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https://www.readbyqxmd.com/read/29786671/mechanisms-of-action-and-cell-death-associated-with-clostridium-perfringens-toxins
#1
REVIEW
Mauricio A Navarro, Bruce A McClane, Francisco A Uzal
Clostridium perfringens uses its large arsenal of protein toxins to produce histotoxic, neurologic and intestinal infections in humans and animals. The major toxins involved in diseases are alpha (CPA), beta (CPB), epsilon (ETX), iota (ITX), enterotoxin (CPE), and necrotic B-like (NetB) toxins. CPA is the main virulence factor involved in gas gangrene in humans, whereas its role in animal diseases is limited and controversial. CPB is responsible for necrotizing enteritis and enterotoxemia, mostly in neonatal individuals of many animal species, including humans...
May 22, 2018: Toxins
https://www.readbyqxmd.com/read/29786613/biophysics-of-membrane-curvature-remodeling-at-molecular-and-mesoscopic-lengthscales
#2
Natesan Ramakrishnan, Ryan P Bradley, Richard W Tourdot, Ravi Radhakrishnan
At the micron scale, where cell organelles display an amazing complexity in their shape and organization, the physical properties of a biological membrane can be better-understood using continuum models subject to thermal (stochastic) undulations. Yet, the chief orchestrators of these complex and intriguing shapes are a specialized class of membrane associating often peripheral proteins called curvature remodeling proteins (CRPs) that operate at the molecular level through specific protein-lipid interactions...
May 22, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29786451/annexin-a2-is-a-robo4-ligand-that-modulates-arf6-activation-associated-cerebral-trans-endothelial-permeability
#3
Wenlu Li, Zhigang Chen, Jing Yuan, Zhanyang Yu, Chongjie Cheng, Qiuchen Zhao, Lena Huang, Katherine A Hajjar, Zhong Chen, Eng H Lo, Haibin Dai, Xiaoying Wang
Blood-brain barrier (BBB) disruption in neurological disorders remains an intractable problem with limited therapeutic options. Here, we investigate whether the endothelial cell membrane protein annexin A2 (ANXA2) may play a role in reducing trans-endothelial permeability and maintaining cerebrovascular integrity after injury. Compared with wild-type mice, the expression of cerebral endothelial junctional proteins was reduced in E15.5 and adult ANXA2 knockout mice, along with increased leakage of small molecule tracers...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29786141/an-inhibitory-antibody-targeting-carbonic-anhydrase-xii-abrogates-chemoresistance-and-significantly-reduces-lung-metastases-in-an-orthotopic-breast-cancer-model-in-vivo
#4
Bettina von Neubeck, Gabor Gondi, Chiara Riganti, Chenchen Pan, Arnaldo Parra Damas, Hagen Scherb, Ali Ertürk, Reinhard Zeidler
Carbonic Anhydrase XII (CAXII) is a membrane-tethered ectoenzyme involved in intracellular pH regulation and overexpressed across various types of human cancer. Because CAXII inhibition shows antitumour activity in vitro, it is thought that the enzyme is mandatory for maximum tumour growth, above all under hypoxic conditions. Recently, it has been shown that CAXII is co-expressed along with the P-glycoprotein (P-GP) on many tumour cells and that both proteins physically interact. Of interest, blocking CAXII activity also decreases P-GP activity in cancer cells both in vitro and in vivo...
May 22, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29784975/a-unique-cytoplasmic-atpase-complex-defines-the-legionella-pneumophila-type-iv-secretion-channel
#5
David Chetrit, Bo Hu, Peter J Christie, Craig R Roy, Jun Liu
Type IV secretion systems (T4SSs) are complex machines used by bacteria to deliver protein and DNA complexes into target host cells1-5 . Conserved ATPases are essential for T4SS function, but how they coordinate their activities to promote substrate transfer remains poorly understood. Here, we show that the DotB ATPase associates with the Dot-Icm T4SS at the Legionella cell pole through interactions with the DotO ATPase. The structure of the Dot-Icm apparatus was solved in situ by cryo-electron tomography at 3...
May 21, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29784973/significance-of-prohibitin-domain-family-in-tumorigenesis-and-its-implication-in-cancer-diagnosis-and-treatment
#6
Jie Yang, Bin Li, Qing-Yu He
Prohibitin (PHB) was originally isolated and characterized as an anti-proliferative gene in rat liver. The evolutionarily conserved PHB gene encodes two human protein isoforms with molecular weights of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues...
