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María Victoria Repetto, Matthew J Winters, Alan Bush, Wolfgang Reiter, David Maria Hollenstein, Gustav Ammerer, Peter M Pryciak, Alejandro Colman-Lerner
We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages...
March 15, 2018: Molecular Cell
Amjad M Husaini, Aafreen Sakina, Souliha R Cambay
Fusarium oxysporum, a ubiquitous soil-borne pathogen causes devastating vascular wilt in more than 100 plant species and ranks fifth among top ten fungal plant pathogens. It has emerged as a human pathogen too, causing infections in immune-compromised patients. It is, therefore, important to gain insight into the molecular processes involved in the pathogenesis of this trans-kingdom pathogen. A complex network comprising of interconnected and over lapping signal pathways; mitogen-activated protein kinase (MAPK) signaling pathways, Ras proteins, G-protein signaling components and their downstream pathways, components of the velvet (LaeA/VeA/VelB) complex and cAMP pathways, is involved in perceiving the host...
March 16, 2018: Molecular Plant-microbe Interactions: MPMI
Md Moniruzzaman, Young-Won Chin, Jungsook Cho
Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells...
March 15, 2018: Cell Stress & Chaperones
Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
Tao Wang, Hui Zhao, Hua Gao, Changming Zhu, Yao Xu, Liping Bai, Junbo Liu, Feng Yan
The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are activated during pathogenesis of gastrointestinal stromal tumors (GISTs). Forkhead box protein O1 (FOXO1) is a transcription factor regulated by the MAPK and PI3K pathways and is associated with multiple metabolic reactions. The present study aims to investigate the association of FOXO1 with cell proliferation and apoptosis in the cell line, GIST-T1. Cell counting kit-8 assay revealed that cell growth was inhibited by the PI3K inhibitor, LY294002, and/or MAPK inhibitor, UO126...
April 2018: Experimental and Therapeutic Medicine
Yuh-Charn Lin, Chun-Yu Liu, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), expressed on the endothelial cell surface, functions as a novel coreceptor for VEGFR2 (vascular endothelial growth factor receptor 2) and enhances VEGF-induced signaling in adult angiogenesis. However, whether SCUBE2 plays a role in pathological angiogenesis and whether anti-SCUBE2 antibody is an effective strategy for blocking tumor angiogenesis remain unknown. The aim of this study was to investigate the pathological role and targeting therapy of SCUBE2 in tumor vasculature...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Nan Zhang, Lei Zhang, Linyin Feng, Lei Yao
ETHNOPHARMACOLOGICAL RELEVANCE: Cananga odorata essential oil, known as ylang-ylang essential oil (YYO), was commonly used in the aromatherapy for relaxation and mood adjusting use. In our previous study, YYO played anxiolytic effects on the mice in several behavioral tests that based on the instinctive responses to novel environments. AIM OF THE STUDY: To investigate the effects and mechanisms of YYO reversing the anxiety induced by 5-HT2C receptor agonist 1-(3-chlorophenyl) piperazine (m-CPP)...
March 12, 2018: Journal of Ethnopharmacology
G Vázquez-Gómez, L Rocha-Zavaleta, M Rodríguez-Sosa, P Petrosyan, J Rubio-Lightbourn
Benzo[a]pyrene (B[a]P), the most extensively studied carcinogen in cigarette smoke, has been regarded as a critical mediator of lung cancer. It is known that B[a]P-mediated Aryl hydrocarbon Receptor (AhR) activation stimulates the mitogen activated protein kinases (MAPK) signaling cascade in different cell models. MAPK pathway disturbances drive alterations in cellular processes, such as differentiation, proliferation, and apoptosis, and the disturbances may also modify the AhR pathway itself. However, MAPK involvement in B[a]P metabolic activation and toxicity in lung tissues is not well understood...
March 12, 2018: Toxicology Letters
Jinfeng Cui, Juan Wang, Shujuan Huang, Xiujuan Jiang, Yuehong Li, Wenxin Wu, Xianghong Zhang
Sterigmatocystin (ST), being a precursor of aflatoxin, is categorized as Group 2B carcinogen. Our previous studies found that both mismatch repair (MMR) pathways and p53 signaling pathway were involved in ST-induced G2 cell cycle arrest in human esophageal squamous epithelial cell line, HET-1A, in vitro. Studies showed that ERK, JNK and p38 signaling pathways played important roles in cell cycle arrest induced by several other carcinogens. However, the role of MAPK pathway and the links between the MMR and p53 signaling pathways in ST induced G2 phase arrest is still not clarified...
March 12, 2018: Food and Chemical Toxicology
Yaoming Peng, Jiabin Lin, Junyan Ma, Kaiqing Lin, Kaihong Xu, Jun Lin
S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion...
March 16, 2018: Gynecological Endocrinology
Yoshitoshi Kasuya, Hiroki Umezawa, Masahiko Hatano
Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves...
March 15, 2018: International Journal of Molecular Sciences
Takuya Wakamatsu, Suguru Yamamoto, Toru Ito, Yoko Sato, Koji Matsuo, Yoshimitsu Takahashi, Yoshikatsu Kaneko, Shin Goto, Junichiro James Kazama, Fumitake Gejyo, Ichiei Narita
In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay...
