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Hsp90 cell wall

Claudia Göttlich, Meik Kunz, Cornelia Zapp, Sarah L Nietzer, Heike Walles, Thomas Dandekar, Gudrun Dandekar
Patient-tailored therapy based on tumor drivers is promising for lung cancer treatment. For this we combined in vitro tissue models with in silico analyses. Using individual cell lines with specific mutations we demonstrate a generic and rapid stratification pipeline for targeted tumor therapy. We improve in vitro models of tissue-conditions by a biological matrix-based three-dimensional (3D) tissue culture that allows in vitro drug testing: it correctly shows a strong drug response upon gefitinib treatment in a cell line harboring an EGFR activating mutation (HCC827), but no clear drug response upon treatment with the HSP90 inhibitor 17AAG in two cell lines with KRAS mutations (H441, A549)...
May 24, 2018: Molecular Oncology
Tavia Caplan, Elizabeth J Polvi, Jinglin L Xie, Shoshana Buckhalter, Michelle D Leach, Nicole Robbins, Leah E Cowen
Candida albicans is a leading cause of death due to fungal infection. Treatment of systemic candidiasis often relies on echinocandins, which disrupt cell wall synthesis. Resistance is readily acquired via mutations in the drug target gene, FKS1. Both basal tolerance and resistance to echinocandins require cellular stress responses. We performed a systematic analysis of 3,030 C. albicans mutants to define circuitry governing cellular responses to echinocandins. We identified 16 genes for which deletion or transcriptional repression enhanced echinocandin susceptibility, including components of the Pkc1-MAPK signaling cascade...
May 22, 2018: Cell Reports
Pramod P Mehta, Pei-Pei Kung, Shinji Yamazaki, Marlena Walls, Andrea Shen, Leslie Nguyen, Michael R Gehring, Gerrit Los, Tod Smeal, Min-Jean Yin
No abstract text is available yet for this article.
May 28, 2018: Cancer Letters
Laiqiang Gao, Haiying Wang, Xuehong Wang, Ailan Li, Qiang Ma
Candida albicans, a human fungal pathogen, is able to tolerate certain levels of environmental stresses. Its cell wall plays an important role in cellular homeostasis, responding to environmental stimuli. SRB1 gene encodes a GDP-mannose pyrophosphorylase that catalyzes the formation of the major cell wall component, mannan. The exact relationship between SRB1 and various stresses is not yet fully understood. In current study, C. albicans SC5314 cells were exposed to oxidative, hyperosmotic, and thermal stresses...
February 14, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Bekir Mustafa Yoğurtçu, Selami Demirci, Ayşegül Doğan, Ayla Burçin Asutay, Fikrettin Şahin
Invasive fungal infections are one of the major challenges especially for immunosuppressed patients since they are drug resistant and pathogen to patients. Therefore, developing new, efficient and nonresistant antifungal agents have been a primary focus of international research. In the current study, a novel Schiff base [hetero-dinuclear copper(II) Mn(II) complex] (SB) derivative was investigated for its anticandidal activity against Candida albicans and possible mechanisms inducing cell death. The results revealed that SB treatment induces apoptotic and necrotic pathways in C...
October 27, 2017: World Journal of Microbiology & Biotechnology
Ning Zhang, Lingran Zhang, Lei Zhao, Yan Ren, Dangqun Cui, Jianhui Chen, Yongyan Wang, Pengbo Yu, Feng Chen
By comparing the differentially accumulated proteins from the derivatives (UC 1110 × PI 610750) in the F10 recombinant inbred line population which differed in cold-tolerance, altogether 223 proteins with significantly altered abundance were identified. The comparison of 10 cold-sensitive descendant lines with 10 cold-tolerant descendant lines identified 140 proteins that showed decreased protein abundance, such as the components of the photosynthesis apparatus and cell-wall metabolism. The identified proteins were classified into the following main groups: protein metabolism, stress/defense, carbohydrate metabolism, lipid metabolism, sulfur metabolism, nitrogen metabolism, RNA metabolism, energy production, cell-wall metabolism, membrane and transportation, and signal transduction...
August 8, 2017: Scientific Reports
Sharanya Chatterjee, Utpal Tatu
BACKGROUND: Thermotolerance is an essential attribute for pathogenesis of Cryptococcus as exemplified by the fact that only two species in the genus, which can grow at 37°C, are human pathogens. Species which have other virulence factors including capsule formation and melanisation, but lack the ability to propagate at 37°C are not pathogenic. In another related fungal pathogen, Candida albicans, heat shock protein 90 has been implicated to be a central player in commanding pathogenicity by governing yeast to hyphal transition and drug resistance...
