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https://www.readbyqxmd.com/read/29150658/differential-regulation-of-synaptic-ap-2-clathrin-vesicle-uncoating-in-synaptic-plasticity
#1
Ermes Candiello, Ratnakar Mishra, Bernhard Schmidt, Olaf Jahn, Peter Schu
AP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B -/- mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150442/functional-analyses-of-a-human-vascular-tumor-fos-variant-identify-a-novel-degradation-mechanism-and-a-link-to-tumorigenesis
#2
David G P van Ijzendoorn, Zary Forghany, Frauke Liebelt, Alfred C Vertegaal, Aart G Jochemsen, Judith V M G Bovée, Karoly Szuhai, David A Baker
Epithelioid hemangioma is a locally aggressive vascular neoplasm, found in bones and soft tissue, whose cause is currently unknown, but may involve oncogene activation. FOS was one of the earliest viral oncogenes to be characterized and normal cellular FOS forms part of the activator protein 1 (AP-1) transcription factor complex which plays a pivotal role in cell growth, differentiation and survival as well as the DNA damage response. Despite this, to date, a causal link between aberrant FOS function and naturally occurring tumors has not been established...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29147073/metformin-suppressed-cxcl8-expression-and-cell-migration-in-hek293-tlr4-cell-line
#3
Zhihui Xiao, Wenjun Wu, Vladimir Poltoratsky
Chronic inflammation is associated with cancer. CXCL8 promotes tumor microenvironment construction through recruiting leukocytes and endothelial progenitor cells that are involved in angiogenesis. It also enhances tumor cell proliferation and migration. Metformin, type II diabetes medication, demonstrates anticancer properties via suppressing inflammation, tumor cell proliferation, angiogenesis, and metastasis. This study intended to address the role of metformin in regulation of CXCL8 expression and cell proliferation and migration...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29145973/tak-ing-aim-at-chemoresistance-the-emerging-role-of-map3k7-as-a-target-for-cancer-therapy
#4
Raffaela Santoro, Carmine Carbone, Geny Piro, Paul J Chiao, Davide Melisi
Cellular drug resistance remains the main obstacle to the clinical efficacy of cancer chemotherapy. Alterations in key pathways regulating cell cycle checkpoints, apoptosis and Epithelial to Mesenchymal Transition (EMT), such as the Mitogen-activated protein kinase (MAPK) pathway, appear to be closely associated to cancer chemoresistance. Transforming growth factor-β (TGF-β)- activated kinase 1 (TAK1, also known as MAP3K7) is a serine/threonine kinase in the mitogen-activated protein kinase (MAP3K) family...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145717/ctrp9-regulates-growth-differentiation-and-apoptosis-in-human-keratinocytes-through-tgf%C3%AE-1-p38-dependent-pathway
#5
Tae Woo Jung, Hyung Sub Park, Geum Hee Choi, Daehwan Kim, Taeseung Lee
Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 (TGFβ1) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dosedependent manner...
November 16, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29145394/unc-16-jip3-regulates-early-events-in-synaptic-vesicle-protein-trafficking-via-lrk-1-lrrk2-and-ap-complexes
#6
Bikash Choudhary, Madhushree Kamak, Neena Ratnakaran, Jitendra Kumar, Anjali Awasthi, Chun Li, Ken Nguyen, Kunihiro Matsumoto, Naoki Hisamoto, Sandhya P Koushika
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex...
November 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29144206/c-jun-expression-in-lichen-planus-psoriasis-and-cutaneous-squamous-cell-carcinoma-an-immunohistochemical-study
#7
Asmaa Gaber Abdou, Alaa Hassan Marae, Mohammed Shoeib, Ghada Dawood, Enas Abouelfath
The AP-1 transcription factor complex is a key player in regulating inflammatory processes, cell proliferation, differentiation and cell transformation. The aim of the present study is to investigate C-Jun (one of AP-1complex) expression and its proliferative role in skin samples of lichen planus, psoriasis as common inflammatory skin diseases and squamous cell carcinoma using immunohistochemical method. The present study was carried out on skin biopsies of 15 psoriatic patients, 15 lichen planus patients, 15 SCC and 15 normal skin biopsies...
November 16, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29139546/up-regulation-of-pyk2-pkc%C3%AE-dependent-ho-1-by-co-releasing-molecule-corm-2-attenuates-tnf-%C3%AE-induced-lung-inflammation
#8
Chih-Chung Lin, Yu-Ching Chiang, Rou-Ling Cho, Wei-Ning Lin, Chien-Chung Yang, Li-Der Hsiao, Chuen-Mao Yang
BACKGROUND AND PURPOSE: Heme oxygenase-1 (HO-1) could provide cytoprotection against various inflammatory diseases. However, the mechanisms underlying carbon monoxide-releasing molecule-2 (CORM-2)-induced HO-1 expression protecting against TNF-α-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unknown. EXPERIMENTAL APPROACH: CORM-2-induced HO-1 protein and mRNA expression, and signaling pathways were determined by Western blot and real-time PCR, coupled using respective pharmacological inhibitors or transfection with siRNAs...
