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Olivier Poupel, Caroline Proux, Bernd Jagla, Tarek Msadek, Sarah Dubrac
The success of Staphylococcus aureus, as both a human and animal pathogen, stems from its ability to rapidly adapt to a wide spectrum of environmental conditions. Two-component systems (TCSs) play a crucial role in this process. Here, we describe a novel staphylococcal virulence factor, SpdC, an Abi-domain protein, involved in signal sensing and/or transduction. We have uncovered a functional link between the WalKR essential TCS and the SpdC Abi membrane protein. Expression of spdC is positively regulated by the WalKR system and, in turn, SpdC negatively controls WalKR regulon genes, effectively constituting a negative feedback loop...
March 2018: PLoS Pathogens
Xiaoli Wang, Wei Xiong, Yiyin Tang
Breast cancer is one of the most common metastatic tumor types. Reports have suggested that Tunicamycin may inhibit the aggressiveness of cancer cells by promoting their apoptosis. In the present study, the inhibitory effects of Tunicamycin were investigated and the potential molecular mechanism underlying the Tunicamycin-inhibited growth and aggressiveness of breast cancer cells was explored. In vitro assays demonstrated that Tunicamycin significantly inhibited growth and arrested the cell cycle of breast cancer cells in a dose-dependent manner, compared with control cells...
April 2018: Oncology Letters
Wen-Jun Yan, Ruo-Bin Liu, Ling-Kai Wang, Ya-Bing Ma, Shao-Li Ding, Fei Deng, Zhong-Yuan Hu, Da-Bin Wang
Endoplasmic reticulum (ER) stress occurring in stringent conditions is critically involved in neuronal survival and death. Resveratrol is a non-flavonoid polyphenol that has neuroprotective effects against many neurological disorders. Here, we investigated the potential protective effects of resveratrol in an in vitro ER stress model mimicked by tunicamycin (TM) treatment in neuronal HT22 cells. We found that TM dose-dependently decreased cell viability and increased apoptosis, which were both significantly attenuated by resveratrol treatment...
2018: Frontiers in Neuroscience
Wen-Tai Chiu, Heng-Ai Chang, Yi-Hsin Lin, Yu-Shan Lin, Hsiao-Tzu Chang, Hsi-Hui Lin, Soon-Cen Huang, Ming-Jer Tang, Meng-Ru Shen
Ca2+ plays a significant role in linking the induction of apoptosis. The key anti-apoptotic protein, Bcl-2, has been reported to regulate the movement of Ca2+ across the ER membrane, but the exact effect of Bcl-2 on Ca2+ levels remains controversial. Store-operated Ca2+ entry (SOCE), a major mode of Ca2+ uptake in non-excitable cells, is activated by depletion of Ca2+ in the ER. Depletion of Ca2+ in the ER causes translocation of the SOC channel activator, STIM1, to the plasma membrane. Thereafter, STIM1 binds to Orai1 or/and TRPC1 channels, forcing them to open and thereby allow Ca2+ entry...
December 2018: Cell Death Discovery
Antonello Storniolo, Vincenzo Alfano, Sabino Carbotta, Elisabetta Ferretti, Livia Di Renzo
Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase...
December 2018: Cell Death Discovery
Mitchell R K L Lie, Janine van der Giessen, Gwenny M Fuhler, Alison de Lima, Maikel P Peppelenbosch, Cokkie van der Ent, C Janneke van der Woude
BACKGROUND: Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. METHODS: Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment...
