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Birgitte Georg, Birgitte Falktoft, Jan Fahrenkrug
The neuropeptide PACAP is expressed throughout the central and peripheral nervous system where it modulates diverse physiological functions including neuropeptide gene expression. We here report that in human neuroblastoma NB-1 cells PACAP transiently induces its own expression. Maximal PACAP mRNA expression was found after stimulation with PACAP for 3h. PACAP auto-regulation was found to be mediated by activation of PACAP specific PAC1Rs as PACAP had >100-fold higher efficacy than VIP, and the PAC1R selective agonist Maxadilan potently induced PACAP gene expression...
September 30, 2016: Neuropeptides
Chun Pang, Liang Shi, Yuchen Sheng, Zhiyong Zheng, Hai Wei, Zhengtao Wang, Lili Ji
Caffeic acid (CA) is a natural compound abundant in fruits, coffee and plants. This study aims to investigate the involved mechanism of the therapeutic detoxification of CA against acetaminophen (APAP)-induced hepatotoxicity. CA (10, 30 mg/kg) was orally given to mice at 1 h after mice were pre-administrated with APAP (300 mg/kg). The therapeutic detoxification of CA against APAP-induced hepatotoxicity was observed by detecting serum aminotransferases, liver malondialdehyde (MDA) amount and liver histological evaluation in vivo...
October 6, 2016: Chemico-biological Interactions
Stephanie L Grella, Mélanie F Guigueno, David J White, David F Sherry, Diano F Marrone
In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts...
2016: PloS One
Eun Ji Choi, Nam Jin Yoo, Min Sung Kim, Chang Hyeok An, Sug Hyung Lee
OBJECTIVE: The transcription factor-encoding EGR1 and the kinase-encoding BRSK1 are considered putative tumor suppressor genes (TSGs). However, EGR1 and BRSK1 mutations that could inactivate their functions are not reported in colorectal (CRC) and gastric (GC) cancers. METHODS: There are mononucleotide repeats in EGR1 and BRSK1, which could be mutated in cancers with defects in mismatch repair, resulting in microsatellite instability (MSI). We analyzed 124 CRCs and 79 GCs for mutations and their intratumoral heterogeneities (ITHs)...
September 28, 2016: Oncology
Lihua Song, Aiying Du, Ying Xiong, Jing Jiang, Yao Zhang, Zhaofeng Tian, Hongli Yan
γ-Aminobutyric acid (GABA) is a natural non-protein amino acid, which broadly exists in many plant parts and is widely used as an ingredient in the food industry. In mammals, it is widely distributed in central nervous system and non-neural tissues. In addition to a primary inhibitory neurotransmitter in the central nervous system, endogenous GABA content has been found to be elevated in neoplastic tissues in colon cancer. However, the effect of extraneous GABA on colon cancer has rarely been reported. In this study, we found the inhibitory effects of GABA on the proliferation of colon cancer cells (CCCs)...
September 19, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Mei Lin, Junxing Huang, Xingmao Jiang, Jia Zhang, Hong Yu, Jun Ye, Dongsheng Zhang
Combination targeted therapy is a promising cancer therapeutic strategy. Here, using PEI-Mn0.5Zn0.5Fe2O4 nanoparticles (PEI-MZF-NPs) as magnetic media for MFH (magnetic fluid hyperthermia) and gene transfer vector for gene-therapy, a combined therapy, pHRE-Egr1-HSV-TK/(131)I-antiAFPMcAb-GCV/MFH, for hepatoma is developed. AntiAFPMcAb (Monoclonal antibody AFP) is exploited for targeting. The plasmids pHRE-Egr1-HSV-TK are achieved by incorporation of pEgr1-HSV-TK and pHRE-Egr1-EGFP. Restriction enzyme digestion and PCR confirm the recombinant plasmids pHRE-Egr1-HSV-TK are successfully constructed...
2016: Scientific Reports
Jin Nishino, Miwa Yamazaki, Masanobu Kawai, Kanako Tachikawa, Keiko Yamamoto, Kazuaki Miyagawa, Mikihiko Kogo, Keiichi Ozono, Toshimi Michigami
Dentin matrix protein 1 (DMP1) is an extracellular matrix protein involved in phosphate metabolism and biomineralization, and its expression markedly increases during the maturation of osteoblasts into osteocytes. We previously reported that an increased level of inorganic phosphate (Pi) in media up-regulated the expression of Dmp1 in primary osteocytes isolated from mouse bones. In the present study, we found that elevated extracellular Pi strongly induced the expression of Dmp1 in osteoblasts and explored its underlying mechanism of action...
