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https://www.readbyqxmd.com/read/28334757/perturbations-in-cell-signaling-elicit-early-cardiac-defects-in-mucopolysaccharidosis-type-ii
#1
Roberto Costa, Andrea Urbani, Marika Salvalaio, Stefania Bellesso, Domenico Cieri, Ilaria Zancan, Mirella Filocamo, Paolo Bonaldo, Ildiko Szabò, Rosella Tomanin, Enrico Moro
Morphogens release and activity can be negatively affected by an impaired glycosaminoglycans (GAGs) turnover and proteoglycans assembly in the extracellular matrix, leading to altered tissue morphogenesis. In this work, we show that loss of Iduronate-2-sulfatase (IDS) activity, affecting GAGs catabolism and responsible for a life-threatening valvulopathy in mucopolysaccharidosis type II (MPSII), triggers early Sonic Hedgehog (Shh) and Wnt/β-catenin signaling defects, leading to aberrant heart development and atrioventricular valve formation in a zebrafish model...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334745/disease-correction-by-aav-mediated-gene-therapy-in-a-new-mouse-model-of-mucopolysaccharidosis-type-iiid
#2
Carles Roca, Sandra Motas, Sara Marcó, Albert Ribera, Víctor Sánchez, Xavier Sánchez, Joan Bertolin, Xavier León, Jennifer Pérez, Miguel Garcia, Pilar Villacampa, Jesús Ruberte, Anna Pujol, Virginia Haurigot, Fatima Bosch
Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it is not necessary to correct the genetic defect in all cells of an organ to achieve therapeutically significant levels of enzyme in body fluids, from which non-transduced cells can uptake the protein correcting their enzymatic deficiency. Animal models are instrumental in the development of new treatments for LSD. Here we report the generation of the first mouse model of the LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known as Sanfilippo syndrome type D...
February 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334528/why-prodrugs-and-propesticides-succeed
#3
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales with corresponding values of 20, 37 and 17% for proinsecticides, proherbicides and profungicides...
March 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28326039/estrone-sulfate-transport-and-steroid-sulfatase-activity-in-colorectal-cancer-implications-for-hormone-replacement-therapy
#4
Lorna C Gilligan, Ali Gondal, Vivien Tang, Maryam T Hussain, Anastasia Arvaniti, Anne-Marie Hewitt, Paul A Foster
Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28320104/sulfatase-2-promotes-the-growth-and-metastasis-of-colorectal-cancer-by-activating-akt-and-erk1-2-pathways
#5
Youmao Tao, Tao Han, Tao Zhang, Caixia Sun
The molecular mechanisms underlying the growth and metastasis of colorectal cancer (CRC) remain largely unknown. Sulfatase-2 (SULF2) was found to play critical roles in human cancers. Recent study reported that SULF1/2 overexpression resulted in increased viability and proliferation, and augmented cell migration in CRC cells. However, the expression of SULF2 and its underlying molecular mechanisms in CRC remain unknown. In this study, we found that the expressions of SULF2 in CRC tissues and cell lines were significantly increased compared to control groups...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28315670/sulfatase-activity-assay-using-an-activity-based-probe-by-generation-of-n-methyl-isoindole-under-reducing-conditions
#6
Hey Young Yoon, Jong-In Hong
Sulfatases catalyze the hydrolysis of sulfate esters that are present in a range of biomolecules. This is an important step in several biological processes such as cellular degradation, hormone regulation, and cell signaling. We have developed a new activity-based sulfatase probe (probe 1) that generates a fluorescent N-methylisoindole upon hydrolysis by sulfatase. Because of the autoxidation of N-methylisoindole, the sulfatase activity was also tested under reducing conditions, containing either glutathione (GSH) or tris(2-carboxyethyl)phosphine (TCEP), exhibiting little change in kinetic parameters compared to non-reducing conditions...
March 16, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28302098/in-vivo-confocal-microscopy-of-pre-descemet-corneal-dystrophy-associated-with-x-linked-ichthyosis-a-case-report
#7
Hui Shi, Xiao-Feng Qi, Tao-Tao Liu, Qian Hao, Xiao-Hong Li, Ling-Ling Liang, Yi-Miao Wang, Zhi-Hua Cui
BACKGROUND: Pre-Descemet corneal dystrophy (PDCD) is characterized by the presence of numerous, tiny, polymorphic opacities immediately anterior to Descemet membrane, which is a rare form of corneal stromal dystrophy and hard to be diagnosed. In vivo confocal microscopy (IVCM) is a useful tool to examine the minimal lesions of the cornea at the cellular level. In this article, we report a rare case of PDCD associated with X-linked ichthyosis and evaluate IVCM findings. CASE PRESENTATION: We present a 34-year-old male Chinese patient with PDCD associated with X-linked ichthyosis...