March 9, 2018: Journal of Translational Medicine
Myong-Min Lee, Hyeong-Geug Kim, Sung-Bae Lee, Jin-Seok Lee, Won-Yong Kim, Seung-Hoon Choi, Sam-Keun Lee, Chang-Kyu Byun, Pung-Mi Hyun, Chang-Gue Son
BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has increased by 15-39% worldwide, but no pharmaceutical therapeutics exists. HYPOTHESIS/PURPOSE: This study investigated anti-hepatosteatotic effect of CGplus (a standardized herbal composition of Artemisia iwayomogi, Amomum xanthioides, and Salvia miltiorrhiza) and its underlying mechanisms in a tunicamycin-induced NASH model. METHODS: C57/BL6J male mice were orally administrated CGplus (50, 100, or 200 mg/kg), dimethyl dimethoxy biphenyl dicarboxylate (DDB, 50 mg/kg) or distilled water daily for 5 days...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Fang-Yuan Gong, Zheng Gong, Cui-Cui Duo, Jun Wang, Chao Hong, Xiao-Ming Gao
Calreticulin (CRT), a luminal resident calcium-binding glycoprotein of the cell, is a tumor-associated antigen involved in tumorigenesis and also an autoantigen targeted by autoantibodies found in patients with various autoimmune diseases. We have previously shown that prokaryotically expressed recombinant murine CRT (rCRT) exhibits strong stimulatory activities against monocytes/macrophages in vitro and potent immunogenicity in vivo, which is partially attributable to self-oligomerization of soluble rCRT. However, even in oligomerized form native CRT (nCRT) isolated from mouse liver is much less active than rCRT, arguing against the possibility that self-oligomerization alone would license potent pro-inflammatory properties to nCRT...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xuemei Wan, Jeffrey D Serrill, Ian R Humphreys, Michelle Tan, Kerry L McPhail, Ian G Ganley, Jane E Ishmael
Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces mTOR-independent autophagy as an adaptive stress response that precedes cell death. Autophagy-related (ATG) protein 5 (ATG5) is required for coibamide-induced autophagy but not required for coibamide-induced apoptosis. Using wild-type and autophagy-deficient mouse embryonic fibroblasts (MEFs) we demonstrate that coibamide-induced toxicity is delayed in ATG5-/- cells relative to ATG5+/+ cells...
March 1, 2018: Marine Drugs
Chloé Sauzay, Christophe Louandre, Sandra Bodeau, Frédéric Anglade, Corinne Godin, Zuzana Saidak, Jean-Xavier Fontaine, Cédric Usureau, Nathalie Martin, Roland Molinie, Julie Pascal, François Mesnard, Olivier Pluquet, Antoine Galmiche
Sorafenib is the first line treatment for advanced hepatocellular carcinoma (HCC). We explored its impact on the proteostasis of cancer cells, i.e. the processes that regulate the synthesis, maturation and turn-over of cellular proteins. We observed that sorafenib inhibits the production of the tumour marker alpha-foetoprotein (AFP) in two different HCC cell lines, an effect that correlated with a radical inhibition of protein biosynthesis. This effect was observed at clinically relevant concentrations of sorafenib and was not related to the effect of sorafenib on the transport of amino acids across the plasma membrane or the induction of the unfolded protein response (UPR)...
February 2, 2018: Oncotarget
Takashi Ito, Yukiko Nakanishi, Noriko Yamaji, Shigeru Murakami, Stephen W Schaffer
It has been identified that skeletal muscle is an endocrine tissue. Since skeletal muscle aging affects not only to muscle strength and function but to systemic aging and lifespan, myokines secreted from skeletal muscle may be crucial factors for intertissue communication during aging. In the present study, we investigated the expression of myokines associated with skeletal muscle aging in taurine transporter knockout (TauTKO) mice, which exhibit the accelerated skeletal muscle aging. Among transforming growth factor (TGF)-beta family genes, only growth and differentiation factor 15 (GDF15) was markedly higher (>3-fold) in skeletal muscle of old TauTKO mice compared with that of either young TauTKO mice or old wild-type mice...
2018: Biological & Pharmaceutical Bulletin
Yu Bo, Jiang Kaibiao, Zhang Jidong
Osteosarcoma is one of the most common malignant tumors in adolescent populations and the prognosis remains incompletely understand. Previous reports have demonstrated that microRNA‑124 (miR‑124) has inhibitory effects on various human malignancies and is associated with tumor progression. However, the clinical significance and potential mechanisms of miR‑124 in the progression of osteosarcoma is not clearly understood. In this study, the potential molecular mechanism of miR‑124 in osteosarcoma tumorigenesis, growth and aggressiveness was investigated...
February 27, 2018: Molecular Medicine Reports
Esther González-Almela, Hugh Williams, Miguel A Sanz, Luis Carrasco
Animal viruses have evolved a variety of strategies to ensure the efficient translation of their mRNAs. One such strategy is the use of internal ribosome entry site (IRES) elements, which circumvent the requirement for some eukaryotic initiation factors (eIFs). Much effort has been directed to unravel the precise mechanism of translation initiation by hepatitis C virus (HCV) mRNA. In the present study, we examined the involvement of several eIFs in HCV IRES-driven translation in human cells in a comparative analysis with mRNAs bearing the encephalomyocarditis virus or the Cricket paralysis virus IRES element...