September 17, 2016: Journal of Cellular Biochemistry
Christian H Gabriel, Fridolin Gross, Martin Karl, Heike Stephanowitz, Anna Floriane Hennig, Melanie Weber, Stefanie Gryzik, Ivo Bachmann, Katharina Hecklau, Jürgen Wienands, Johannes Schuchhardt, Hanspeter Herzel, Andreas Radbruch, Eberhard Krause, Ria Baumgrass
Transcription factors of the nuclear factor of activated T cell (NFAT)-family are essential for antigen-specific T cell activation and differentiation. Their cooperative DNA binding with other transcription factors, such as AP1-proteins (FOS, JUN, JUNB), FOXP3, IRFs and EGR1, dictate the gene regulatory action of NFATs. To identify as yet unknown interaction partners of NFAT, we purified biotin tagged NFATc1/αA, NFATc1/βC and NFATc2/C protein-complexes and analyzed their components by SILAC-based mass spectrometry...
September 16, 2016: Journal of Biological Chemistry
Daniel Veraguas, Paula F Gallegos, Alejandra E Velasquez, Fidel O Castro, Lleretny Rodriguez-Alvarez
In the domestic cat, the efficiency of in vitro embryo production systems is negatively affected during the nonbreeding season. The objective of this research was to evaluate the effect of FSH stimulation in anestrous cats, on quality of cumulus-oocyte complexes (COCs) and in vitro developmental competence after parthenogenetic activation. To accomplish this purpose, anestrous cats were grouped into: (1) FSH treated (serial doses of 5 mg of porcine FSH each, every 24 hours, for 4 days) and (2) untreated control...
August 13, 2016: Theriogenology
M Mikula, M Skrzypczak, K Goryca, K Paczkowska, J K Ledwon, M Statkiewicz, M Kulecka, M Grzelak, M Dabrowska, U Kuklinska, J Karczmarski, I Rumienczyk, K Jastrzebski, M Miaczynska, K Ginalski, K Bomsztyk, J Ostrowski
Genome-wide mechanisms that coordinate expression of subsets of functionally related genes are largely unknown. Recent studies show that receptor tyrosine kinases and components of signal transduction cascades including the extracellular signal-regulated protein kinase (ERK), once thought to act predominantly in the vicinity of plasma membrane and in the cytoplasm, can be recruited to chromatin encompassing transcribed genes. Genome-wide distribution of these transducers and their relationship to transcribing RNA polymerase II (Pol2) could provide new insights about co-regulation of functionally related gene subsets...
September 1, 2016: Nucleic Acids Research
Linda Yu, Kyle Ham, Xiaohua Gao, Lysandra Castro, Yitang Yan, Grace E Kissling, Charles J Tucker, Norris Flagler, Ray Dong, Trevor K Archer, Darlene Dixon
BACKGROUND: The phytoestrogen, genistein at low doses nongenomically activates mitogen-activated protein kinase p44/42 (MAPKp44/42) via estrogen receptor alpha (ERα) leading to proliferation of human uterine leiomyoma cells. In this study, we evaluated if MAPKp44/42 could activate downstream effectors such as mitogen- and stress-activated protein kinase 1 (MSK1), which could then epigenetically modify histone H3 by phosphorylation following a low dose (1 μg/ml) of genistein. RESULTS: Using hormone-responsive immortalized human uterine leiomyoma (ht-UtLM) cells, we found that genistein activated MAPKp44/42 and MSK1, and also increased phosphorylation of histone H3 at serine10 (H3S10ph) in ht-UtLM cells...
2016: Cell Communication and Signaling: CCS
Bin Wang, Jia Guo, Lu Feng, Chun-Wai Suen, Wei-Ming Fu, Jin-Fang Zhang, Gang Li
Collagen formation is used as a crucial indicator of tenogenic differentiation of human tendon derived stem cell (hTDSC). Early growth response-1(egr1), a transcriptional factor, has been demonstrated to regulate tendon differentiation and promote tendon repair. Considering that the therapeutic options for tendon injuries remain limited, investigating the regulation of egr1 could facilitate the understanding of tendon development at molecular level so as to find a promising therapeutic target. MicroRNAs (miRNA) have been considered as epigenetic regulators to mediate multiple biological activities including stem cell differentiation...
October 1, 2016: Experimental Cell Research
Laura M Belluscio, Carolina D Alberca, Nicolás Pregi, Eduardo T Cánepa
Perinatal development represents a critical period in the life of an individual. A common cause of poor development is that which comes from undernutrition or malnutrition. In particular, protein deprivation during development has been shown to have deep deleterious effects on brain's growth and plasticity. Early life stress has also been linked with an increased risk to develop different psychopathologies later in life. We have previously shown that perinatal protein malnutrition in mice leads to the appearance of anxiety-related behaviors in the adulthood...