November 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29138815/curcumin-reverses-tobacco-smoke%C3%A2-induced-epithelial%C3%A2-mesenchymal-transition-by-suppressing-the-mapk-pathway-in-the-lungs-of-mice
#9
Zhaofeng Liang, Rui Wu, Wei Xie, Mingming Zhu, Chunfeng Xie, Xiaoting Li, Jianyun Zhu, Weiwei Zhu, Jieshu Wu, Shanshan Geng, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for lung cancer. Epithelial‑mesenchymal transition (EMT) is decisive in cancer invasion and metastasis, and therefore promotes cancer progression. Mitogen‑activated protein kinase (MAPK) pathways are implicated in various aspects of cancer development and progression, including the EMT process. The chemopreventive effect of curcumin on carcinogenesis has been reported in vivo and in vitro. The present study investigated tobacco smoke‑induced alterations in the MAPK/activator protein‑1 (AP‑1) pathways, and pulmonary EMT changes in the lungs of mice, and further observed the chemopreventive effect of curcumin...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29131211/pharmaco-genomic-investigations-of-organo-iridium-anticancer-complexes-reveal-novel-mechanism-of-action
#10
Jessica M Hearn, George M Hughes, Isolda Romero-Canelón, Alison F Munro, Belén Rubio-Ruiz, Zhe Liu, Neil O Carragher, Peter J Sadler
Resistance to platinum drugs (used in >50% of cancer chemotherapies) is a clinical problem. Other precious metal complexes with distinct mechanisms of action might overcome this. Half-sandwich organometallic complexes containing arene or cyclopentadienyl (Cp) ligands show promise. We screened two iridium(iii) complexes [Ir(Cp(Xbiph))(ppy)Cl] (ZL49, 1, ppy = phenylpyridine) and [Ir(Cp(Xph))(azpyNMe2)Cl]PF6 (ZL109, 2, azpyNMe2 = N,N-dimethylphenylazopyridine) in 916 cancer cell lines from 28 tissue types. On average, complex 2 was 78× more potent than 1, 36× more active than cisplatin (CDDP), and strongly active (nanomolar) in patient-derived ovarian cancer cell lines...
November 13, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29130097/c-fos-mediates-%C3%AE-1-2-fucosyltransferase-1-and-lewis%C3%A2-y-expression-in-response-to-tgf-%C3%AE-1-in-ovarian-cancer
#11
Yingying Hao, Liancheng Zhu, Limei Yan, Juanjuan Liu, Dawo Liu, Na Gao, Mingzi Tan, Song Gao, Bei Lin
FUT1 is a key rate-limiting enzyme in the synthesis of Lewis y, a membrane-associated carbohydrate antigen. The aberrant upregulation of FUT1 and Lewis y antigen is related to proliferation, invasion and prognosis in malignant epithelial tumors. A c-Fos/activator protein-1 (AP-1) binding site was found in the FUT1 promoter. However, the mechanisms of transcriptional regulation of FUT1 remain poorly understood. TGF-β1 is positively correlated to Lewis y. In the present study, we investigated the molecular mechanism of FUT1 gene expression in response to TGF-β1...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29128803/the-effect-of-dehydroglyasperin-c-on-uvb-mediated-mmps-expression-in-human-hacat-cells
#12
Song Hua Xuan, Young Min Park, Ji Hoon Ha, Yoon Ju Jeong, Soo Nam Park
BACKGROUND: The ultraviolet B (UVB) from solar radiation increases the generation of reactive oxygen species (ROS), which mediate the production of matrix metalloproteinases (MMPs), and acts mainly on the epidermis layer of the skin. This study was aimed at assessing the anti-photoaging effects of dehydroglyasperin C isolated from Glycyrrhiza uralensis Fisch on MMPs levels in HaCaT human keratinocytes and to elucidate the underlying mechanism. METHODS: The cell viability was measured by MTT assay...
May 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29123471/vglut2-trafficking-is-differentially-regulated-by-adaptor-proteins-ap-1-and-ap-3
#13
Haiyan Li, Magda S Santos, Chihyung K Park, Yuriy Dobry, Susan M Voglmaier
Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29119451/pristimerin-inhibits-lps-triggered-neurotoxicity-in-bv-2-microglia-cells-through-modulating-irak1-traf6-tak1-mediated-nf-%C3%AE%C2%BAb-and-ap-1-signaling-pathways-in-vitro
#14
Bin Hui, Liping Zhang, Qinhua Zhou, Ling Hui
Microglia plays a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations and secreting inflammatory molecules. However, hyperactivated microglial is neurotoxic and plays critical roles in the pathogenesis of neurodegenerative diseases. Pristimerin, a naturally occurring triterpenoid, possesses antitumor, antioxidant, and anti-inflammatory activities. However, the effect and the molecular mechanism of pristimerin against lipopolysaccharide (LPS)-induced neurotoxicity in microglia remain to be revealed...