March 15, 2018: Toxins
Yawen Li, Fangming Xiu, Zezhong Mou, Zhiwei Xue, Huanhui Du, Chunxue Zhou, Yan Li, Yongyu Shi, Shenyi He, Huaiyu Zhou
AIM: Exosomes are nanoscale membranous vesicles secreted by most cell types able to transfer bioactive molecules among cells, which play crucial roles in intercellular communication. We characterized the exosomes derived from Toxoplasma gondii (T. gondii) and detected the immune response in macrophages. METHODS: We used transmission electron microscopy, nanotracking analysis and western blotting to identify T. gondii exosomes. Functional experiments were performed in RAW264...
March 15, 2018: Nanomedicine
John R Apps, Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Julie E Cooper, Saba Manshaei, Nital Jani, Annett Hölsken, Benedetta Pettorini, Robert J Beynon, Deborah M Simpson, Helen C Fraser, Ying Hong, Shirleen Hallang, Thomas J Stone, Alex Virasami, Andrew M Donson, David Jones, Kristian Aquilina, Helen Spoudeas, Abhijit R Joshi, Richard Grundy, Lisa C D Storer, Márta Korbonits, David A Hilton, Kyoko Tossell, Selvam Thavaraj, Mark A Ungless, Jesus Gil, Rolf Buslei, Todd Hankinson, Darren Hargrave, Colin Goding, Cynthia L Andoniadou, Paul Brogan, Thomas S Jacques, Hywel J Williams, Juan Pedro Martinez-Barbera
Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset...
March 14, 2018: Acta Neuropathologica
Marjan Nokhbehsaim, Svenja Memmert, Anna Damanaki, Shanika Nanayakkara, Xiaoyan Zhou, Andreas Jäger, James Deschner
OBJECTIVES: Periodontopathogens induce immunoinflammatory responses characterized by the release of inflammatory mediators, e.g., interleukin (IL)-1β, IL-6, and IL-8. Ghrelin (GHRL) is an appetite hormone which mediates its effect via the functional receptor GHS-R1a. This study was to examine the effect of an inflammatory insult on GHS-R1a in human periodontal cells. MATERIALS AND METHODS: Periodontal ligament (PDL) cells and gingival fibroblasts (HGFs) were exposed to IL-1β in the presence and absence of GHRL...
March 14, 2018: Clinical Oral Investigations
Giulio Calcagni, Giuseppe Limongelli, Angelo D'Ambrosio, Francesco Gesualdo, Maria Cristina Digilio, Anwar Baban, Sonia B Albanese, Paolo Versacci, Enrica De Luca, Giovanni B Ferrero, Giuseppina Baldassarre, Gabriella Agnoletti, Elena Banaudi, Jan Marek, Juan P Kaski, Giulia Tuo, Maria Giovanna Russo, Giuseppe Pacileo, Ornella Milanesi, Daniela Messina, Maurizio Marasini, Francesca Cairello, Roberto Formigari, Maurizio Brighenti, Bruno Dallapiccola, Marco Tartaglia, Bruno Marino
A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies) was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET), collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed...
February 2018: Data in Brief
Luping Wang, Hushan Wang, Zongsheng Duan, Jian Zhang, Wenwen Zhang
This study investigated the protective effect ofgastrodin on cell apoptosis in rats hippocampus tissues induced by desflurane to explore its mechanism. A total of 36 rats were randomly divided into three groups: Blank control group (C group, n=12), desflurane anesthesia group (DF group, n=12) and gastrodin treatment group (GT group, n=12). Rats in DF group were treated with anesthesia using desflurane. Rats in GT group were treated with gavage using gastrodin and the same treatment as DF group. After the experiment, novel object recognition test and water maze test were performed...
March 2018: Experimental and Therapeutic Medicine
Joanna Stanicka, Leonie Rieger, Sandra O'Shea, Orla Cox, Michael Coleman, Ciara O'Flanagan, Barbara Addario, Nuala McCabe, Richard Kennedy, Rosemary O'Connor
IGF-1 receptor (IGF-1R) and integrin cooperative signaling promotes cancer cell survival, proliferation, and motility, but whether this influences cancer progression and therapy responses is largely unknown. Here we investigated the non-receptor tyrosine adhesion kinase FES-related (FER), following its identification as a potential mediator of sensitivity to IGF-1R kinase inhibition in a functional siRNA screen. We found that FER and the IGF-1R co-locate in cells and can be co-immunoprecipitated. Ectopic FER expression strongly enhanced IGF-1R expression and phosphorylation on tyrosines 950 and 1131...
March 15, 2018: Oncogene
Matthew Dankner, April A N Rose, Shivshankari Rajkumar, Peter M Siegel, Ian R Watson
The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer. Approximately 50% of melanoma patients possess a druggable hotspot V600E/K mutation in the BRAF protein kinase. FDA-approved combination therapies of BRAF and MEK inhibitors are available that provide survival benefits to patients with a BRAF V600 mutation. Non-V600 BRAF mutants are found in many cancers, and are more prevalent than V600 mutations in certain tumor types. For example, between 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode for non-V600 mutants...
March 15, 2018: Oncogene
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
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