August 24, 2016: Genes, Brain, and Behavior
Van T T Huynh, Yun-Sook Lim, Si C Tran, Tu M Pham, Lam N Nguyen, Soon B Hwang
The propagation of hepatitis C virus (HCV) is highly dependent on host cellular factors. In order to identify the cellular factors involved in HCV propagation, we have previously performed protein microarray assays using the HCV nonstructural 5A (NS5A) protein as a probe. Out of ~9,000 host proteins immobilized in a microarray, approximately 90 cellular proteins were identified as HCV NS5A interacting partners. Of these candidates, we selected Abelson interactor 1 (Abi1) for further characterization. Binding of HCV NS5A to Abi1 was verified by both in vitro pulldown and coimmunoprecipitation assays...
August 22, 2016: Journal of Biological Chemistry
Oona Delpuech, Claire Rooney, Lorraine Mooney, Dawn Baker, Robert Shaw, Michael Dymond, Dennis Wang, Pei Zhang, Sarah Cross, Margaret H Veldman-Jones, Joanne Wilson, Barry R Davies, Jonathan R Dry, Elaine Kilgour, Paul D Smith
The challenge of developing effective pharmacodynamic biomarkers for pre-clinical and clinical testing of FGFR signalling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signalling inhibition by AZD4547, a potent inhibitor of FGF receptor 1, 2 and 3, a gene expression profiling study was performed in FGFR2 amplified, drug sensitive tumour cell lines...
August 22, 2016: Molecular Cancer Therapeutics
Lora J Rogers, Alexei G Basnakian, Mohammed S Orloff, Baitang Ning, Aiwei Yao-Borengasser, Vinay Raj, Susan Kadlubar
BACKGROUND: 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a heterocyclic aromatic amine (HCA) formed in meat that is cooked at high temperatures and then ingested, can potentially be retained in human adipose tissues. METHODS: To determine if PhIP is bioactive in the adipocyte, we exposed a human adipocyte cell line,HepG2 and Caco-2 cells to low dose PhIP. Uptake and retention of PhIP was determined and cytotoxicity was assessed by the TUNEL assay. Relative expression of PhIP-activating genes (CYP1A1, CYP1A2, SULT1A1 and UGT1A1) was determined by RT-PCR and global expression changes were also examined...
2016: Nutrition & Metabolism
Pra da Rosa, Amp Dau, M P De Cesaro, J T Dos Santos, B G Gasperin, R Duggavathi, V Bordignon, Pbd Gonçalves
The LH surge induces functional and morphological changes in granulosa cells. Mechanistic target of rapamycin (mTOR) is an integrator of signalling pathways in multiple cell types. We hypothesized that mTOR kinase activity integrates and modulates molecular pathways induced by LH in granulosa cells during the preovulatory period. Cows were ovariectomized and granulosa cells collected at 0, 3, 6, 12 and 24 hr after GnRH injection. While RHEB mRNA levels increased at 3 and 6 hr, returning to basal levels by 12 hr after GnRH treatment, RHOA mRNA levels increased at 6 hr and remained high thereafter...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
Elsie Samakai, Robert Hooper, Kayla A Martin, Maya Shmurak, Yi Zhang, Dietmar J Kappes, Italo Tempera, Jonathan Soboloff
Antigen presentation to the T cell receptor leads to sustained cytosolic Ca(2+) elevation, which is critical for T-cell activation. We previously showed that in activated T cells, Ca(2+) clearance is inhibited by the endoplasmic reticulum Ca(2+) sensor stromal interacting molecule 1 (STIM1) via association with the plasma membrane Ca(2+)/ATPase 4 (PMCA4) Ca(2+) pump. Having further observed that expression of both proteins is increased in activated T cells, the current study focused on mechanisms regulating both up-regulation of STIM1 and PMCA4 and assessing how this up-regulation contributes to control of Ca(2+) clearance...
August 15, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yang Ma, Chen-Chen Han, Yifan Li, Yang Wang, Wei Wei
Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) produced by hepatocellular carcinoma (HCC) cells are responsible for the growth of HCC cells. Accumulating evidence shows that insulin-like growth factor-binding protein-3 (IGFBP-3) suppresses HCC cell proliferation in both IGF-dependent and independent manners. It's unknown, however, whether treatment with exogenous IGFBP-3 inhibits bFGF and PDGF production in HCC cells. The present study demonstrates that IGFBP-3 suppressed IGF-1-induced bFGF and PDGF expression while it does not affect their expression in the absence of IGF-1...
September 16, 2016: Biochemical and Biophysical Research Communications
Dongmei Wang, Ellen S Mitchell
Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats...
2016: PloS One
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