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Biochimica et Biophysica Acta

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https://www.readbyqxmd.com/read/27902935/g-quadruplex-fluorescence-sensing-by-core-extended-naphthalene-diimides
#1
Michela Zuffo, Filippo Doria, Silvia Botti, Greta Bergamaschi, Mauro Freccero
BACKGROUND: Fluorescent sensing of G-quadruplex nucleic acids (G4s) is an effective strategy to elucidate their role in vitro and in vivo. Small molecule ligands have often been exploited, producing an emission light up upon binding. Naphthalene diimides (NDIs), although potent G4 binders exhibiting red-NIR fluorophores, have only been marginally exploited, as they are usually quenched upon binding. Contrary, aggregating core-extended naphthalene diimides (cex-NDIs) proved to be effective probes...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27902929/necroptosis-in-amyotrophic-lateral-sclerosis-and-other-neurological-disorders
#2
REVIEW
Jessica R Morrice, Cheryl Y Gregory-Evans, Christopher A Shaw
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons. Cell death in ALS and in general was previously believed to exist as a dichotomy between apoptosis and necrosis. Most research investigating cell death mechanisms in ALS was conducted before the discovery of programmed necrosis thus did not use selective cell death pathway-specific markers. Recently, a new form of programmed cell death, termed "necroptosis", has been characterized and has been recently implicated in ALS as a primary mechanism driving motor neuron cell death in different forms of ALS...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27902925/targeted-inhibition-of-wrn-helicase-replication-stress-and-cancer
#3
REVIEW
Natalie Orlovetskie, Raphael Serruya, Ghada Abboud-Jarrous, Nayef Jarrous
WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN. Therefore, directed inhibition of this RecQ helicase could be beneficial to selective cancer therapy. Inhibition of WRN is feasible by the use of small-molecule inhibitors or application of RNA interference and EGS/RNase P targeting systems. Remarkably, helicase depletion leads to a severe reduction in cell viability due to mitotic catastrophe, which is triggered by replication stress induced by DNA repair failure and fork progression arrest...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27903431/differential-regulation-of-baicalin-and-scutellarin-on-ampk-and-akt-in-promoting-adipose-cell-glucose-disposal
#4
Le-Le Yang, Na Xiao, Jinfeng Liu, Kang Liu, Baolin Liu, Ping Li, Lian-Wen Qi
Baicalin and scutellarin, two flavonoid glucuronic acids isolated from Scutellaria baicalensis, exhibit beneficial effects on glucose homeostasis. Baicalin and scutellarin are similar in structure except scutellarin has an additional hydroxyl at composition C-4'. In this work, we observed that baicalin and scutellarin promoted glucose disposal in mice and in adipocytes. Baicalin selectively increased phosphorylation of AMP-activated kinase (AMPK), while scutellarin selectively enhanced Akt phosphorylation. Both of them increased AS160 phosphorylation and glucose uptake in basal condition...
November 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27899303/gambogic-acid-counteracts-mutant-p53-stability-by-inducing-autophagy
#5
Giorgia Foggetti, Laura Ottaggio, Debora Russo, Paola Monti, Paolo Degan, Gilberto Fronza, Paola Menichini
Mutant p53 (mutp53) proteins are frequently present at higher levels than the wild-type (wt) protein in tumors, and some of them can acquire oncogenic properties. Consistently, knockdown of mutp53 protein in human cancer cell lines leads to reduced cell proliferation and invasion as well as to an increased sensitivity to some anticancer drugs. Therefore, the exploitation of cellular pathways and/or molecules that promote mutp53 degradation may have a therapeutic interest. Recently, autophagy is emerging as an important pathway involved in the stability of mutp53...