August 2017: PLoS Neglected Tropical Diseases
Li-Chu Ong, Yuen-Fen Tan, Boon Shing Tan, Felicia Fei-Lei Chung, Soon-Keng Cheong, Chee-Onn Leong
Single-walled carbon nanotubes (SWCNTs) are carbon-based nanomaterials that possess immense industrial potential. Despite accumulating evidence that exposure to SWCNTs might be toxic to humans, our understanding of the mechanisms for cellular toxicity of SWCNTs remain limited. Here, we demonstrated that acute exposure of short (1-3μm) and regular-length (5-30μm) pristine, carboxylated or hydroxylated SWCNTs inhibited cell proliferation in human somatic and human stem cells in a cell type-dependent manner...
August 15, 2017: Toxicology and Applied Pharmacology
Cleber Fernando Serafin, Ana Paula Paris, Claudete Rodrigues Paula, Rita Cássia Garcia Simão, Rinaldo Ferreira Gandra
This study evaluated the effect of the antiretroviral ritonavir on protease secretion in different strains of Cryptococcus neoformans isolated from the environment and investigated the expression of heat shock protein (Hsp90), classically described virulence factors in other yeast in the presence of the same antiretroviral. The presence of the enzyme was detected by the formation of a degradation of the halo around the colonies. The results were classified as follows: level 1 (without proteases), level 2 (positive for proteases), and level 3 (strongly positive for proteases)...
April 2017: Microbial Ecology
Lixia Zheng, Shao Wu, Li Tan, Huo Tan, Baodan Yu
Delivery of amphiphobic drugs (insoluble in both water and oil) has been a great challenge in drug delivery. SNX-2112, a novel inhibitor of Hsp90, is a promising drug candidate for treating various types of cancers; however, the insolubility greatly limits its clinical application. This study aimed to build a new type of drug delivery system using single-walled carbon nanotubes (SWNTs) for controllable release of SNX-2112; chitosan (CHI) was non-covalently added to SWNTs to improve their biocompatibility. SWNTs-CHI demonstrated high drug-loading capability; the release of SNX-2112 was pH triggered and time related...
September 2016: Journal of Biomaterials Applications
Michael C Hsu, Charles N Weber, Mustafa A Mohammed, Terence P Gade, Stephen Hunt, Gregory J Nadolski, Timothy W I Clark
PURPOSE: To characterize thermal changes induced by rheolytic thrombectomy (RT) within an ex vivo venous model and evaluate resultant changes of endothelial and vessel wall injury. MATERIALS AND METHODS: Patent human saphenous vein segments without thrombus were mounted in an ex vivo perfusion system with a temperature probe apposed to the adventitial surface. RT was performed over a guide wire to facilitate device centering. Continuous RT was performed for 4 minutes with temperature recorded every 10 seconds...
June 2016: Journal of Vascular and Interventional Radiology: JVIR
Felipe Souto Araújo, Luciene Melo Coelho, Lívia do Carmo Silva, Benedito Rodrigues da Silva Neto, Juliana Alves Parente-Rocha, Alexandre Melo Bailão, Cecília Maria Alves de Oliveira, Gabriel da Rocha Fernandes, Orville Hernández, Juan Guillermo McEwen Ochoa, Célia Maria de Almeida Soares, Maristela Pereira
Paracoccidioides spp., a dimorphic pathogenic fungus, is the etiologic agent of paracoccidioidomycosis (PCM). PCM is an endemic disease that affects at least 10 million people in Latin America, causing severe public health problems. The drugs used against pathogenic fungi have various side effects and limited efficacy; therefore, there is an inevitable and urgent medical need for the development of new antifungal drugs. In the present study, we evaluated the transcriptional profile of Paracoccidioides lutzii exposed to argentilactone, a constituent of the essential oil of Hyptis ovalifolia...
January 2016: PLoS Neglected Tropical Diseases
K J A McCullagh, R Cooney, T O'Brien
Endothelial nitric oxide synthase (eNOS) is the major source of nitric oxide (NO) production in blood vessels. One of the pleitropic functions of eNOS derived NO is to inhibit vascular smooth muscle cell proliferation in the blood vessel wall, and whose dysfunction is a primary cause of atherosclerosis and restenosis. In this study there was an interest in examining the gene profile of eNOS adenoviral (Ad-eNOS) transduced human coronary artery smooth muscle cells (HCASMC) to further understand the eNOS inhibitory effect on smooth muscle cell proliferation...