March 16, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28293481/a-genetic-variant-within-sts-previously-associated-with-inattention-in-boys-with-attention-deficit-hyperactivity-disorder-is-associated-with-enhanced-cognition-in-healthy-adult-males
#8
Trevor Humby, Amelia Fisher, Christopher Allen, Meghann Reynolds, Annette Hartman, Ina Giegling, Dan Rujescu, William Davies
INTRODUCTION: The enzyme steroid sulfatase (STS) converts sulfated steroids to their non-sulfated forms. Deficiency for this enzyme is associated with inattention but preserved response control. The polymorphism rs17268988 within the X-linked STS gene is associated with inattentive, but not other, symptoms in boys with attention deficit hyperactivity disorder (ADHD). METHODS: We initially tested whether rs17268988 genotype was associated with attention, response control, and underlying aspects of cognition, using questionnaires and neuropsychological tasks, in two independent cohorts of healthy adult males...
March 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28284963/a-structural-appraisal-of-sterol-carrier-protein-2
#9
REVIEW
Noelia I Burgardt, Alejo R Gianotti, Raúl G Ferreyra, Mario R Ermácora
Sterol Carrier Protein 2 (SCP2) has been associated with lipid binding and transfer activities. However, genomic, proteomic, and structural studies revealed that it is an ubiquitous domain of complex proteins with a variety functions in all forms of life. High-resolution structures of representative SCP2 domains are available, encouraging a comprehensive review of the structural basis for its success. Most SCP2 domains pertain to three major families and are frequently found as stand-alone or at the C-termini of lipid related peroxisomal enzymes, acetyltransferases causing bacterial resistance, and bacterial environmentally important sulfatases...
March 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28274582/estrogen-receptor-agonists-antagonists-in-breast-cancer-therapy-a-critical-review
#10
REVIEW
A Jameera Begam, S Jubie, M J Nanjan
Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer...
February 23, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28273623/changes-in-enzymatic-activities-in-metal-contaminated-and-reclaimed-lands-in-northern-ontario-canada
#11
Ramya Narendrula-Kotha, Kabwe K Nkongolo
Metal and sulfur dioxide (SO2) contaminations in Northern Ontario (Canada), especially in the Greater Sudbury Region (GSR) caused by mining activities have resulted in severe environmental degradations. A long term restoration program has led to significant landscape changes and healthy ecosystems. The objective of this study was to assess variation in enzymatic activities and soil respiration in metal contaminated and reclaimed ecosystems. Soil analysis revealed that respiration rates were higher in metal contaminated limed soils (65ppm) compared to adjacent unlimed areas (35ppm)...
March 5, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28257906/comparative-and-evolutionary-studies-of-mammalian-arylsulfatase-and-sterylsulfatase-genes-and-proteins-encoded-on-the-x-chromosome
#12
Roger S Holmes
At least 19 sulfatase genes have been reported on the human genome, including four arylsulfatase (ARS) genes (ARSD; ARSE; ARSF; ARSH) and a sterylsulfatase (STS) gene located together on the X-chromosome. Bioinformatic analyses of mammalian genomes were undertaken using known human STS and ARS amino acid sequences to study the evolution of these genes and proteins encoded on eutherian and marsupial genomes. Several domain regions and key residues were conserved including signal peptides, active site residues, metal (Ca(2+)) and substrate binding sequences, transmembranes and N-glycosylation sites...
February 24, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28210640/muscle-weakness-a-misleading-presentation-in-children-with-distinctive-syndromic-entities-clinical-case-reports
#13
Ali Al Kaissi, Sergey Ryabykh, Polina Ochirova, Vladimir Kenis, Jochen G Hofstätter, Franz Grill, Rudolf Ganger, Susanne Gerit Kircher
Marked ligamentous hyperlaxity and muscle weakness/wasting associated with awkward gait are the main deficits confused with the diagnosis of myopathy. Seven children (6 boys and 1 girl with an average age of 8 years) were referred to our department because of diverse forms of skeletal abnormalities. No definitive diagnosis was made, and all underwent a series of sophisticated investigations in other institutes in favor of myopathy. We applied our methodology through the clinical and radiographic phenotypes followed by targeted genotypic confirmation...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28207863/identification-of-age-dependent-motor-and-neuropsychological-behavioural-abnormalities-in-a-mouse-model-of-mucopolysaccharidosis-type-ii
#14
Hélène F E Gleitz, Claire O'Leary, Rebecca J Holley, Brian W Bigger
Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this...