November 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27894925/dihydroceramide-desaturase-inhibitors-induce-autophagy-via-dihydroceramide-dependent-and-independent-mechanisms
#6
Mireia Casasampere, Yadira F Ordóñez, Josefina Casas, Gemma Fabrias
BACKGROUND: Autophagy consists on the delivery of cytoplasmic material and organelles to lysosomes for degradation. Research on autophagy is a growing field because deciphering the basic mechanisms of autophagy is key to understanding its role in health and disease, and to paving the way to discovering novel therapeutic strategies. Studies with chemotherapeutic drugs and pharmacological tools support a role for dihydroceramides as mediators of autophagy. However, their effect on the autophagy outcome (cell survival or death) is more controversial...
November 25, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890702/foxos-in-the-impaired-heart-new-therapeutic-targets-for-cardiac-diseases
#7
REVIEW
Zhenlong Xin, Zhiqiang Ma, Shuai Jiang, Dongjin Wang, Chongxi Fan, Shouyin Di, Wei Hu, Tian Li, Junjun She, Yang Yang
Cardiac diseases have a high morbidity and mortality and affect the global population. Based on recent accumulating evidence, Forkhead box O (FOXOs) play important roles in cardiac diseases. Therefore, a summary of the current literature on the molecular mechanisms and roles of FOXOs in the heart will provide valuable information. In this review, we first briefly introduce the molecular features of FOXOs. Then, we discuss the regulation and cardiac actions of the FOXO pathways. Based on this background, we expand our discussion to the roles of FOXOs in several major cardiac diseases, such as ischemic cardiac diseases, diabetic cardiomyopathy and myocardial hypertrophy...
November 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890624/mitochondrial-camp-prevents-apoptosis-modulating-sirt3-protein-level-and-opa1-processing-in-cardiac-myoblast-cells
#8
Anna Signorile, Arcangela Santeramo, Grazia Tamma, Tommaso Pellegrino, Susanna D'Oria, Paolo Lattanzio, Domenico De Rasmo
Mitochondria, responding to a wide variety of signals, including oxidative stress, are critical in regulating apoptosis that plays a key role in the pathogenesis of a variety of cardiovascular diseases. A number of mitochondrial proteins and pathways have been found to be involved in the mitochondrial dependent apoptosis mechanism, such as optic atrophy 1 (OPA1), sirtuin 3 (Sirt3), deacetylase enzyme and cAMP signal. In the present work we report a network among OPA1, Sirt3 and cAMP in ROS-dependent apoptosis...
November 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890580/lipid-free-apoa-i-structure-origins-of-model-diversity
#9
REVIEW
Michael N Oda
Apolipoprotein A-I (apoA-I) is a prominent member of the exchangeable apolipoprotein class of proteins, capable of transitioning between lipid-bound and lipid-free states. It is the primary structural and functional protein of high density lipoprotein (HDL). Lipid-free apoA-I is critical to de novo HDL formation as it is the preferred substrate of the lipid transporter, ATP Binding Cassette Transporter A1 (ABCA1) Remaley et al. (2001) [1]. Lipid-free apoA-I is an important element in reverse cholesterol transport and comprehension of its structure is a core issue in our understanding of cholesterol metabolism...
