens contains a highly concentrated, polydisperse mixture of crystallins, and a loss in transparency during cataract formation is attributed to the aggregation of these proteins. Most biochemical and biophysical studies of crystallins have been performed in diluted samples because of various physical limitations of the respective method at physiological concentrations of up to 200-400 mg/mL. We introduce a straightforward proton NMR transverse relaxometry method to quantify simultaneously proteins in the dissolved and aggregated states at these elevated concentrations, because these states s...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Camilles M, Link S, Balbach J, Saalwächter K, Krushelnitsky A Tags: Biochim Biophys Acta Source Type: research

Fine-tuning of fgf8a expression through alternative polyadenylation has a selective impact on Fgf-associated developmental processes.
;de L Abstract The formation of distinct 3'UTRs through alternative polyadenylation is a mechanism of gene expression regulation that has been implicated in many physiological and pathological processes. However, its functions in the context of vertebrate embryonic development have been largely unaddressed, in particular with a gene-specific focus. Here we show that the most abundant 3'UTR for the zebrafish fgf8a gene in the developing embryo mediates a strong translational repression, when compared to a more sparsely used alternative 3'UTR, which supports a higher translational efficiency. By inducing a shift in ...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Fernandes SF, Fior R, Pinto F, Gama-Carvalho M, Saúde L Tags: Biochim Biophys Acta Source Type: research

DNA methylation on N6-adenine in lepidopteran Bombyx mori.
Abstract Increasing knowledge of DNA methylation that occurs on the sixth position of adenine (N6-methyladenine, 6 mA) has emerged as a novel epigenetic mark in eukaryotes and plays an important role in regulating gene transcription, DNA replication and repair, transposable activities, and others. Here, we show DNA 6 mA methylation is present in Bombyx mori, a lepidopteran model insect, and identify the 6 mA methyltransferase, METTL4, and 6 mA demethylase, NMAD, which regulate the levels of 6 mA in embryogenesis and cultured cells of B. mori. Importantly, RNAi knockdown of METTL4 and NMAD not only induce...
Source: Biochimica et Biophysica Acta - July 30, 2018 Category: Biochemistry Authors: Wang X, Li Z, Zhang Q, Li B, Lu C, Li W, Cheng T, Xia Q, Zhao P Tags: Biochim Biophys Acta Source Type: research

Calcium signaling in Alzheimer's disease & therapies.
Calcium signaling in Alzheimer's disease & therapies. Biochim Biophys Acta. 2018 Jul 27;: Authors: Tong BC, Wu AJ, Li M, Cheung KH Abstract Alzheimer's disease (AD) is the most common type of dementia and is characterized by the accumulation of amyloid (Aβ) plaques and neurofibrillary tangles in the brain. Much attention has been given to develop AD treatments based on the amyloid cascade hypothesis; however, none of these drugs had good efficacy at improving cognitive functions in AD patients suggesting that Aβ might not be the disease origin. Thus, there are urgent needs for the develo...
Source: Biochimica et Biophysica Acta - July 27, 2018 Category: Biochemistry Authors: Tong BC, Wu AJ, Li M, Cheung KH Tags: Biochim Biophys Acta Source Type: research

Recent developments in cell-SELEX technology for aptamer selection.
CONCLUSIONS: The use of aptamers as therapeutic and diagnostic agents is rapidly evolving, selection techniques such as Cell-SELEX could be beneficial in identifying aptamers when the target is in its native conformation and without prior information of the cognate target, thereby bringing the aptamer development one step closer to the clinic. GENERAL SIGNIFICANCE: The information in this review can serve as a database for the design and development of futuristic oligonucleotide based diagnostics and therapeutics work. PMID: 30059712 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 27, 2018 Category: Biochemistry Authors: Kaur H Tags: Biochim Biophys Acta Source Type: research

Mitochondrial dynamics in cancer-induced cachexia.
Abstract Cancer-induced cachexia has a negative impact on quality of life and adversely affects therapeutic outcomes and survival rates. It is characterized by, often severe, loss of muscle, with or without loss of fat mass. Insight in the pathophysiology of this complex metabolic syndrome and direct treatment options are still limited, which creates a research demand. Results from recent studies point towards a significant involvement of muscle mitochondrial networks. However, data are scattered and a comprehensive overview is lacking. This paper aims to fill existing knowledge gaps by integrating published data ...
Source: Biochimica et Biophysica Acta - July 27, 2018 Category: Biochemistry Authors: van der Ende M, Grefte S, Plas R, Meijerink J, Witkamp R, Keijer J, van Norren K Tags: Biochim Biophys Acta Source Type: research

