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https://www.readbyqxmd.com/read/28634786/inhibition-of-nf-%C3%AE%C2%BAb-activity-by-aminoguanidine-alleviates-neuroinflammation-induced-by-hyperglycemia
#1
Yuanjian Song, Fang Zhang, Changjiang Ying, Kiran Ashok Kumar, Xiaoyan Zhou
Neuroinflammation is a key feature of cerebral complication which is associated with diabetes mellitus (DM). Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of neuroinflammation. However, how iNOS facilitates the development of inflammation in brain is still unidentified. The aim of the present study was to investigate the association of iNOS and neuroinflammation in diabetic mice, and elucidate the potential mechanisms underlying aminoguanidine (AG), the selective inhibitor of iNOS, protected neurons against inflammation in diabetic mice...
June 20, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28634583/circular-rnas-biogenesis-function-and-role-in-human-diseases
#2
REVIEW
John Greene, Anne-Marie Baird, Lauren Brady, Marvin Lim, Steven G Gray, Raymond McDermott, Stephen P Finn
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28634572/a-helicobacter-pylori-homolog-of-eukaryotic-flotillin-is-involved-in-cholesterol-accumulation-epithelial-cell-responses-and-host-colonization
#3
Melanie L Hutton, Kimberley D'Costa, Amanda E Rossiter, Lin Wang, Lorinda Turner, David L Steer, Seth L Masters, Ben A Croker, Maria Kaparakis-Liaskos, Richard L Ferrero
The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28634242/type-ii-secretion-substrates-of-legionella-pneumophila-translocate-out-of-the-pathogen-occupied-vacuole-via-a-semipermeable-membrane
#4
Hilary K Truchan, Harry D Christman, Richard C White, Nakisha S Rutledge, Nicholas P Cianciotto
Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28634224/igh-myc-translocation-associates-with-brca2-deficiency-and-synthetic-lethality-to-parp1-inhibitors
#5
Silvia Maifrede, Kayla Martin, Paulina Podszywalow-Bartnicka, Katherine Sullivan, Samantha K Langer, Reza Nejadi, Yashodhara Dasgupta, Michael Hulse, Daniel Gritsyuk, Margaret Nieborowska-Skorska, Lena N Lupey-Green, Huaqing Zhao, Katarzyna Piwocka, Mariusz A Wasik, Italo Tempera, Tomasz Skorski
Burkitt lymphoma/leukemia (BL) cells carry t(8;14)(q24;q32) chromosomal translocation encoding IGH/MYC, which results in the constitutive expression of the MYC oncogene. Here, it is demonstrated that untreated and cytarabine (AraC)-treated IGH/MYC-positive BL cells accumulate a high number of potentially lethal DNA double-strand breaks (DSBs) and display low levels of the BRCA2 tumor suppressor protein, which is a key element of homologous recombination (HR)-mediated DSB repair. BRCA2 deficiency in IGH/MYC-positive cells was associated with diminished HR activity and hypersensitivity to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors (olaparib, talazoparib) used alone or in combination with cytarabine in vitro...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#6
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28633978/airborne-nitro-pahs-induce-nrf2-are-defense-system-against-oxidative-stress-and-promote-inflammatory-process-by-activating-pi3k-akt-pathway-in-a549-cells
#7
Yu Shang, Qian Zhou, Tiantian Wang, Yuting Jiang, Yufang Zhong, Guangren Qian, Tong Zhu, Xinghua Qiu, Jing An
Ambient particulate matter (PM) is a worldwide health issue of concern. However, limited information is available regarding the toxic contributions of the nitro-derivatives of polycyclic aromatic hydrocarbons (nitro-PAHs). This study intend to examine whether 1-nitropyrene (1-NP) and 3-nitrofluoranthene (3-NF) could activate the nuclear factor-erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) antioxidant defense system, and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway participates in regulating pro-inflammatory responses in A549 cells...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28632030/ultraviolet-b-radiation-stimulates-the-interaction-between-nuclear-factor-of-activated-t-cells-5-nfat5-and-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-in-human-lens-epithelial-cells
#8
Inyoung Chung, Young-Sool Hah, SunMi Ju, Ji-Hye Kim, Woong-Sun Yoo, Hee-Young Cho, Ji-Myong Yoo, Seong-Wook Seo, Wan-Sung Choi, Seong-Jae Kim
PURPOSE: Nuclear factor-kappa B (NF-κB) has been proposed as a therapeutic target for the treatment of cataracts. The authors investigated the relationship between nuclear factor of activated T cells 5 (NFAT5) and NF-κB in ultraviolet B (UVB)-irradiated human lens epithelial (HLE) cells. METHODS: Human lens epithelial B-3 (HLE-B3) cells were exposed to UVB light at a dose of 10 mJ/cm(2) and then incubated for 24 h. Cell viability was assessed by using the Cell Counting Kit-8 (CCK-8) assay...
