88 results match your criteria fibroblasts iva


Umbilical mesenchymal stem cell-derived extracellular vesicles as enzyme delivery vehicle to treat Morquio A fibroblasts.

Stem Cell Res Ther 2021 May 6;12(1):276. Epub 2021 May 6.

Department of Pediatrics, School of Medicine, Saint Louis University, 1100 South Grand Blvd., Room 313, St. Louis, MO, 63104, USA.

Background: Mucopolysaccharidosis IVA (Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which results in the accumulation of the glycosaminoglycans (GAGs), keratan sulfate, and chondroitin-6-sulfate in the lysosomes of all tissues causing systemic dysfunction. Current treatments include enzyme replacement therapy (ERT) which can treat only certain aspects of the disease such as endurance-related biological endpoints. A key challenge in ERT is ineffective enzyme uptake in avascular tissues, which makes the treatment of the corneal, cartilage, and heart valvular tissue difficult. Read More

View Article and Full-Text PDF

Evaluation of HIV-1 derived lentiviral vectors as transductors of Mucopolysaccharidosis type IV a fibroblasts.

Gene 2021 May 23;780:145527. Epub 2021 Feb 23.

Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia. Electronic address:

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease produced by the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, leading to glycosaminoglycans (GAGs) accumulation. Since currently available treatments remain limited and unspecific, novel therapeutic approaches are essential for the disease treatment. In an attempt to reduce treatment limitations, gene therapy rises as a more effective and specific alternative. Read More

View Article and Full-Text PDF

Bromocriptine as a Novel Pharmacological Chaperone for Mucopolysaccharidosis IV A.

ACS Med Chem Lett 2020 Jul 24;11(7):1377-1385. Epub 2020 Jun 24.

Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C. 110231, Colombia.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the gene encoding for the enzyme -acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to lysosomal accumulation of keratan sulfate (KS) and chondroitin-6-sulfate. In this study, we identified and characterized bromocriptine (BC) as a novel PC for MPS IVA. BC was identified through virtual screening and predicted to be docked within the active cavity of GALNS in a similar conformation to that observed for KS. Read More

View Article and Full-Text PDF

Expression of genes involved in apoptosis is dysregulated in mucopolysaccharidoses as revealed by pilot transcriptomic analyses.

Cell Biol Int 2021 Mar 12;45(3):549-557. Epub 2020 Mar 12.

Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.

Mucopolysaccharidoses (MPS), a group of lysosomal storage diseases (LSD), are inherited disorders caused by mutations in genes coding for enzymes involved in the degradation of glycosaminoglycans (GAGs). Therefore, accumulated GAGs in lysosomes lead to severe symptoms in patients and significantly shortened life span. Although GAG accumulation in cells is the primary cellular defect in MPS, recent reports indicated that severe changes in cellular processes occur there as secondary or tertiary effects, which may contribute significantly to the disease pathomechanism. Read More

View Article and Full-Text PDF

Biodegradable polyethylene glycol hydrogels for sustained release and enhanced stability of rhGALNS enzyme.

Drug Deliv Transl Res 2020 10;10(5):1341-1352

Department of Biomedical Engineering, Saint Louis University, 3507 Lindell Blvd, St. Louis, MO, 63103, USA.

Mucopolysaccharidosis IVA (Morquio A disease) is a genetic disorder caused by deficiency of N-acetylgalactosamine-6-sulfate-sulfatase (GALNS), leading to accumulation of keratan sulfate and chondroitin-6-sulfate in lysosomes. Many patients become wheelchair-dependent as teens, and their life span is 20-30 years. Currently, enzyme replacement therapy (ERT) is the treatment of choice. Read More

View Article and Full-Text PDF
October 2020

The interaction of ceramide 1-phosphate with group IVA cytosolic phospholipase A coordinates acute wound healing and repair.

Sci Signal 2019 12 3;12(610). Epub 2019 Dec 3.

Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL 33620, USA.