Senescence and declining reproductive potential: Insight into molecular mechanisms through testicular metabolomics.
Abstract Aging is associated with structural and functional changes in the organism that result in the declining of its functioning. Postponed parenthood has renewed the interest in age-related decline of testicular function and male fertility. Still, little is known about the molecular mechanisms associated with testicular senescence and related decline of fertility. Here we sought to elucidate the molecular basis of metabolic changes associated with testicular aging and reproductive potential using an NMR-based metabolomics approach. Testicular metabolic profiles of rats from 3 to 24 months-of-age were analyse...
Source: Biochimica et Biophysica Acta - July 27, 2018 Category: Biochemistry Authors: Jarak I, Almeida S, Carvalho RA, Sousa M, Barros A, Alves MG, Oliveira PF Tags: Biochim Biophys Acta Source Type: research

Chemosensitivity of human colon cancer cells is influenced by a p53-dependent enhancement of ceramide synthase 5 and induction of autophagy.
In conclusion, in p53wt colon cancer cells chemosensitivity against oxaliplatin or 5-FU could be enhanced by downregulation of CerS5 expression leading to reduced autophagy and mitochondrial respiration. PMID: 30059758 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 27, 2018 Category: Biochemistry Authors: Brachtendorf S, Wanger RA, Birod K, Thomas D, Trautmann S, Wegner MS, Fuhrmann DC, Brüne B, Geisslinger G, Grösch S Tags: Biochim Biophys Acta Source Type: research

Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics.
Abstract Protein phosphatase 1 (PP1) catalyzes more than half of all phosphoserine/threonine dephosphorylation reactions in mammalian cells. In vivo PP1 does not exist as a free catalytic subunit but is always associated with at least one regulatory PP1-interacting protein (PIP) to generate a large set of distinct holoenzymes. Each PP1 complex controls the dephosphorylation of only a small subset of PP1 substrates. We screened the literature for genetically engineered mouse models and identified models for all PP1 isoforms and 104 PIPs. PP1 itself and at least 49 PIPs were connected to human disease-associated phe...
Source: Biochimica et Biophysica Acta - July 26, 2018 Category: Biochemistry Authors: Ferreira M, Beullens M, Bollen M, Van Eynde A Tags: Biochim Biophys Acta Source Type: research

Energy dissipation mechanisms in the FCPb light-harvesting complex of the diatom Cyclotella meneghiniana.
ger TPJ Abstract Transient absorption spectroscopy has been applied to investigate the energy dissipation mechanisms in the nonameric fucoxanthin-chlorophyll-a,c-binding protein FCPb of the centric diatom Cyclotella meneghiniana. FCPb complexes in their unquenched state were compared with those in two types of quenching environments, namely aggregation-induced quenching by detergent removal, and clustering via incorporation into liposomes. Applying global and target analysis, in combination with a fluorescence lifetime study and annihilation calculations, we were able to resolve two quenching channels in FCPb that...
Source: Biochimica et Biophysica Acta - July 26, 2018 Category: Biochemistry Authors: Elnour HMAM, Dietzel L, Ramanan C, Büchel C, van Grondelle R, Krüger TPJ Tags: Biochim Biophys Acta Source Type: research

Molecular mechanism of Arabidopsis thaliana profilins as antifungal proteins.
CONCLUSION: PFNs may play a critical role as antifungal proteins in the Arabidopsis defense system against fungal pathogen attacks. GENERAL SIGNIFICANCE: The present study indicates that two profilin proteins, AtPFN1 and AtPFN2, can act as natural antimicrobial agents in the plant defense system. PMID: 30056100 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 26, 2018 Category: Biochemistry Authors: Park SC, Kim IR, Kim JY, Lee Y, Kim EJ, Jung JH, Jung YJ, Jang MK, Lee JR Tags: Biochim Biophys Acta Source Type: research