November 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890680/the-putative-role-of-maldi-msi-in-the-study-of-membranous-nephropathy
#10
Andrew Smith, Vincenzo L'Imperio, Elena Ajello, Franco Ferrario, Niccolò Mosele, Martina Stella, Manuel Galli, Clizia Chinello, Federico Pieruzzi, Goce Spasovski, Fabio Pagni, Fulvio Magni
Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that represents the leading cause of nephrotic syndrome in adults and is one of the most frequent glomerulopathies worldwide. This glomerular disease can manifest as primary (idiopathic) or secondary and this distinction is crucial when choosing the most appropriate management of patients. In secondary cases, the best strategy consists in treating the underlying disease whereas in primary forms, the possible identification of confirmatory markers of the idiopathic etiology underlining the process is requested by clinicians...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890679/evaluation-of-non-supervised-maldi-mass-spectrometry-imaging-combined-with-microproteomics-for-glioma-grade-iii-classification
#11
Emilie Le Rhun, Marie Duhamel, Maxence Wisztorski, Jean-Pascal Gimeno, Fahed Zairi, Fabienne Escande, Nicolas Reyns, Firas Kobeissy, Claude-Alain Maurage, Michel Salzet, Isabelle Fournier
An integrated diagnosis using molecular features is recommended in the 2016 World Health Organization (WHO) classification. Our aim was to explore non-targeted molecular classification using MALDI mass spectrometry imaging (MALDI MSI) associated to microproteomics in order to classify anaplastic glioma by integration of clinical data. We used fresh-frozen tissue sections to perform MALDI MSI of proteins based on their digestion peptides after in-situ trypsin digestion of the tissue sections and matrix deposition by micro-spraying...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890678/hot-spot-mapping-of-protein-surfaces-with-tempol-bovine-pancreatic-rnase-a-as-a-model-system
#12
Neri Niccolai, Edoardo Morandi, Simone Gardini, Valentino Costabile, Roberta Spadaccini, Orlando Crescenzi, Delia Picone, Ottavia Spiga, Andrea Bernini
TEMPOL spin-label has been used to identify surface exposure of protein nuclei from NMR analysis of the induced paramagnetic relaxation enhancements (PRE). The absence of linear dependence between atom depths and observed PRE reveals that specific mechanisms drive the approach of the paramagnet to the protein surface. RNase A represents a unique protein system to explore the fine details of the information offered by TEMPOL induced PRE, due to the abundance of previous results, obtained in solution and in the crystal, dealing with surface dynamics behavior of this protein...
November 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890529/mass-spectrometry-analysis-shows-the-biosynthetic-pathways-supported-by-pyruvate-carboxylase-in-highly-invasive-breast-cancer-cells
#13
Phatchariya Phannasil, Israr-Ul H Ansari, Mahmoud El Azzouny, Melissa J Longacre, Khanti Rattanapornsompong, Charles F Burant, Sarawut Jitrapakdee, Michael J MacDonald
We recently showed that the anaplerotic enzyme pyruvate carboxylase (PC) is up-regulated in human breast cancer tissue and its expression is correlated with the late stages of breast cancer and tumor size [Phannasil et al., PloS One 10, e0129848, 2015]. In the current study we showed that PC enzyme activity is much higher in the highly invasive breast cancer cell line MDA-MB-231 than in less invasive breast cancer cell lines. We generated multiple stable PC knockdown cell lines from the MDA-MB-231 cell line and used mass spectrometry with (13)C6-glucose and (13)C5-glutamine to discern the pathways that use PC in support of cell growth...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890528/pathological-concentration-of-zinc-dramatically-accelerates-abnormal-aggregation-of-full-length-human-tau-and-thereby-significantly-increases-tau-toxicity-in-neuronal-cells
#14
Ji-Ying Hu, De-Lin Zhang, Xiao-Ling Liu, Xue-Shou Li, Xiao-Qing Cheng, Jie Chen, Hai-Ning Du, Yi Liang
A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn(2+) on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn(2+) dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27889440/non-heat-shock-responsive-roles-of-hsf1-in-candida-albicans-are-essential-under-iron-deprivation-and-drug-defense
#15
Remya Nair, Mohd Shariq, Sanjiveeni Dhamgaye, Chinmay K Mukhopadhyay, Shamim Shaikh, Rajendra Prasad
Recently, we have reported that the conditional mutant of the heat shock factor-1 (HSF1) in Candida albicans displays enhanced susceptibility not only towards a plant alkaloid, berberine, but also to diverse antifungal drugs. The present study attempts to identify additional phenotypes highlighting the non-heat shock responsive roles of HSF1 that could be correlated with the enhanced drug susceptibility. We uncover an intricate relationship between cellular iron and HSF1 mediated drug susceptibility of C. albicans...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27889304/distinct-membrane-properties-are-differentially-influenced-by-cardiolipin-content-and-acyl-chain-composition-in-biomimetic-membranes
