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Jung Sun Min, Jin Chul Kim, Ji Ae Kim, Inho Kang, Jeong Keun Ahn
SIRT2, a member of the class III histone deacetylase family, has been identified as a tumor suppressor, which is associated with various cellular processes including metabolism and proliferation. However, the effects of SIRT2 on cancer cell migration caused by cytoskeletal rearrangement remain uncertain. Here we show that SIRT2 inhibits cell motility by suppressing actin polymerization. SIRT2 regulates actin dynamics through HSP90 destabilization and subsequent repression of LIM kinase (LIMK) 1/cofilin pathway...
June 13, 2018: Biochimica et Biophysica Acta
Vladislav Dolgachev, Sreehari Panicker, Sanjay Balijepalli, Lane Kelly McCandless, Yue Yin, Samantha Swamy, M V Suresh, Matthew J Delano, Mark R Hemmila, Krishnan Raghavendran, David Machado-Aranda
Previously, we reported that electroporation-mediated (EP) delivery of the FER gene improved survival in a combined trauma-pneumonia model. The mechanism of this protective effect is unknown. In this paper, we performed a pneumonia model in C57/BL6 mice with 500 CFU of Klebsiella pneumoniae. After inoculation, a plasmid encoding human FER was delivered by EP into the lung (PNA/pFER-EP). Survival of FER-treated vs. controls (PNA; PNA/EP-pcDNA) was recorded. In parallel cohorts, bronchial alveolar lavage (BAL) and lung were harvested at 24 and 72 h with markers of infection measured...
June 15, 2018: Gene Therapy
Yang Yang, Kenza Mamouni, Xin Li, Yanhua Chen, Sravan Kavuri, Yuhong Du, Haian Fu, Omer Kucuk, Daqing Wu
Docetaxel resistance remains a major obstacle in the treatment of prostate cancer (PCa) bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of PCa in preclinical models. DRD2 is ubiquitously expressed in PCa cell lines, and DRD2 is significantly reduced in PCa tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in PCa cells, but effectively induces cell cycle arrest...
June 15, 2018: Molecular Cancer Therapeutics
Kunal Nepali, Sunil Kumar, Hsiang-Ling Huang, Fei-Chiao Kuo, Cheng-Hsin Lee, Ching-Chuan Kuo, Teng-Kuang Yeh, Yu-Hsuan Li, Jang-Yang Chang, Jing-Ping Liou, Hsueh-Yun Lee
Correction for '2-Aroylquinoline-5,8-diones as potent anticancer agents displaying tubulin and heat shock protein 90 (HSP90) inhibition' by Kunal Nepali et al., Org. Biomol. Chem., 2016, 14, 716-723.
June 15, 2018: Organic & Biomolecular Chemistry
Jiayao Yu, Yi Li, Tian Wang, Xiang Zhong
This study was conducted to investigate effect of N6-methyladenosine (m6A) RNA methylation on Heat shock proteins (HSPs) and dissect the profile of HSP RNA methylation. The results showed that m6A methyltransferases METTL3 mRNA was decreased in responses to heat shock stress in HepG2 cells, but m6A-specific binding protein YTHDF2 mRNA was upregulated in a manner similar to HSP70 induction. Immunofluorescence staining showed that the majority of YTHDF2 was present in the cytosol, however, nearly all YTHDF2 translocated from the cytosol into the nucleus after heat shock...
2018: PloS One
ArunSundar MohanaSundaram, Thukani Sathanantham Shanmugarajan, Velayutham Ravichandiran
Cognitive impulsivity, a form of suboptimal cost-benefit decision making is an illustrious attribute of an array of neurodegenerative diseases including Alzheimer's Disease (AD). In this study, delay discounting paradigm was used to assess the effect of 3,4-dihydroxyphenylethanol (DOPET) on cognitive impulsivity-in an oA42i (oligomeric amyloid β1-42 plus ibotenic acid) induced AD mouse model-using a non-spatial T-maze task. The results depicted that oA42i administration elevated cognitive impulsivity, whereas DOPET treatment attenuated the impulsive behavior and matched the choice of the sham-operated controls...
June 14, 2018: ACS Chemical Neuroscience
Kuan Chai, Xuerao Ning, Thảo Thi Thanh Nguyễn, Boya Zhong, Takao Morinaga, Zhihan Li, Masato Shingyoji, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Naoto Yamaguchi, Masatoshi Tagawa
Heat shock protein 90 (HSP90) inhibitors suppressed MDM4 functions which mediated p53 ubiquitination, and blocked a chaperon function which influenced expression of the client proteins. We examined cytotoxic effects of the inhibitors, 17-allylamino-17-demetheoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), on mesothelioma and investigated combinatory effects of the inhibitors and adenoviruses expressing the wild-type p53 gene (Ad-p53). A majority of mesothelioma lacks p14 and p16 expression, which leads to defective p53 pathway despite bearing the wild-type p53 genotype...