May 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29784815/virb8-homolog-trae-from-plasmid-pkm101-forms-a-hexameric-ring-structure-and-interacts-with-the-virb6-homolog-trad
#7
Bastien Casu, Charline Mary, Aleksandr Sverzhinsky, Aurélien Fouillen, Antonio Nanci, Christian Baron
Type IV secretion systems (T4SSs) are multiprotein assemblies that translocate macromolecules across the cell envelope of bacteria. X-ray crystallographic and electron microscopy (EM) analyses have increasingly provided structural information on individual T4SS components and on the entire complex. As of now, relatively little information has been available on the exact localization of the inner membrane-bound T4SS components, notably the mostly periplasmic VirB8 protein and the very hydrophobic VirB6 protein...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29783958/sanguinarine-triggers-intrinsic-apoptosis-to-suppress-colorectal-cancer-growth-through-disassociation-between-strap-and-melk
#8
Xianling Gong, Zhihong Chen, Qinrui Han, Chunhui Chen, Linlin Jing, Yawei Liu, Liang Zhao, Xueqing Yao, Xuegang Sun
BACKGROUND: Previous studies showed sanguinarine induced apoptosis in CRC cells but did not define the underlying mechanisms. The purpose of this work was to determine the in vivo and in vitro effects of sanguinarine on CRC tumors and to elucidate the mechanism in regulating the intrinsic apoptosis. METHODS: Cell viability of CRC cell lines treated with sanguinarine was measured by MTT assay. Apoptotic cells stained with Annexin V and 7-AAD were detected by flow cytometry...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29783784/cyclodextrins-assessing-the-impact-of-cavity-size-occupancy-and-substitutions-on-cytotoxicity-and-cholesterol-homeostasis
#9
Lajos Szente, Ashutosh Singhal, Andras Domokos, Byeongwoon Song
Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. The potency of CD-mediated cytotoxicity was in the order of β-CDs, α-CDs, and γ-CDs...
May 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29783744/interplay-between-er-ca-2-binding-proteins-stim1-and-stim2-is-required-for-store-operated-ca-2-entry
#10
Heather A Nelson, Colin A Leech, Richard F Kopp, Michael W Roe
Store-operated calcium entry (SOCE), a fundamentally important homeostatic and Ca2+ signaling pathway in many types of cells, is activated by the direct interaction of stromal interaction molecule 1 (STIM1), an endoplasmic reticulum (ER) Ca2+ -binding protein, with Ca2+ -selective Orai1 channels localized in the plasma membrane. While much is known about the regulation of SOCE by STIM1, the role of stromal interaction molecule 2 (STIM2) in SOCE remains incompletely understood. Here, using clustered regularly interspaced short palindromic repeats -CRISPR associated protein 9 (CRISPR-Cas9) genomic editing and molecular imaging, we investigated the function of STIM2 in NIH 3T3 fibroblast and αT3 cell SOCE...
May 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783198/toxicity-assessment-of-metal-oxide-nano-pollutants-on-tomato-solanum-lycopersicon-a-study-on-growth-dynamics-and-plant-cell-death
#11
Bilal Ahmed, Mohammad Saghir Khan, Javed Musarrat
The present study for the first time demonstrated the interactions of metal oxide (MO) nano-pollutants (CuO and Al2 O3 -NPs) with tissues and cellular DNA of tomato plants grown in soil sand: silt: clay (667:190:143) and Hoagland-hydroponic system and assessed the hazardous effects of NPs on cell physiology and biochemistry. Results of SEM equipped with EDX revealed attachment of variably shaped CuO-NPs (18 nm) and Al2 O3 -NPs (21 nm) on roots, and internalization followed by translocation in plants by ICP-MS and TEM...
May 18, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29783183/identification-of-novel-phosphatidic-acid-binding-domain-on-sphingosine-kinase-1-of-arabidopsis-thaliana
#12
Shatakshi Pandit, Vikram Dalal, Girish Mishra
Phosphatidic acid (PA) is an important lipid signaling molecule which interacts with Arabidopsis thaliana Sphingosine kinase1 (AtSPHK1) during several abiotic stresses particularly drought stress as a result of Abscisic acid (ABA) signaling in guard cells. PA molecules respond by generating lipid signal and/or by binding and translocating target proteins to membrane. However, site of interaction and role of PA binding to AtSPHK1 is not clear yet. Owing to the importance of AtSPHK1 during stress signaling it is imperative to decipher the site of PA interaction with AtSPHK1...
May 8, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29782904/intracellular-s1p-levels-dictates-fate-of-different-regions-of-the-hippocampus-following-transient-global-cerebral-ischemia
#13
Sherif Rashad, Kuniyasu Niizuma, Daisuke Saigusa, Xiaobo Han, Mika Sato-Maeda, Ritsumi Saito, Akira Uruno, Miki Fujimura, Shuntaro Ikawa, Masayuki Yamamoto, Teiji Tominaga
Sphingosine-1-phosphate (S1P) is a sphingolipid molecule produced by the action of sphingosine kinases (SphK) on sphingosine. It possesses various intracellular functions through its interactions with intracellular proteins or via its action on five G-protein-coupled cell membrane receptors. Following transient global cerebral ischaemia (tGCI), only the CA1 subregion of the hippocampus undergoes apoptosis. In this study, we evaluated S1P levels and S1P processing enzyme expression in different hippocampal areas following tGCI in rats...