#16
Edward Ross Pennington, Amy Fix, E Madison Sullivan, David A Brown, Anthony Kennedy, Saame Raza Shaikh
Cardiolipin (CL) has a critical role in maintaining mitochondrial inner membrane structure. In several conditions such as heart failure and aging, there is loss of CL content and remodeling of CL acyl chains, which are hypothesized to impair mitochondrial inner membrane biophysical organization. Therefore, this study discriminated how CL content and acyl chain composition influenced select properties of simple and complex mitochondrial mimicking model membranes. We focused on monolayer excess area/molecule (a measure of lipid miscibility), bilayer phase transitions, and microdomain organization...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27889303/pgla-h-tandem-repeat-peptides-active-against-multidrug-resistant-clinical-bacterial-isolates
#17
Tomislav Rončević, Goran Gajski, Nada Ilić, Ivana Goić-Barišić, Marija Tonkić, Larisa Zoranić, Juraj Simunić, Monica Benincasa, Marijana Mijaković, Alessandro Tossi, Davor Juretić
Antimicrobial peptides (AMPs) are promising candidates for new antibiotic classes but often display an unacceptably high toxicity towards human cells. A naturally produced C-terminal fragment of PGLa, named PGLa-H, has been reported to have a very low haemolytic activity while maintaining a moderate antibacterial activity. A sequential tandem repeat of this fragment, diPGLa-H, was designed, as well as an analogue with a Val to Gly substitution at a key position. These peptides showed markedly improved in vitro bacteriostatic and bactericidal activity against both reference strains and multidrug resistant clinical isolates of Gram-negative and Gram-positive pathogens, with generally low toxicity for human cells as assessed by haemolysis, cell viability, and DNA damage assays...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27888147/pathway-analysis-of-complex-diseases-for-gwas-extending-to-consider-rare-variants-multi-omics-and-interactions
#18
REVIEW
Patrick Y P Kao, Kim Hung Leung, Lawrence W C Chan, Shea Ping Yip, Maurice K H Yap
BACKGROUND: Genome-wide association studies (GWAS) is a major method for studying the genetics of complex diseases. Finding all sequence variants to explain fully the aetiology of a disease is difficult because of their small effect sizes. To better explain disease mechanisms, pathway analysis is used to consolidate the effects of multiple variants, and hence increase the power of the study. While pathway analysis has previously been performed within GWAS only, it can now be extended to examining rare variants, other "-omics" and interaction data...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27888146/a-rhodium-iii-based-inhibitor-of-autotaxin-with-antiproliferative-activity
#19
Tian-Shu Kang, Wanhe Wang, Hai-Jing Zhong, Jia-Xin Liang, Chung-Nga Ko, Jin-Jian Lu, Xiu-Ping Chen, Dik-Lung Ma, Chung-Hang Leung
BACKGROUND: Cancer of the skin is by far the most common of all cancers. Melanoma accounts for only about 1% of skin cancers but causes a large majority of skin cancer deaths. Autotaxin (ATX), also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), regulates physiological and pathological functions of lysophosphatidic acid (LPA), and is thus an important therapeutic target. METHODS: We synthesized ten metal-based complexes and a novel cyclometalated rhodium(III) complex 1 was identified as an ATX enzymatic inhibitor using multiple methods, including ATX enzymatic assay, thermal shift assay, western immunoblotting and so on...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27888145/critical-role-of-hnrnp-a1-in-activating-kras-transcription-in-pancreatic-cancer-cells-a-molecular-mechanism-involving-g4-dna
#20
REVIEW
Susanna Cogoi, Valentina Rapozzi, Sabina Cauci, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. Its crucial role in the tumourigenesis of pancreatic ductal adenocarcinoma (PDAC) has been widely demonstrated. As this deadly cancer does not sufficiently respond to conventional chemotherapies, it is important to increase our knowledge of pancreatic cancer biology, in particular how oncogenic KRAS is regulated. The promoter of KRAS contains a GA-element composed of runs of guanines that fold into a G4 structure. This unusual DNA conformation is recognized by several nuclear proteins, including MAZ and hnRNP A1...
November 22, 2016: Biochimica et Biophysica Acta
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