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Biological Chemistry

Guo-Qing Song, Yi Zhao
Down-regulation of meningioma-associated protein (MAC30) gene has been found many solid cancers. This study was carried out to determine the roles and the mechanisms of MAC30 in breast cancer. We used our own data and public database to analyze the MAC30 mRNA and protein levels in breast cancer tissues. In addition, we established MAC30 knockdown breast cancer cells using MAC30 siRNA. The roles of MAC30 were detected by using Soft agar assay, annexinV-FITC/PI double staining, and Transwell assay. Western blotting was used to analyze the potential mechanism(s) of MAC30 in these cells...
July 1, 2018: Biological Chemistry
Ek R Adhikari, Vladimir Samara, Sylwia Ptasinska
It is now well established that plasma-induced reactive species are key agents involved in many biochemical reactions. This work reports on the formation of plasma reactive species in an acidified ferrous sulfate (Fricke) solution interacting with an atmospheric pressure plasma jet (APPJ). A yield of ferric (Fe3+) ions measured using in situ absorption spectroscopy was attributed to the formation of plasma reactive species provided and/or originated in the solution. The results indicated that the number of reactive species formed was proportional to plasma frequency and voltage...
July 1, 2018: Biological Chemistry
Judith Bezgovsek, Erich Gulbins, Sarah-Kim Friedrich, Karl S Lang, Vikas Duhan
In this review, we summarize the mechanisms by which sphingolipids modulate virus multiplication and the host innate immune response, using a number of host-virus systems as illustrative models. Sphingolipids exert diverse functions, both at the level of the viral life cycle and in the regulation of antiviral immune responses. Sphingolipids may influence viral replication in three ways: by serving as (co)receptors during viral entry, by modulating virus replication, and by shaping the antiviral immune response...
July 1, 2018: Biological Chemistry
Shihui Guo, Peter Briza, Viktor Magdolen, Hans Brandstetter, Peter Goettig
Human kallikrein-related peptidases 3, 4, 11, and KLK2, the activator of KLK3/PSA, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process. Notably, these KLKs are upregulated in prostate cancer and are used as clinical biomarkers or have been proposed as therapeutic targets. However, this potential awaits a detailed characterization of these proteases. In order to study glycosylated prostatic KLKs resembling the natural proteases, we used Leishmania (LEXSY) and HEK293 cells for secretory expression...
July 1, 2018: Biological Chemistry
Andreas Porodko, Ana Cirnski, Drazen Petrov, Teresa Raab, Melanie Paireder, Bettina Mayer, Daniel Maresch, Lisa Nika, Martin L Biniossek, Patrick Gallois, Oliver Schilling, Chris Oostenbrink, Marko Novinec, Lukas Mach
The genome of the model plant Arabidopsis thaliana encodes three paralogues of the papain-like cysteine proteinase cathepsin B (AtCathB1, AtCathB2 and AtCathB3), whose individual functions are still largely unknown. Here we show that a mutated splice site causes severe truncations of the AtCathB1 polypeptide, rendering it catalytically incompetent. By contrast, AtCathB2 and AtCathB3 are effective proteases which display comparable hydrolytic properties and share most of their substrate specificities. Site-directed mutagenesis experiments demonstrated that a single amino acid substitution (Gly336→Glu) is sufficient to confer AtCathB2 with the capacity to tolerate arginine in its specificity-determining S2 subsite, which is otherwise a hallmark of AtCathB3-mediated cleavages...
June 27, 2018: Biological Chemistry
Aysel Aslanli, Ilya Lyagin, Elena Efremenko
N-acyl homoserine lactones (AHLs) are quorum sensing (QS) signal molecules used by most Gram-negative pathogenic bacteria. In this article the lactonase activity of the preparations based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) towards AHLs was studied. Initially, three of the most interesting β-lactam antibiotics were selected from seven that were trialed during molecular docking to His6-OPH. Combinations of antibiotics (meropenem, imipenem, ceftriaxone) and His6-OPH taken in the native form or in the form of non-covalent enzyme-polyelectrolyte complexes (EPCs) with poly(glutamic acid) or poly(aspartic acid) were obtained and investigated...