February 26, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28631426/hsp90%C3%AE-regulates-atm-and-nbn-functions-in-sensing-and-repair-of-dna-double-strand-breaks
#9
Rosa Pennisi, Antonio Antoccia, Stefano Leone, Paolo Ascenzi, Alessandra di Masi
The molecular chaperone heat shock protein 90 (Hsp90α) regulates cells proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ATM and NBN, but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cells lines...
June 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28631302/l-hcy-induced-cathepsin-v-mediates-the-vascular-endothelial-inflammation-in-hyperhomocysteinemia
#10
Yi-Ping Leng, Ye-Shuo Ma, Xiao-Gang Li, Rui-Fang Chen, Ping-Yu Zeng, Xiao-Hui Li, Cheng-Feng Qiu, Ya-Pei Li, Zhen Zhang, Alex F Chen
BACKGROUND AND PURPOSE: Vascular inflammation, including the expression of inflammatory cytokines in endothelial cells, plays a critical role in hyperhomocysteinemia-associated vascular diseases. Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on the L-homocysteine (L-Hcy)-induced vascular inflammation. EXPERIMENTAL APPROACH: A high methionine diet-induced hyperhomocysteinemic mice model was used to assess the cathepsin V expression and vascular inflammation...
June 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28630296/subunit-specific-role-for-the-amino-terminal-domain-of-ampa-receptors-in-synaptic-targeting
#11
Javier Díaz-Alonso, Yujiao J Sun, Adam J Granger, Jonathan M Levy, Sabine M Blankenship, Roger A Nicoll
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630284/differential-interaction-of-dantrolene-glafenine-nalidixic-acid-and-prazosin-with-human-organic-anion-transporters-1-and-3-oat1-oat3
#12
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
In renal proximal tubule cells, the organic anion transporters 1 and 3 (OAT1 and OAT3) in the basolateral membrane and the multi drug resistance-associated protein 4 (MRP4) in the apical membrane share substrates and co-operate in renal drug secretion. We hypothetized that recently identified MRP4 inhibitors, dantrolene, glafenine, nalidixic acid, and prazosin, also interact with human OAT1 and/or OAT3 stably transfected in HEK293 cells. These four drugs were tested as possible inhibitors of p-[3H]aminohippurate (PAH) and [14C]glutarate uptake by OAT1, and of [3H]estrone-3-sulfate (ES) uptake by OAT3...
June 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28630256/the-small-gtpase-rac1-contributes-to-extinction-of-aversive-memories-of-drug-withdrawal-by-facilitating-gabaa-receptor-endocytosis-in-the-vmpfc
#13
Wei-Sheng Wang, Yun-Yue Ju, Qi-Xin Zhou, Jian-Xin Tang, Meng Li, Lei Zhang, Shuo Kang, Zhong-Guo Chen, Yu-Jun Wang, Hui Ji, Yu-Qiang Ding, Lin Xu, Jing-Gen Liu
Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABAA receptor (GABAAR) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28630091/b-1a-cells-protect-mice-from-sepsis-critical-role-of-creb
#14
Monowar Aziz, Nichol E Holodick, Thomas L Rothstein, Ping Wang
Bacterial sepsis is a serious life-threatening condition caused by an excessive immune response to infection. B-1 cells differ from conventional B-2 cells by their distinct phenotype and function. A subset of B-1 cells expressing CD5, known as B-1a cells, exhibits innate immune activity. Here we report that B-1a cells play a beneficial role in sepsis by mitigating exaggerated inflammation through a novel mechanism. Using a mouse model of bacterial sepsis, we found that the numbers of B-1a cells in various anatomical locations were significantly decreased...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28630074/the-enterohaemorrhagic-escherichia-coli-effector-espw-triggers-actin-remodeling-in-a-rac1-dependent-manner
#15
Pamela Sandu, Valerie F Crepin, Hauke Drechsler, Andrew D McAinsh, Gad Frankel, Cedric N Berger