January 30, 2016: Nitric Oxide: Biology and Chemistry
Muhammad A Farooq, Rafaqat A Gill, Basharat Ali, Jian Wang, Faisal Islam, Shafaqat Ali, Weijun Zhou
Arsenic (As) is an environmental toxin pollutant that affects the numerous physiological processes of plants. In present study, two Brassica napus L. cultivars were subjected to various concentrations (0, 50, 100, and 200 µM) of As for 14 days, plants were examined for As subcellular distribution, photosynthesis parameters, oxidative stress, and ultrastructural changes under As-stress. Differential fraction analysis showed that significant amount of As was accumulated in the cell wall as compared to other organelles...
March 2016: Ecotoxicology
William J Steinbach, Frédéric Lamoth, Praveen R Juvvadi
The antifungal "paradoxical effect" has been described as the reversal of growth inhibition at high doses of echinocandins, most usually caspofungin. This microbiological effect appears to be a cellular compensatory response to cell wall damage, resulting in alteration of cell wall content and structure as well as fungal morphology and growth. In vitro studies demonstrate this reproducible effect in a certain percentage of fungal isolates, but animal model and clinical studies are less consistent. The calcineurin and Hsp90 cell signaling pathways appear to play a major role in regulating these cellular and structural changes...
December 1, 2015: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Wei Zhang, Kou Liu, Jing Li, Jun Liang, Kuangfei Lin
Lead (Pb) and decabromodiphenyl ether (BDE209) are the mainly co-existed contaminants at e-waste recycling sites. The potential toxicity of Pb (250 μg g(-1)) to earthworm Eisenia fetida in the presence of BDE209 (1, 10 and 100 μg g(-1)) was determined during 14-d incubation period. Compared to Pb treatment alone, the co-exposure with 1 μg g(-1) BDE209 barely affected Pb uptake, subcellular partitioning and gene expression; however, histopathological changes in earthworms' body wall (epidermal, circular and longitudinal muscles) demonstrated that 10 and 100 μg g(-1) BDE209 additions enhanced Pb uptake and altered its subcellular partitioning, indicating that Pb redistributed from fractions E (cell debris) and D (metal-rich granules) to fraction C (cytosols); Additionally, BDE209 supply significantly inhibited (p<0...
December 30, 2015: Journal of Hazardous Materials
Frédéric Lamoth, Praveen R Juvvadi, William J Steinbach
Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation...
2015: Frontiers in Microbiology
Mirella Vazzana, Tiziana Siragusa, Vincenzo Arizza, Giuseppa Buscaino, Monica Celi
Wound repair is a key event in the regeneration mechanisms of echinoderms. We studied, at the behavioural, cellular and molecular levels, the wound healing processes in Holothuria tubulosa after injuries to the body wall. The experiments were performed for periods of up to 72 h, and various coelomocyte counts, as well as the expression of heat shock proteins (HS27, HSP70 and HSP90), were recorded. Dermal wound healing was nearly complete within 72 h. In the early stages, we observed the injured animals twisting their bodies to keep their injuries on the surface of the water for the extrusion of the buccal pedicles...
February 2015: Fish & Shellfish Immunology
Krystyna Teichert-Kuliszewska, James N Tsoporis, Jean-Francois Desjardins, Jun Yin, Liming Wang, Wolfgang M Kuebler, Thomas G Parker
AIMS: S100A1, a 10-kDa, Ca(2+)-binding protein, is expressed in endothelial cells (ECs) and binds eNOS. Its absence is associated with impaired production of nitric oxide (NO) and mild systemic hypertension. As endothelial dysfunction contributes to clinical and experimental pulmonary hypertension (PH), we investigated the impact of deleting S100A1 in mice, on pulmonary haemodynamics, endothelial function, NO production, associated signalling pathways, and apoptosis. METHODS AND RESULTS: Compared with wild-type (WT), S100A1-knock-out mice (KO) exhibited increased right ventricular (RV) weight/body weight ratio and elevated RV pressure in the absence of altered left ventricular filling pressures, accompanied by increase in wall thickness of muscularized pulmonary arteries and a reduction in microvascular perfusion...
January 1, 2015: Cardiovascular Research
Frédéric Lamoth, Praveen R Juvvadi, William J Steinbach
Invasive aspergillosis is a life-threatening and difficult to treat infection in immunosuppressed patients. The efficacy of current anti-Aspergillus therapies, targeting the cell wall or membrane, is limited by toxicity (polyenes), fungistatic activity and some level of basal resistance (echinocandins), or the emergence of acquired resistance (triazoles). The heat shock protein 90 (Hsp90) is a conserved molecular chaperone involved in the rapid development of antifungal resistance in the yeast Candida albicans...
2016: Critical Reviews in Microbiology
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