November 8, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29115531/liver-dual-arterial-blood-supply-maintains-liver-regeneration-analysis-of-signaling-pathways-in-rats
#15
Jian-Liang Qiao, Juan Sun, Jun Li, Jun-Jing Zhang, Xing-Kai Meng
Liver dual arterial blood supply (LDABS) could increase blood supply to the liver and maintain normal liver regeneration in patients with compromised portal vein. The current study attempted to examine the underlying molecular mechanisms. Male Sprague‑Dawley rats randomly received partial hepatectomy (PH) alone or PH followed by LDABS. Liver regeneration was assessed by histological examination, liver function and liver regeneration rate (LRR). Whole‑genome oligo microarray analysis was used to compare gene expression profile between rats receiving PH and rats receiving PH plus LDABS...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114611/2d-kv-orthogonal-imaging-with-fiducial-markers-is-more-precise-for-daily-image-guided-alignments-than-soft-tissue-cone-beam-computed-tomography-for-prostate-radiation-therapy
#16
Peter H Goff, Louis B Harrison, Eli Furhang, Evan Ng, Stephen Bhatia, Frieda Trichter, Ronald D Ennis
Purpose: The hypothesis is that 2-dimensional kV orthogonal imaging with fiducial markers (kV-FM) and soft-tissue cone beam computed tomography (ST-CBCT) are equally reproducible for daily positional alignments for image guided (IG) intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and materials: Ten patients undergoing definitive treatment for prostate cancer with IG-IMRT were imaged daily with kV-FM and ST-CBCT. For each acquired kV and CBCT image, offline alignments to the digitally reconstructed radiograph or planning CT, respectively, were made twice by the same physician to assess intraobserver test-retest reproducibility...
July 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29113952/do-all-roads-lead-to-the-rome-the-glycation-perspective
#17
REVIEW
Saheem Ahmad, Firoz Akhter, Uzma Shahab, Zeeshan Rafi, Mohd Sajid Khan, Rabia Nabi, Mohd Salman Khan, Khurshid Ahmad, Jalaluddin Mohammad Ashraf, Moinuddin
Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), β-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules...
November 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29112457/fosl1-promotes-kras-induced-lung-cancer-through-amphiregulin-and-cell-survival-gene-regulation
#18
Indira M Elangovan, Michelle Vaz, Chandramohan R Tamatam, Haranatha R Potteti, Narsa M Reddy, Sekhar P Reddy
RATIONALE: FOSL1/AP-1 transcription factor regulates gene expression controlling various pathophysiological processes. It is a major effector of RAS-ERK1/2 signaling and activated in human lung epithelia by tumorigenic stimuli. Recent evidence shows an inverse correlation between FOSL1 expression and the survival of lung cancer patients with adenocarcinomas; however its role in lung tumorigenesis remains elusive. OBJECTIVES: To determine the role of FOSL1 in Kras-induced lung adenocarcinoma in vivo, and its downstream effector mechanisms...
November 7, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29109235/glial-draper-rescues-a%C3%AE-toxicity-in-a-drosophila-model-of-alzheimer-s-disease
#19
Arpita Ray, Sean D Speese, Mary A Logan
Pathological hallmarks of Alzheimer's disease (AD) include amyloid-beta (Aβ) plaques, neurofibrillary tangles, and reactive gliosis. Glial cells offer protection against AD by engulfing extracellular Aβ peptides, but the repertoire of molecules required for glial recognition and destruction of Aβ are still unclear. Here, we show that the highly conserved glial engulfment receptor Draper/MEGF10 provides neuroprotection in an AD model of Drosophila (both sexes). Neuronal expression of human Aβ42(arc) in adult flies results in robust Aβ accumulation, neurodegeneration, locomotor dysfunction, and reduced lifespan...
November 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29108257/regulation-of-neuroinflammation-by-matrix-metalloproteinase-8-inhibitor-derivatives-in-activated-microglia-and-astrocytes
#20
Eun-Jung Lee, Min-Ji Choi, Gyeongjin Lee, Bhakta Prasad Gaire, Ji Woong Choi, Hee-Sun Kim
Matrix metalloproteinases (MMPs) play a pivotal role in neuroinflammation that is associated with neurodegenerative diseases. Our group recently reported that MMP-8 mediates inflammatory reactions by modulating the processing of TNF-α. To improve the efficacy of the currently available MMP-8 inhibitor (M8I), we have synthesized structurally modified M8I derivatives (comp 2, 3, 4, 5) and compared their efficacy with original compound (comp 1). Among M8I derivatives, comp 2, 3, and 5 inhibited the production of NO, ROS, and IL-6 more efficiently than the original compound in lipopolysaccharide (LPS)-stimulated microglia...
October 3, 2017: Oncotarget
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