June 19, 2018: Biological Chemistry
Gavin Morris, Stoyan Stoychev, Previn Naicker, Heini W Dirr, Sylvia Fanucchi
Forkhead box (FOX) proteins are a ubiquitously expressed family of transcription factors that regulate the development and differentiation of a wide range of tissues in animals. The FOXP subfamily members are the only known FOX proteins capable of forming domain-swapped forkhead domain (FHD) dimers. This is proposed to be due to an evolutionary mutation (P539A) that lies in the FHD hinge loop, a key region thought to fine-tune DNA sequence specificity in the FOX transcription factors. Considering the importance of the hinge loop in both the dimerisation mechanism of the FOXP FHD and its role in tuning DNA binding, a detailed investigation into the implications of mutations within this region could provide important insight into the evolution of the FOX family...
June 7, 2018: Biological Chemistry
Katarina Hočevar, Jan Potempa, Boris Turk
Gingipains are extracellular cysteine proteases of the oral pathogen Porphyromonas gingivalis and its most potent virulence factors. They can degrade a great variety of host proteins, thereby helping the bacterium to evade the host immune response, deregulate signaling pathways, trigger anoikis and, finally, cause tissue destruction. Host cell-surface proteins targeted by gingipains are the main focus of this review and span three groups of substrates: immune-regulatory proteins, signaling pathways regulators and adhesion molecules...
June 1, 2018: Biological Chemistry
Jianfa Jiang, Kenan Yu, Zhaoying Jiang, Min Xue
Endometriosis (EMs) is a chronic inflammatory condition. Interleukin (IL)-37 is a member of the IL-1 family and an anti-inflammatory cytokine. This study aimed to evaluate the possible role of IL-37 in the EMs pathogenesis. We investigated the in vivo effect of IL-37 on EMs by injection with recombinant human IL-37 (rhIL-37) into EMs mice. Furthermore, we evaluated the in-vitro effects of IL-37 on proliferation, adhesion, migration, and invasiveness of endometrial stromal cells (ESCs), and explored whether Wnt/β-catenin and mitogen-activated protein kinase (MAPK) pathways were involved in this process...
June 1, 2018: Biological Chemistry
Kristina Henz, Aoula Al-Zebeeby, Marion Basoglu, Simone Fulda, Gerald M Cohen, Shankar Varadarajan, Meike Vogler
Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Specifically, the selective BH3-mimetics ABT-199, A-1331852 and S63845, which target BCL-2, BCL-XL and MCL-1, respectively, induce comparable ultrastructural changes including mitochondrial swelling, a decrease of mitochondrial matrix density and severe loss of cristae structure...
June 1, 2018: Biological Chemistry
Alibek Abdrakhmanov, Andrey V Kulikov, Ekaterina A Luchkina, Boris Zhivotovsky, Vladimir Gogvadze
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. The removal of malfunctioning or damaged mitochondria is essential for normal cellular physiology and tissue development. Stimulation of mitochondrial permeabilization and release of proapoptotic factors from the intermembrane space is an essential step in triggering the mitochondrial pathway of cell death. In this study, we analyzed the extent to which mitophagy interferes with cell death, attenuating the efficiency of cancer therapy...
June 1, 2018: Biological Chemistry
Monica Vara-Perez, Hannelore Maes, Sarah Van Dingenen, Patrizia Agostinis
Aerobic glycolysis (Warburg effect) is used by cancer cells to fuel tumor growth. Interestingly, metastatic melanoma cells rely on glutaminolysis rather than aerobic glycolysis for their bioenergetic needs through the tricarboxylic acid cycle. Here, we compared the effects of glucose or glutamine on melanoma cell proliferation, migration and oxidative phosphorylation in vitro. We found that glutamine-driven melanoma cell's aggressive traits positively correlated with increased expression of HIF1α and its pro-autophagic target BNIP3...
June 1, 2018: Biological Chemistry
Alexander Simonis, Alexandra Schubert-Unkmeir
Acid sphingomyelinase (ASM) is a key enzyme in sphingolipid metabolism that converts sphingomyelin to ceramide, thereby modulating membrane structures and signal transduction. Bacterial pathogens can manipulate ASM activity and function, and use host sphingolipids during multiple steps of their infection process. An increase in ceramides upon infection results in the formation of ceramide-enriched membrane platforms that serve to cluster receptor molecules and organize intracellular signaling molecules, thus facilitating bacterial uptake...