The sphingolipid ceramide 1-phosphate (C1P) directly binds to and activates group IVA cytosolic phospholipase A (cPLAα) to stimulate the production of eicosanoids. Because eicosanoids are important in wound healing, we examined the repair of skin wounds in knockout (KO) mice lacking cPLAα and in knock-in (KI) mice in which endogenous cPLAα was replaced with a mutant form having an ablated C1P interaction site. Wound closure rate was not affected in the KO or KI mice, but wound maturation was enhanced in the KI mice compared to that in wild-type controls. Read More

View Article and Full-Text PDF
December 2019

Enzyme-Loaded Gel Core Nanostructured Lipid Carriers to Improve Treatment of Lysosomal Storage Diseases: Formulation and In Vitro Cellular Studies of Elosulfase Alfa-Loaded Systems.

Pharmaceutics 2019 Oct 11;11(10). Epub 2019 Oct 11.

Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy. Campus Vida, University of Santiago de Compostela, 15872 Santiago de Compostela, Spain.

Mucopolysaccharidosis IVA (Morquio A) is a rare inherited metabolic disease caused by deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS). Until now, treatments employed included hematopoietic stem cell transplantation and enzyme replacement therapy (ERT); the latter being the most commonly used to treat mucopolysaccharidoses, but with serious disadvantages due to rapid degradation and clearance. The purpose of this study was to develop and evaluate the potential of nanostructured lipid carriers (NLCs) by encapsulating elosulfase alfa and preserving its enzyme activity, leading to enhancement of its biological effect in chondrocyte cells. Read More

View Article and Full-Text PDF
October 2019

The Role of MicroRNA-21 in Venous Neointimal Hyperplasia: Implications for Targeting miR-21 for VNH Treatment.

Mol Ther 2019 09 3;27(9):1681-1693. Epub 2019 Jul 3.

Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. Electronic address:

The molecular mechanism of hemodialysis access arteriovenous fistula (AVF) failure due to venous neointimal hyperplasia (VNH) is not known. The role of microRNA-21 (miR-21) in VNH associated with AVF failure was investigated by performing in vivo and in vitro experiments. In situ hybridization results revealed that miR-21 expression increased and was associated with fibroblasts in failed AVFs from patients. Read More

View Article and Full-Text PDF
September 2019

Identification of Ezetimibe and Pranlukast as Pharmacological Chaperones for the Treatment of the Rare Disease Mucopolysaccharidosis Type IVA.

J Med Chem 2019 07 25;62(13):6175-6189. Epub 2019 Jun 25.

National Center for Advancing Translational Sciences , National Institutes of Health , Bethesda , Maryland 20892 , United States.

Mucopolysaccharidosis type IVA (MPS IVA) is a rare disease caused by mutations in the gene encoding the lysosomal enzyme -acetylgalactosamine-6-sulfate sulfatase (GALNS). We report here two GALNS pharmacological chaperones, ezetimibe and pranlukast, identified by molecular docking-based virtual screening. These compounds bound to the active cavity of GALNS and increased its thermal stability as well as the production of recombinant GALNS in bacteria, yeast, and HEK293 cells. Read More

View Article and Full-Text PDF

Determination of major components from Radix Achyranthes bidentate using ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry and an evaluation of their anti-osteoporosis effect in vitro.

J Sep Sci 2019 Jul 15;42(13):2214-2221. Epub 2019 May 15.

Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, P. R. China.

Ecdysterone and saponins are the most characteristic components of Radix Achyranthes bidentate, which acts on the human body to promote collagen synthesis and stimulates cell growth. However, the relationship between these components and the differentiation of MC3T3-E1 osteoblastic cells is unknown. We developed a rapid ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry method for direct determination of one ecdysterone and four saponins in crude and salt-processed Radix Achyranthes bidentate. Read More

View Article and Full-Text PDF

Generation of an induced pluripotent stem cell line (TRNDi005-A) from a Mucopolysaccharidosis Type IVA (MPS IVA) patient carrying compound heterozygous p.R61W and p.WT405del mutations in the GALNS gene.