Enterohaemorrhagic Escherichia coli (EHEC) is a diarrheagenic pathogen that colonizes the gut mucosa and induces attaching-and-effacing lesions. EHEC employs a type III secretion system (T3SS) to translocate 50 effector proteins that hijack and manipulate host cell signalling pathways, which allow bacterial colonization, subversion of immune responses and disease progression. The aim of this study was to characterize the T3SS effector EspW. We found espW in the sequenced O157:H7 and non-O157 EHEC strains as well as in Shigella boydii Furthermore, a truncated version of EspW, containing the first 206 residues is present in EPEC strains belonging to serotype O55:H7...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28629997/membrane-translocation-of-transient-receptor-potential-ankyrin-1-induced-by-inflammatory-cytokines-in-lung-cancer-cells
#16
Kenji Takahashi, Toshio Ohta
Transient receptor potential ankyrin 1 (TRPA1) is known as one of the nociceptors expressed in sensory neurons. It also plays a role in non-neural cells in inflammatory sites. However, the regulatory mechanisms for the reactivity of TRPA1 in these cells under inflammatory conditions are not clear. To clarify these mechanisms, we examined the effects of inflammatory cytokines (interleukin [IL]-1α, IL-1β and tumor necrosis factor α [TNFα]) on TRPA1 reactivity and expression in the endogenously TRPA1-expressing lung tumor cell line A549...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629334/protein-kinase-c-%C3%AE-pkc%C3%AE-modulates-cell-apoptosis-by-stimulating-nuclear-translocation-of-nf-kappa-b-p65-in-urothelial-cell-carcinoma-of-the-bladder
#17
Jin Zheng, Chuize Kong, Xiaoxi Yang, Xiaolu Cui, Xuyong Lin, Zhe Zhang
BACKGROUND: The protein kinase C (PKC) family comprises central regulators of multiple signal transduction processes and is involved in the progression of many cancers. Nuclear factor Kappa-B (NF-κB) is constitutively expressed in cancer tissues and stimulates the transcription of various tumor-related genes. The present study aims to investigate the clinical significance of PKCα and NF-κB p65 in bladder cancer tissues and the mechanism underlying PKCα induction of bladder cancer cell apoptotic resistance through stimulation of p65 nuclear translocation...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28628091/the-btg2-prmt1-module-limits-pre-b-cell-expansion-by-regulating-the-cdk4-cyclin-d3-complex
#18
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J Fiala, Susana Minguet, Bettina Warscheid, David M Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28627642/effect-of-retinoid-x-receptor-%C3%AE-nuclear-export-inhibition-on-apoptosis-of-neurons-in%C3%A2-vivo-and-in%C3%A2-vitro
#19
Yingchun Liu, Jiangguo Tang, Xiaoxiao Gao, Min Wang, Jie Shen, Xiaoqing You
Alzheimer's disease (AD), which is characte-rized by excessive apoptosis of neurons, is considered to be a global public health crisis. Retinoid-induced apoptosis is dependent on the orphan nuclear receptor Nur77, a transcription factor that is expressed predominantly in brain tissues. Nur77 nuclear export requires retinoid X receptor‑α (RXRα) as a carrier. However, the involvement of Nur77 in mediating β‑amyloid (Aβ)‑induced neuronal apoptosis has not yet been elucidated. The primary aim of the present study was to investigate the potential of Nur77 in Aβ‑induced neuron apoptosis, and to evaluate the effect of RXRα nuclear export inhibition on neuronal apoptosis...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627613/translocation-of-enterohemorrhagic-escherichia%C3%A2-coli-effector-tir-to-the-plasma-membrane-via-host-golgi-apparatus
#20
Chan Mao, Jiang Gu, Hai-Guang Wang, Yao Fang, Ping Yang, Bin Tang, Na Li, Ting-Ting Wang, Quan-Ming Zou, Qian Li
The translocated intimin receptor (Tir) is a canonical type III secretion system effector, secreted by the enterohemorrhagic Escherichia coli (E. coli). This receptor alters the regular cellular processing of host cells, to promote intracellular bacterial replication and evasion of the host immune system. Tir is translocated and integrated into the host cell plasma membrane, a process required for its pathogenic activity in these cells, however, the underlying mechanisms of how this occurs remain to be elucidated...
June 13, 2017: Molecular Medicine Reports
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