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Hsp90 cell wall

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
Michelle D Leach, Susan Budge, Louise Walker, Carol Munro, Leah E Cowen, Alistair J P Brown
Thermal adaptation is essential in all organisms. In yeasts, the heat shock response is commanded by the heat shock transcription factor Hsf1. Here we have integrated unbiased genetic screens with directed molecular dissection to demonstrate that multiple signalling cascades contribute to thermal adaptation in the pathogenic yeast Candida albicans. We show that the molecular chaperone heat shock protein 90 (Hsp90) interacts with and down-regulates Hsf1 thereby modulating short term thermal adaptation. In the longer term, thermal adaptation depends on key MAP kinase signalling pathways that are associated with cell wall remodelling: the Hog1, Mkc1 and Cek1 pathways...
December 2012: PLoS Pathogens
Kyoung-Hee Lee, Amlan Biswas, Yuen-Joyce Liu, Koichi S Kobayashi
The innate immune system serves as the first line of defense by detecting microbes and initiating inflammatory responses. Although both Toll-like receptor (TLR) and nucleotide binding domain and leucine-rich repeat (NLR) proteins are important for this process, their excessive activation is hazardous to hosts; thus, tight regulation is required. Endotoxin tolerance is refractory to repeated lipopolysaccharide (LPS) stimulation and serves as a host defense mechanism against septic shock caused by an excessive TLR4 response during gram-negative bacterial infection...
November 16, 2012: Journal of Biological Chemistry
Rebecca S Shapiro, Aimee K Zaas, Marisol Betancourt-Quiroz, John R Perfect, Leah E Cowen
The molecular chaperone Hsp90 orchestrates regulatory circuitry governing fungal morphogenesis, biofilm development, drug resistance, and virulence. Hsp90 functions in concert with co-chaperones to regulate stability and activation of client proteins, many of which are signal transducers. Here, we characterize the first Hsp90 co-chaperone in the leading human fungal pathogen, Candida albicans. We demonstrate that Sgt1 physically interacts with Hsp90, and that it governs C. albicans morphogenesis and drug resistance...
2012: PloS One
Frédéric Lamoth, Praveen R Juvvadi, Jarrod R Fortwendel, William J Steinbach
Heat shock protein 90 (Hsp90) is a eukaryotic molecular chaperone. Its involvement in the resistance of Candida albicans to azole and echinocandin antifungals is well established. However, little is known about Hsp90's function in the filamentous fungal pathogen Aspergillus fumigatus. We investigated the role of Hsp90 in A. fumigatus by genetic repression and examined its cellular localization under various stress conditions. Failure to generate a deletion strain of hsp90 suggested that it is essential. Genetic repression of Hsp90 was achieved by an inducible nitrogen-dependent promoter (pniiA-Hsp90) and led to decreased spore viability, decreased hyphal growth, and severe defects in germination and conidiation concomitant with the downregulation of the conidiation-specific transcription factors brlA, wetA, and abaA...
November 2012: Eukaryotic Cell
Nicholas D Beyda, Russell E Lewis, Kevin W Garey
OBJECTIVE: To summarize published data regarding mechanisms of reduced echinocandin susceptibility in Candida spp., the impact of echinocandin resistance on the fitness and virulence of Candida isolates, and current and future treatment approaches. DATA SOURCES: A search of MEDLINE databases (1966-September 2011) was conducted. STUDY SELECTION AND DATA EXTRACTION: Databases were searched using the terms echinocandin, resistance, and Candida...
July 2012: Annals of Pharmacotherapy
Sheena D Singh-Babak, Tomas Babak, Stephanie Diezmann, Jessica A Hill, Jinglin Lucy Xie, Ying-Lien Chen, Susan M Poutanen, Robert P Rennie, Joseph Heitman, Leah E Cowen
The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia...
2012: PLoS Pathogens
Carol A Munro
No abstract text is available yet for this article.
February 2012: Expert Review of Anti-infective Therapy
O Hernandez, A M Garcia, A J Almeida, D Tamayo, A Gonzalez, A Restrepo, J G McEwen
This study focuses on gene expression during crucial biological phenomena of the dimorphic fungal human pathogen Paracoccidioides brasiliensis, the conidia-to-yeast (C-Y) transition and the conidia-to-mycelia (C-M) germination. We studied 10 genes involved in different cellular functions: oxidative stress response (alternative oxidase (AOX), superoxide dismutase (SOD), flavodoxin, conserved hypothetical protein (Y20)); cell metabolism (glyceraldehyde-3-phosphate dehydrogenase (GADPH), cholestenol Delta-isomerase (ChDI), glycine dehydrogenase (GDh)) and heat shock response (Heat shock protein 90 (HSP90)), and cell synthesis and wall structure (glucan synthase-1 (GS-1), α-1,3-glucan synthase (αGS), and mannosyltransferase (MT))...
November 2011: Yeast
Weiming Ni, Alex H Hutagalung, Shumin Li, Henry F Epstein
The UNC-45 family of molecular chaperones is expressed in metazoan organisms from Caenorhabditis elegans to humans. The UNC-45 protein is essential in C. elegans for early body-wall muscle cell development and A-band assembly. We show that the myosin-binding UCS domain of UNC-45 alone is sufficient to rescue lethal unc-45 null mutants arrested in embryonic muscle development and temperature-sensitive loss-of-function unc-45 mutants defective in worm A-band assembly. Removal of the Hsp90-binding TPR domain of UNC-45 does not affect rescue...
September 15, 2011: Journal of Cell Science
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