Stem Cell Res 2019 04 15;36:101408. Epub 2019 Feb 15.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Mucopolysaccharidosis type IVA (MPS IVA) is a rare genetic disease caused by mutations in the GALNS gene and is inherited in an autosomal recessive manner. GALNS encodes N-acetylgalactosamine-6-sulfatase that breaks down certain complex carbohydrates known as glycosaminoglycans (GAGs). Deficiency in this enzyme causes accumulation of GAGs in lysosomes of body tissues. Read More

View Article and Full-Text PDF

Anti-Obesity Activities of Chikusetsusaponin IVa and L. Seeds.

Nutrients 2018 Sep 3;10(9). Epub 2018 Sep 3.

Herbal Medicine Research Division, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea.

Obesity, a condition where excess body fat accumulates to the extent, causes a negative effect on health. Previously, we reported the extract of L. (DLL-Ex) inhibited high-fat diet (HFD)-induced increases in body weight and body fat mass and ameliorated increases in body weight. Read More

View Article and Full-Text PDF
September 2018

Atlantic salmon endothelial cells from the heart were more susceptible than fibroblasts from the bulbus arteriosus to four RNA viruses but protected from two viruses by dsRNA pretreatment.

Fish Shellfish Immunol 2017 Nov 4;70:214-227. Epub 2017 Sep 4.

Department of Biology, University of Waterloo, Waterloo, ON, Canada. Electronic address:

Heart diseases caused by viruses are major causes of Atlantic salmon aquaculture loss. Two Atlantic salmon cardiovascular cell lines, an endothelial cell line (ASHe) from the heart and a fibroblast cell line (BAASf) from the bulbus arteriosus, were evaluated for their response to four fish viruses, CSV, IPNV, VHSV IVa and VHSV IVb, and the innate immune agonist, double-stranded RNA mimic poly IC. All four viruses caused cytopathic effects in ASHe and BAASf. Read More

View Article and Full-Text PDF
November 2017

Lactosylceramide-Induced Phosphorylation Signaling to Group IVA Phospholipase A via Reactive Oxygen Species in Tumor Necrosis Factor-α-Treated Cells.

J Cell Biochem 2017 12 31;118(12):4370-4382. Epub 2017 May 31.

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.

The activity of α-type cytosolic phospholipase A (cPLA α, group IVA PLA ), which releases arachidonic acid (AA), is mainly regulated by the Ca -induced intracellular translocation/attachment of the enzyme to substrate membranes and its phosphorylation. We previously reported that tumor necrosis factor-α (TNFα) stimulated the formation of lactosylceramide (LacCer) in L929 fibroblast cells, and this lipid directly bound with and activated cPLA α [Nakamura et al. [2013] J. Read More

View Article and Full-Text PDF
December 2017

Cellular Assays for Evaluating Calcium-Dependent Translocation of cPLAα to Membrane.

Authors:
B Yun C C Leslie

Methods Enzymol 2017 20;583:71-99. Epub 2016 Oct 20.

National Jewish Health, Denver, CO, United States; University of Colorado Denver, Aurora, CO, United States. Electronic address:

The group IVA phospholipase A, commonly called cytosolic phospholipase Aα (cPLAα), is a widely expressed enzyme that hydrolyzes membrane phospholipid to produce arachidonic acid and lysophospholipids, which are precursors for a number of bioactive lipid mediators. Arachidonic acid is metabolized through the cyclooxygenase and lipoxygenase pathways for production of prostaglandins and leukotrienes that regulate normal physiological processes and contribute to disease pathogenesis. cPLAα is composed of an N-terminal C2 domain and a C-terminal catalytic domain that contains the Ser-Asp catalytic dyad. Read More

View Article and Full-Text PDF

Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia.

J Hum Genet 2017 Mar 1;62(3):355-360. Epub 2016 Dec 1.

Centro de Diagnóstico de Enfermedades Moleculares, Universidad Autónoma de Madrid, IdiPaz, CIBERER, ICIII, Madrid, Spain.

Isovaleric acidemia (IVA) is a rare disorder of leucine metabolism. We carried out a multicenter study of IVA patients diagnosed by newborn screening (NBS) or symptoms clinics over a period of 28 years in Spain. Evaluated at diagnosis, data included age, detection method, levels of C5 and IVG, enzymatic studies, clinical presentation parameters and genotype in 16 patients. Read More

View Article and Full-Text PDF

Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity.