2017: PloS One
https://www.readbyqxmd.com/read/28193024/evaluating-tumor-associated-activity-of-extracellular-sulfatase-by-analyzing-naturally-occurring-substrate-in-tumor-microenvironment-of-hepatocellular-carcinoma
#15
Yue Yu, Hao Li, Yucai Yang, Yitao Ding, Zhaoxia Wang, Genxi Li
The progress of cancer is intimately connected with the activity of the extracellular matrix (ECM) enzymes. To evaluate the promoting effect of these enzymes on tumor development in a pathological biocontext, we propose in this work to analyze their natural substrates in the ECM. This strategy is demonstrated by studying heparan sulfate (HS), the substrate of ECM sulfatase, in the development of hepatocellular carcinoma (HCC). An assay is designed to study the abundance and sulfation of HS and to evaluate the interactions between HS and the growth factors, such as fibroblast growth factor 2 (FGF2)...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28186595/-analysis-of-ids-gene-mutation-in-a-family-affected-with-mucopolysaccharidosis-type%C3%A2
#16
Yiying Li, Shiyue Mei, Xiangdong Kong, Zhenhua Zhao, Xiaofan Zhu, Xinyu Yang, Zhi Qin, Han Wu
OBJECTIVE: To detect potential mutation of iduronate-2-sulfatase (IDS) gene in a family affected with mucopolysaccharidosis type Ⅱ (MPS Ⅱ). METHODS: For the proband and his unaffected mother, the whole coding sequence of the IDS gene was analyzed with PCR and bidirectional Sanger sequencing. RESULTS: A novel splicing mutation, c.709-1G>A, was detected in the proband, for which his mother was heterozygous. CONCLUSION: The c...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28181906/activity-of-urine-arylsulfatase-a-in-brain%C3%A2-dead-graft-donors-is-a-predictor-of-early-and-late-graft-function
#17
Ewa Kwiatkowska, Leszek Domanski, Joanna Bober, Krzysztof Safranow, Andrzej Pawlik, Kazimierz Ciechanowski
OBJECTIVE: Human lysosomal arylsulfatase A (ASA) is a member of the sulfatase family. Arylsulfatase A is required to degrade sulfatides. Sulfatides occur in the myelin sheets of the central and peripheral nervous system. In this study we evaluated the urine activity of lysosomal enzyme arylsulfatase A in brain‑dead donors as a marker and predictor of short - and long‑term renal allograft function. PATIENTS/METHODS: We analyzed data from kidney recipients who received organs from brain‑dead donors...
January 4, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28170435/preventive-effect-of-dietary-astaxanthin-on-uva-induced-skin-photoaging-in-hairless-mice
#18
Toshiyuki Komatsu, Suguru Sasaki, Yuki Manabe, Takashi Hirata, Tatsuya Sugawara
Astaxanthin, a carotenoid found mainly in seafood, has potential clinical applications due to its antioxidant activity. In this study, we evaluated the effect of dietary astaxanthin derived from Haematococcus pluvialis on skin photoaging in UVA-irradiated hairless mice by assessing various parameters of photoaging. After chronic ultraviolet A (UVA) exposure, a significant increase in transepidermal water loss (TEWL) and wrinkle formation in the dorsal skin caused by UVA was observed, and dietary astaxanthin significantly suppressed these photoaging features...
2017: PloS One
https://www.readbyqxmd.com/read/28153673/quantitative-analysis-of-menthol-in-human-urine-using-solid-phase-microextraction-and-stable-isotope-dilution-gas-chromatography-mass-spectrometry
#19
Wenlin Huang, Benjamin C Blount, Clifford H Watson, Christina Watson, David M Chambers
To accurately measure menthol levels in human urine, we developed a method using gas chromatography/electron ionization mass spectrometry with menthol-d4 stable isotope internal standardization. We used solid phase microextraction (SPME) headspace sampling for collection, preconcentration and automation. Conjugated forms of menthol were released using β-glucuronidase/sulfatase to allow for measuring total menthol. Additionally, we processed the specimens without using β-glucuronidase/sulfatase to quantify the levels of unconjugated (free) menthol in urine...
February 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28152429/synthesis-and-biological-evaluation-of-fluorinated-n-benzoyl-and-n-phenylacetoyl-derivatives-of-3-4-aminophenyl-coumarin-7-o-sulfamate-as-steroid-sulfatase-inhibitors
#20
Mateusz Daśko, Maja Przybyłowska, Janusz Rachon, Maciej Masłyk, Konrad Kubiński, Majus Misiak, Andrzej Składanowski, Sebastian Demkowicz
In the present work, we report convenient methods for the synthesis of 3-(4-aminophenyl)-coumarin-7-O-sulfamate derivatives N-acylated with fluorinated analogues of benzoic or phenylacetic acid as steroid sulfatase (STS) inhibitors. The design of these potential STS inhibitors was supported by molecular modeling techniques. Additionally, computational docking methods were used to determine the binding modes of the synthesized inhibitors and to identify potential interactions between inhibitors and amino acid residues located in the active site of STS...
January 22, 2017: European Journal of Medicinal Chemistry
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