Epigenetic activation of PERP transcription by MKL1 contributes to ROS-induced apoptosis in skeletal muscle cells.
In conclusion, our data illustrate a novel epigenetic pathway that links PERP transcription to ROS-induced apoptosis in skeletal muscle cells. PMID: 30056131 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 26, 2018 Category: Biochemistry Authors: Li Z, Chen B, Dong W, Xu W, Song M, Fang M, Guo J, Xu Y Tags: Biochim Biophys Acta Source Type: research

Linking toxin-antitoxin systems with phenotypes: A Staphylococcus aureus viewpoint.
This article is part of a Special Issue entitled: Dynamic gene expression, edited by Prof. Patrick Viollier". PMID: 30056132 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 26, 2018 Category: Biochemistry Authors: Sierra R, Viollier P, Renzoni A Tags: Biochim Biophys Acta Source Type: research

A bidirectional crosstalk between glioblastoma and brain endothelial cells potentiates the angiogenic and proliferative signaling of sphingosine-1-phosphate in the glioblastoma microenvironment.
In this study, we sought to determine whether the crosstalk between glioblastoma cells and brain endothelial cells regulates sphingosine-1-phosphate signaling in the tumor microenvironment. Using human glioblastoma and brain endothelial cell lines, as well as primary brain endothelial cells derived from human glioblastoma, we report that glioblastoma-co-culture promotes the expression, activity, and plasma membrane enrichment of sphingosine kinase 2 in brain endothelial cells, leading to increased cellular level of sphingosine-1-phosphate, and significant potentiation of its secretion. In turn, extracellular sphingosine-1-...
Source: Biochimica et Biophysica Acta - July 26, 2018 Category: Biochemistry Authors: Hadi LA, Anelli V, Guarnaccia L, Navone S, Beretta M, Moccia F, Tringali C, Urechie V, Campanella R, Marfia G, Riboni L Tags: Biochim Biophys Acta Source Type: research

Theonellamide A, a marine-sponge-derived bicyclic peptide, binds to cholesterol in aqueous DMSO: Solution NMR-based analysis of peptide-sterol interactions using hydroxylated sterol.
In this study, we utilized 1H NMR chemical shift changes (Δδ1H) in aqueous DMSO solution to evaluate the TNM-A/sterol interaction. Because Chol does not dissolve well in this solvent, we used 25-hydroxycholesterol (25-HC) instead, which turned out to interact with membrane-bound TNM-A in a very similar way to that of Chol. We determined the dissociation constant, KD, by NMR titration experiments and measured the chemical shift changes of TNM-A induced by 25-HC binding in the DMSO solution. Significant changes were observed for several amino acid residues in a certain area of the molecule. The results from the s...
Source: Biochimica et Biophysica Acta - July 25, 2018 Category: Biochemistry Authors: Cornelio K, Espiritu RA, Hanashima S, Todokoro Y, Malabed R, Kinoshita M, Matsumori N, Murata M, Nishimura S, Kakeya H, Yoshida M, Matsunaga S Tags: Biochim Biophys Acta Source Type: research

Platelet-activating factor acetylhydrolases: An overview and update.
This article is part of a Special Issue entitled Novel functions of phospholipase A2 Guest Editors: Makoto Murakami and Gerard Lambeau. PMID: 30055287 [PubMed - as supplied by publisher] (Source: Biochimica et Biophysica Acta)
Source: Biochimica et Biophysica Acta - July 25, 2018 Category: Biochemistry Authors: Kono N, Arai H Tags: Biochim Biophys Acta Source Type: research

Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice.
Abstract Cardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ is unable to maintain the physiological CL:MLCL ratio, thus reducing CL levels and affecting mitochondrial function. BTHS is best known as a cardiac disease, but has been acknowledged as a multi-syndrome disorder, including cognitive deficits. Since reduced CL levels has also been reported in n...
Source: Biochimica et Biophysica Acta - July 25, 2018 Category: Biochemistry Authors: Cole LK, Kim JH, Amoscato AA, Tyurina YY, Bayır H, Karimi B, Siddiqui TJ, Kagan VE, Hatch GM, Kauppinen TM Tags: Biochim Biophys Acta Source Type: research