2018: Frontiers in Microbiology
Man Liu, Guangbin Shi, Anyu Zhou, Cassady E Rupert, Kareen L K Coulombe, Samuel C Dudley
RATIONALE: Heart failure is characterized by electrical remodeling that contributes to arrhythmic risk. The unfolded protein response (UPR) is active in heart failure and can decrease protein levels by increasing mRNA decay, accelerating protein degradation, and inhibiting protein translation. OBJECTIVE: Therefore, we investigated whether the UPR downregulated cardiac ion channels that may contribute to arrhythmogenic electrical remodeling. METHODS: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study cardiac ion channels...
February 21, 2018: Journal of Molecular and Cellular Cardiology
Freddy Romero, Xu Hong, Dilip Shah, Caleb B Kallen, Ivan Rosas, Zhi Guo, DeLeila Schriner, Julie Barta, Hoora Shaghaghi, Jan B Hoek, Clementina Mesaros, Augustine M Choi, Nathaniel W Snyder, Ross Summer
RATIONALE: Endoplasmic reticulum stress is evident in the alveolar epithelium of humans and mice with pulmonary fibrosis but neither the mechanisms causing ER stress nor its contribution to fibrosis are understood. A well-recognized adaptive response to ER stress is that affected cells induce lipid synthesis; however, we recently reported that lipid synthesis was downregulated in the alveolar epithelium in pulmonary fibrosis. OBJECTIVES: To determine whether lipid synthesis is needed to resolve ER stress and limit fibrotic remodeling in the lung...
February 21, 2018: American Journal of Respiratory Cell and Molecular Biology
Christoph H R Senges, Arwa Al-Dilaimi, Douglas H Marchbank, Daniel Wibberg, Anika Winkler, Brad Haltli, Minou Nowrousian, Jörn Kalinowski, Russell G Kerr, Julia E Bandow
Actinomycetes are known for producing diverse secondary metabolites. Combining genomics with untargeted data-dependent tandem MS and molecular networking, we characterized the secreted metabolome of the tunicamycin producer Streptomyces chartreusis NRRL 3882. The genome harbors 128 predicted biosynthetic gene clusters. We detected >1,000 distinct secreted metabolites in culture supernatants, only 22 of which were identified based on standards and public spectral libraries. S. chartreusis adapts the secreted metabolome to cultivation conditions...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jiho Yoo, Ellene H Mashalidis, Alvin C Y Kuk, Kazuki Yamamoto, Benjamin Kaeser, Satoshi Ichikawa, Seok-Yong Lee
N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders. The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin. Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT...
February 19, 2018: Nature Structural & Molecular Biology
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Changwon Yang, Whasun Lim, Hyocheol Bae, Fuller W Bazer, Gwonhwa Song
C-C motif chemokine ligand 2 (CCL2) is a small chemokine which belongs to the CC-type chemokine family, and has chemoattractant activity for recruitment of monocytes to sites of inflammation. Overexpressed CCL2 binding to its receptor C-C chemokine receptor 2 increases the risk of breast cancer in humans, but its effects on proliferation of bovine mammary epithelial cells is not known. Maintaining a high level of proliferative activity in bovine mammary epithelial cells during lactation is important for improving milk yield and can benefit the dairy industry economically...
February 14, 2018: Journal of Dairy Science
Ke Du, Mingyan Liu, Xin Zhong, Weifan Yao, Qinghuan Xiao, Quan Wen, Bo Yang, Minjie Wei
SCOPE: We investigated the role of endoplasmic reticulum (ER) stress in the protective effects of EGCG against the neuronal apoptosis in Aβ 1-42 -induced SH-SY5Y cells and APP/PS1 transgenic mice. METHODS AND RESULTS: Cell viability (CCK8 assay), flow cytometry, Hoechst 33258 staining, immunohistochemistry, Transmission Electron Microscopy (TEM), western blotting were used. EGCG prevented Aβ1-42-induced toxicity in SH-SY5Y cells, increased cell viability and decreased apoptosis in a dose-dependent manner...
February 15, 2018: Molecular Nutrition & Food Research
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