Biochim Biophys Acta 2016 09 16;1861(9 Pt A):1083-1095. Epub 2016 Jun 16.

Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain. Electronic address:

Adipogenesis is the process of differentiation of immature mesenchymal stem cells into adipocytes. Elucidation of the mechanisms that regulate adipocyte differentiation is key for the development of novel therapies for the control of obesity and related comorbidities. Cytosolic group IVA phospholipase A2 (cPLA2α) is the pivotal enzyme in receptor-mediated arachidonic acid (AA) mobilization and attendant eicosanoid production. Read More

View Article and Full-Text PDF
September 2016

PIP4K2B: Coupling GTP Sensing to PtdIns5P Levels to Regulate Tumorigenesis.

Trends Biochem Sci 2016 06 28;41(6):473-475. Epub 2016 Apr 28.

The Inositide Laboratory, Centre for Biological Sciences, Highfield Campus, Southampton University, Southampton, SO17 1BJ, UK; INGM Istituto Nazionale Genetica Molecolare, Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Via Francesco Sforza, 35 - 20122 Milano, Italy, C.F. / P.IVA 04175700964. 3. Electronic address:

Although guanine nucleotides are essential for cell growth, how their levels are sensed in mammalian cells is unknown. Sumita et al. show that PIP4K2B, a phosphoinositide kinase, is a molecular sensor that transduces changes in GTP into changes in the levels of the phosphoinositide PtdIns5P to modulate tumour cell growth. Read More

View Article and Full-Text PDF

Cytosolic phospholipase A2α regulates G1 progression through modulating FOXO1 activity.

FASEB J 2016 Mar 7;30(3):1155-70. Epub 2015 Dec 7.

*Renal Division, Brigham and Women's Hospital, Department of Medicine, and Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA; Renal Division, Amiens Southern Hospital, Amiens, France; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; and Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

Group IVA phospholipase A2 [cytosolic phospholipase A2α (cPLA2α)] is a key mediator of inflammation and tumorigenesis. In this study, by using a combination of chemical inhibition and genetic approaches in zebrafish and murine cells, we identify a mechanism by which cPLA2α promotes cell proliferation. We identified 2 cpla2α genes in zebrafish, cpla2αa and cpla2αb, with conserved phospholipase activity. Read More

View Article and Full-Text PDF

Camphor Induces Proliferative and Anti-senescence Activities in Human Primary Dermal Fibroblasts and Inhibits UV-Induced Wrinkle Formation in Mouse Skin.

Phytother Res 2015 Dec 13;29(12):1917-25. Epub 2015 Oct 13.

Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju, Republic of Korea.

Camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one), a bicyclic monoterpene, is one of the major constituents of essential oils from various herbs such as rosemary, lavender, and sage. Read More

View Article and Full-Text PDF
December 2015

Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio-A syndrome-associated mutations.

Hum Mutat 2015 Mar;36(3):357-68

Molecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy.

Morquio A syndrome (MPS IVA) is a systemic lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), encoded by the GALNS gene. We studied 37 MPS IV A patients and defined genotype-phenotype correlations based on clinical data, biochemical assays, molecular analyses, and in silico structural analyses of associated mutations. We found that standard sequencing procedures, albeit identifying 14 novel small GALNS genetic lesions, failed to characterize the second disease-causing mutation in the 16% of the patients' cohort. Read More

View Article and Full-Text PDF

Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes.

PLoS One 2013 12;8(12):e83555. Epub 2013 Dec 12.

Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway.

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease of the joint characterized by chronic synovitis causing pain, swelling and loss of function due to destruction of cartilage and bone. The complex series of pathological events occurring in RA is largely regulated via excessive production of pro-inflammatory cytokines, the most prominent being tumor necrosis factor (TNF). The objective of this work was to elucidate possible involvement of group IVA cytosolic phospholipase A2 (cPLA2α) in TNF-induced regulation of synovitis and joint destructive effectors in RA, to evaluate the potential of cPLA2α as a future therapeutic target. Read More

View Article and Full-Text PDF
September 2014

Niemann-pick type C2 deficiency in human fibroblasts confers robust and selective activation of prostaglandin E2 biosynthesis.