May 25, 2018: Oncotarget
Sebastian N Politis, David Mazurais, Arianna Servili, Jose-Luis Zambonino-Infante, Joanna J Miest, Jonna Tomkiewicz, Ian A E Butts
European eel (Anguilla anguilla) is a euryhaline species, that has adapted to cope with both, hyper- and hypo-osmotic environments. This study investigates the effect of salinity, from a morphological and molecular point of view on European eel larvae reared from 0 to 12 days post hatch (dph). Offspring reared in 36 practical salinity units (psu; control), were compared with larvae reared in six scenarios, where salinity was decreased on 0 or 3 dph and in rates of 1, 2 or 4 psu/day, towards iso-osmotic conditions...
2018: PloS One
Xue-Jie Guo, Ji-Nian Feng
Heat shock proteins (Hsps) are prominent proteins that greatly contribute to insect survival under stress conditions. In this study, we cloned two Hsp transcripts (Aohsp70 and Aohsp90) from the grass thrip, Anaphothrips obscurus (Müller) (Thysanoptera: Thripidae), which is a polymorphic winged pest of corn and wheat. The cDNA sequences of Aohsp70 and Aohsp90 are 2382 and 2504 bp long, and encode proteins with calculated molecular weights of 70.02 kDa and 83.40 kDa, respectively. Aohsp90 was highly expressed in adults of both brachypters and macropters...
May 1, 2018: Journal of Insect Science
Shuyue Wang, Xu Li, Tingting Li, Huizhen Wang, Xiangchao Zhang, Jiarun Lou, Qiang Xing, Xiaoli Hu, Zhenmin Bao
The 94-kDa glucose-regulated protein (GRP94) belonging to the HSP90 family is an endoplasmic reticulum (ER) chaperone. It plays critical roles in ER quality control, and has been implicated as a specialized immune chaperone to regulate both innate and adaptive immunity. In this study, we identified and characterized a GRP94 gene (PyGRP94) from Yesso scallop (Patinopecten yessoensis). The protein sequence of PyGRP94 is highly conserved with its homologs in vertebrates, with a signal sequence in N-terminal, an ER retrieval signal sequence in C-terminal and a HATPase_c domain...
June 9, 2018: Fish & Shellfish Immunology
Jonathan J Sabbagh, Ricardo A Cordova, Dali Zheng, Marangelie Criado-Marrero, Andrea Lemus, Pengfei Li, Jeremy D Baker, Bryce A Nordhues, April L Darling, Carlos Martinez-Licha, Daniel A Rutz, Shreya Patel, Johannes Buchner, James W Leahy, John Koren, Chad A Dickey, Laura J Blair
Genetic and epigenetic alterations in FK506-binding protein 5 (FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). These variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we report that depletion of FKBP51 from the GR/90kDa heat shock protein (Hsp90) complex increased GR signaling in vivo...
June 12, 2018: ACS Chemical Biology
Mahammed Moniruzzaman, Indranath Ghosal, Debjit Das, Suman Bhusan Chakraborty
BACKGROUND: Improper control on reactive oxygen species (ROS) elimination process and formation of free radicals causes tissue dysfunction. Pineal hormone melatonin is considered a potent regulator of such oxidative damage in different vertebrates. Aim of the current communication is to evaluate the levels of oxidative stress and ROS induced damage, and amelioration of oxidative status through melatonin induced activation of signaling pathways. Hepatocytes were isolated from adult Labeo rohita and exposed to H2 O2 at three different doses (12...
June 11, 2018: Biological Research
Man-Gang Lee, Yi-Chang Liu, Yi-Lun Lee, Mohamed El-Shazly, Kuei-Hung Lai, Shou-Ping Shih, Seng-Chung Ke, Ming-Chang Hong, Ying-Chi Du, Juan-Cheng Yang, Ping-Jyun Sung, Zhi-Hong Wen, Mei-Chin Lu
Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, heteronemin exhibited potent cytotoxic effect against LNcap and PC3 prostate cancer cells with IC50 1.4 and 2.7 μM after 24 h, respectively...
June 10, 2018: Marine Drugs
Elisabetta Mileo, Marianne Ilbert, Alessandro Barducci, Patricia Bordes, Marie-Pierre Castanié-Cornet, Cyrille Garnier, Pierre Genevaux, Reynald Gillet, Pierre Goloubinoff, Françoise Ochsenbein, Gilbert Richarme, Chantal Iobbi-Nivol, Marie-Thérèse Giudici-Orticoni, Brigitte Gontero, Olivier Genest
The "Bioénergétique et Ingénierie des Protéines (BIP)" laboratory, CNRS (France), organized its first French workshop on molecular chaperone proteins and protein folding in November 2017. The goal of this workshop was to gather scientists working in France on chaperone proteins and protein folding. This initiative was a great success with excellent talks and fruitful discussions. The highlights were on the description of unexpected functions and posttranslational regulation of known molecular chaperones (such as Hsp90, Hsp33, SecB, GroEL) and on state-of-the-art methods to tackle questions related to this theme, including Cryo-electron microscopy, Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR), simulation and modeling...