June 1, 2018: Biological Chemistry
Yuqing Wu, Erich Gulbins, Heike Grassmé
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the deadliest and most important infectious diseases worldwide. The sphingomyelinase/ceramide system, which has been shown several times to be a crucial factor in the internalization, processing, and killing of diverse pathogens, also modulates the pro-inflammatory response and the state of mycobacteria in macrophages. Both acid and neutral sphingomyelinases are important in this activity. However, studies of the role of sphingomyelinases in TB are still at an early stage...
June 1, 2018: Biological Chemistry
Ling-Li Zhang, Lian-Feng Zhang, Yun-Bo Shi
The paxillin and M2 macrophage are all involved in cell proliferation and tumor progression, and this study aims to explore the interaction between them in colon cancer and the role of paxillin in cancer progression. Expression of mRNAs and proteins was determined by qRTPCR and western blot, separately. Endogenous expression of genes was modulated by recombinant plasmids and cell transfection. The levels of cytokines were determined by ELISA. The cell viability, invasion and migration were detected by MTT assay, transwell assay and wound-healing cell migration assay, respectively...
June 1, 2018: Biological Chemistry
Rahil Eftekhari, Stacy G de Lima, Yu Liu, Koichiro Mihara, Mahmoud Saifeddine, Farshid Noorbakhsh, Isobel A Scarisbrick, Morley D Hollenberg
We propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinaseactivated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work shows that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes...
June 1, 2018: Biological Chemistry
Anna L Lang, Juliane I Beier
Occupational and environmental exposures to industrial chemicals are known to cause hepatotoxicity and liver injury, in humans and in animal models. Historically, research has focused on severe acute liver injury (e.g., fulminant liver failure) or endstage diseases (e.g., cirrhosis and HCC). However, it has become recently recognized that toxicants can cause more subtle changes to the liver. For example, toxicant-associated steatohepatitis (TASH), characterized by hepatic steatosis, and inflammation, was recently recognized in an occupational cohort exposed to vinyl chloride...
June 1, 2018: Biological Chemistry
Gerhild van Echten-Deckert, Shah Alam
In mammals, the brain exhibits the highest lipid content in the body next to adipose tissue. Complex sphingolipids are characteristic compounds of neuronal membranes. Vital neural functions including information flux and transduction occur along these membranes. It is therefore not surprising that neuronal function and survival is dependent on the metabolism of these lipids. Autophagy is a critical factor for the survival of post-mitotic neurons. On one hand it fulfils homeostatic and waste-recycling functions and on the other hand it constitutes an effective strategy to eliminate harmful proteins that cause neuronal death...
June 1, 2018: Biological Chemistry
Manuela D'Eletto, Federica Rossin, Olga Fedorova, Maria Grazia Farrace, Mauro Piacentini
The maintenance of protein homeostasis (proteostasis) is a fundamental aspect of cell physiology that is essential for the survival of organisms under a variety of environmental and/or intracellular stress conditions. Acute and/or persistent stress exceeding the capacity of the intracellular homeostatic systems results in protein aggregation and/or damaged organelles that leads to pathological cellular states often resulting in cell death. These events are continuously suppressed by a complex macromolecular machinery that uses different intracellular pathways to maintain the proteome integrity in the various subcellular compartments ensuring a healthy cellular life span...
June 1, 2018: Biological Chemistry
Unekwu M Yakubu, Kevin A Morano
Cellular protein homeostasis (proteostasis) is maintained by a broad network of proteins involved in synthesis, folding, triage, repair and degradation. Chief among these are molecular chaperones and their cofactors that act as powerful protein remodelers. The growing realization that many human pathologies are fundamentally diseases of protein misfolding (proteopathies) has generated interest in understanding how the proteostasis network impacts onset and progression of these diseases. In this minireview, we highlight recent progress in understanding the enigmatic Hsp110 class of heat shock protein that acts as both a potent nucleotide exchange factor to regulate activity of the foldase Hsp70, and as a passive chaperone capable of recognizing and binding cellular substrates on its own, and its integration into the proteostasis network...
June 1, 2018: Biological Chemistry
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