May 18, 2018: Neuroscience
https://www.readbyqxmd.com/read/29780159/modulation-of-store-operated-calcium-entry-and-nascent-adhesion-by-p21-activated-kinase-1
#14
In-Sook Jeon, Hye-Ryun Kim, Eun-Young Shin, Eung-Gook Kim, Heon-Seok Han, Jin-Tae Hong, Hak-Kyo Lee, Ki-Duk Song, Joong-Kook Choi
Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE)...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29779329/-mechanisms-of-recombinant-adenovirus-mediated-sd-ha-fusion-protein-proliferation-inhibition-and-induced-apoptosis-of-k562-cells
#15
Y Huang, P Zhang, L Du, M Gui, W L Feng, Z Peng
Objective: To investigate whether fusion protein SD-HA could regulate its downstream signaling molecule activity by competing with the phospho-BCR-ABL Y177 site, and its mechanisms to inhibit proliferation and induce apoptosis of K562 cells. Methods: Co-immunoprecipitation interaction technology analysis of fusion protein SD-HA functioned by potently binding to the phospho-BCR-ABL Y177 site, Ras, MAPK and Akt activities were observed in the Ad5F35-SD-HA-treated cells. Western blot analyses of SD-HA fusion protein on cell membrane receptor pathway to death cascade caspase-8, caspase-3 and PRAP were performed...
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29779049/biochemical-and-functional-interplay-between-ion-channels-and-the-components-of-the-dystrophin-associated-glycoprotein-complex
#16
REVIEW
Margarita Leyva-Leyva, Alejandro Sandoval, Ricardo Felix, Ricardo González-Ramírez
Dystrophin is a cytoskeleton-linked membrane protein that binds to a larger multiprotein assembly called the dystrophin-associated glycoprotein complex (DGC). The deficiency of dystrophin or the components of the DGC results in the loss of connection between the cytoskeleton and the extracellular matrix with significant pathophysiological implications in skeletal and cardiac muscle as well as in the nervous system. Although the DGC plays an important role in maintaining membrane stability, it can also be considered as a versatile and flexible molecular complex that contribute to the cellular organization and dynamics of a variety of proteins at specific locations in the plasma membrane...
May 19, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29778978/tough-love-accommodating-intracellular-bacteria-through-directed-secretion-of-antimicrobial-peptides-during-the-nitrogen-fixing-symbiosis
#17
REVIEW
Christina Stonoha-Arther, Dong Wang
The symbiosis formed by nitrogen-fixing bacteria with plant hosts mainly in the legume family involves a very intimate interaction. Within the symbiotic organ (the nodule) the bacteria are fully internalized by the host cell to become an intracellular organelle surrounded by a host-derived membrane. This arrangement is probably necessary for the efficient provision of energy and the sequestration of free oxygen molecules, two conditions required for sustained nitrogen fixation. Recent advances made in model legume species, such as Medicago truncatula, are beginning to uncover the genetic components allowing rhizobia to access the host cytoplasm and establish chronic intracellular infections without overt detrimental effects...
May 17, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29778697/structural-basis-for-selective-inhibition-of-antibacterial-target-mray-a-membrane-bound-enzyme-involved-in-peptidoglycan-synthesis
#18
REVIEW
Jenny Hering, Elin Dunevall, Margareta Ek, Gisela Brändén
The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase)...
May 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29778605/proteomic-and-biochemical-comparison-of-the-cellular-interaction-partners-of-human-vps33a-and-vps33b
#19
Morag R Hunter, Geoffrey G Hesketh, Tomasz H Benedyk, Anne-Claude Gingras, Stephen C Graham
Multi-subunit tethering complexes control membrane fusion events in eukaryotic cells. CORVET and HOPS are two such complexes, both containing the Sec1/Munc18 protein subunit VPS33A. Metazoans additionally possess VPS33B, which has considerable sequence similarity to VPS33A but does not integrate into CORVET or HOPS complexes and instead stably interacts with VIPAR. It has been recently suggested that VPS33B and VIPAR comprise two subunits of a novel multi-subunit tethering complex (named "CHEVI"), perhaps analogous in configuration to CORVET and HOPS...
May 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29777694/gapdh-targeted-therapy-a-new-approach-for-secondary-damage-after-traumatic-brain-injury-on-rats
#20
Vladimir F Lazarev, Elizaveta A Dutysheva, Elena Y Komarova, Elena R Mikhaylova, Irina V Guzhova, Boris A Margulis
Massive neuronal death caused by a neurodegenerative pathology or damage due to ischaemia or traumatic brain injury leads to the appearance of cytosolic proteins in the extracellular space. We found that one of the most abundant cellular polypeptides, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), appearing in the medium of dying cells or body fluids is able to form aggregates that are cytotoxic to adjacent cells. Since we previously showed that the hydrocortisone derivative RX624 can inhibit the ability of GAPDH to transport the enzyme complex with polyglutamine and reduce the cytotoxicity of the complex, we explored the effects of GAPDH on SH-SY5Y neuroblastoma cells...
May 16, 2018: Biochemical and Biophysical Research Communications
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