June 8, 2018: Biochimie
Cheng Qu, Ran Wang, Wunan Che, Xun Zhu, Fengqi Li, Chen Luo
Harmonia axyridis (Coleoptera: Coccinellidae) is a polyphagous insect that is an important biological agent used to control agricultural and forestry pests. The role of functional genes in H. axyridis based on quantitative real-time PCR (qRT-PCR) is increasingly well understood to investigate biology, physiology, feeding behavior and the role of important genes in physiological processes. Quantitative real-time PCR (qRT-PCR) is a powerful and reliable technique to quantify gene expression. Using qRT-PCR, expression levels of target genes are determined based on the levels of internal reference genes; therefore, reference genes need to be stably expressed under specific experimental conditions...
2018: PloS One
Jieli Pan, Fusheng Jiang, Jia Zhou, Dehong Wu, Zhenhua Sheng, Meiya Li
Lung cancer is one of the leading causes of cancer-related death in the world. MicroRNA- (miR-) 628-3p plays critical roles in many cancers, including lung cancer. We investigated how miR-628-3p affected migration and apoptosis in A549 cells. We used bioinformatics algorithms to predict the miR-628-3p target gene to study the molecular mechanism by which miR-628-3p contributes to lung cancer. Then, we used the luciferase reporter assay to identify whether heat shock protein 90a (HSP90) is a direct target of miR-628-3p...
2018: BioMed Research International
Heike Fuhrmann-Stroissnigg, Laura J Niedernhofer, Paul D Robbins
Aging is characterized by progressive decay of biological systems and although it is not considered a disease, it is one of the main risk factors for chronic diseases and many types of cancers. The accumulation of senescent cells in various tissues is thought to be a major factor contributing to aging and age-related diseases. Removal of senescent cells during aging by either genetic or therapeutic methods have led to an improvement of several age related disease in mice. In this preview, we highlight the significance of developing senotherapeutic approaches to specifically kill senescent cells (senolytics) or suppress the senescence-associated secretory phenotype (SASP) that drives sterile inflammation (senomorphics) associated with aging to extend healthspan and potentially lifespan...
June 9, 2018: Cell Cycle
Cao Zhou, Hong Yang, Zhao Wang, Gui-Yun Long, Dao-Chao Jin
White-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), one of the main agricultural insect pests in China, is resistant to a wide variety of insecticides. We used transcriptome analysis to compare the expression patterns of resistance- and stress-response genes in S. furcifera subjected to imidacloprid, deltamethrin, and triazophos stress, to determine the molecular mechanisms of resistance to these insecticides. A comparative analysis of gene expression under imidacloprid, deltamethrin, and triazophos stress revealed 1,123, 841, and 316 upregulated unigenes, respectively, compared to the control...
June 8, 2018: Scientific Reports
Baosheng Chen, Mark S Longtine, Joan K Riley, D Michael Nelson
INTRODUCTION: There is a need for prophylaxis to reduce placental-associated intrauterine growth restriction (IUGR). Pomegranate juice (PJ) is replete with phytochemicals having biological effects at non-pharmacological concentrations. We test the hypothesis that exposure of pregnant mice to hypoxia late in gestation induces cellular stress in the placenta, which can be ameliorated by antecedent maternal consumption of PJ. MATERIALS AND METHODS: We exposed pregnant mice to 12% or 21% oxygen, with food ad libitum or restricted, and with consumption of PJ or glucose between 12...
June 2018: Placenta
Félix Sauvage, Elias Fattal, Walhan Al-Shaer, Stéphanie Denis, Emilie Brotin, Christophe Denoyelle, Cécile Blanc-Fournier, Balthazar Toussaint, Samir Messaoudi, Mouad Alami, Gillian Barratt, Juliette Vergnaud-Gauduchon
In this study, we investigated the anticancer efficacy of pegylated liposomes containing 6BrCaQ, an hsp90 inhibitor derived from novobiocin. 6BrCaQ has been previously identified as the most potent compound in a series of quinoleic novobiocin analogs but is poorly water-soluble. We investigated, for the first time, the anti-proliferative effects of this drug in vivo in an orthotopic breast cancer model (MDA-MB-231 luc) using pegylated liposomes to allow its administration. Hsp90, hsp70 and hsp27 protein and mRNA expressions were not strongly affected after treatment meaning it did not induce a heat shock response often associated with resistance and poor prognosis...
June 5, 2018: Cancer Letters
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