J Biol Chem 2013 Aug 27;288(33):23696-703. Epub 2013 Jun 27.

Division of Rheumatology, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.

Activated fibroblasts, also known as myofibroblasts, are mediators of several major human pathologies including proliferative fibrotic disorders, invasive tumor growth, rheumatoid arthritis, and atherosclerosis. We previously identified Niemann-Pick type C2 (NPC2) protein as a negative regulator of fibroblast activation (Csepeggi, C., Jiang, M. Read More

View Article and Full-Text PDF

Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA.

Mol Genet Metab 2013 Sep-Oct;110(1-2):54-64. Epub 2013 Apr 10.

University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, UK.

Mucopolysaccharidosis type IVA (MPS IVA) was described in 1929 by Luis Morquio from Uruguay and James Brailsford from England, and was later found as an autosomal recessive lysosomal storage disease. MPS IVA is caused by mutations in the gene encoding the enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Reduced GALNS activity results in impaired catabolism of two glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS). Read More

View Article and Full-Text PDF

Spondyloepiphyseal dysplasias and bilateral legg-calvé-perthes disease: diagnostic considerations for mucopolysaccharidoses.

JIMD Rep 2013 9;11:125-32. Epub 2013 May 9.

Department of Medical Genetics, Children's Hospitals and Clinics of Minnesota, 2525 Chicago Avenue S., CSC 560, Minneapolis, MN, 55404, USA,

Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome, MIM 253200 ) is an autosomal recessive lysosomal storage disease (LSD) caused by decreased activity of arylsulfatase B (N-acetylgalactosamine 4-sulfatase) enzyme resulting in dermatan sulfate accumulation; mucopolysaccharidosis type IVA (MPS IVA, Morquio syndrome A, MIM 253000 ) by decreased activity of N-acetylgalactosamine 6-sulfatase enzyme resulting in accumulation of keratan sulfate. Clinical symptoms include coarse facial features, joint stiffness, hepatosplenomegaly, hip osteonecrosis, and dysostosis multiplex. MPS IVA symptoms are similar but with joint hypermobility. Read More

View Article and Full-Text PDF

Five novel mutations of GALNS in Korean patients with mucopolysaccharidosis IVA.

Am J Med Genet A 2013 Mar 8;161A(3):509-17. Epub 2013 Feb 8.

Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Mucopolysaccharidosis IVA (MPS IVA; OMIM #253000) is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme involved in the catabolism of keratan and chondroitin sulfate. In this study, we examined biochemical and genetic data from 6 Korean patients presenting with classic MPS IVA by measuring GALNS activity in peripheral blood leukocytes and skin fibroblasts. We initially identified Korean patients with MPS IVA by clinical, biochemical, and genetic analyses. Read More

View Article and Full-Text PDF

Diagnosing mucopolysaccharidosis IVA.

J Inherit Metab Dis 2013 Mar 1;36(2):293-307. Epub 2013 Feb 1.

Biochemical Genetics Laboratory, Greenwood Genetic Center, 106 Gregor Mendel Circle, Greenwood, SC 29646, USA.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc. Read More

View Article and Full-Text PDF

Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring.

Vet Microbiol 2012 Dec 20;161(1-2):66-76. Epub 2012 Jul 20.

Herring Conservation & Research Society, Nanaimo, BC V9T 6M4, Canada.

Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. Read More

View Article and Full-Text PDF
December 2012

The ω3-polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells.

Br J Pharmacol 2012 Dec;167(8):1691-701

Institut für Pharmakologie, Universität Bern, Bern, Switzerland.

Background And Purpose: ω3-polyunsaturated fatty acids (ω3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized.

Experimental Approach: Here we report on two new cPLA(2) inhibitors, the ω3-derivatives AVX001 and AVX002, and their effects on inflammatory PGE(2) production in cultures of renal mesangial cells.

Key Results: AVX001 and AVX002 dose-dependently inhibited the group IVA cytosolic phospholipase A(2) (cPLA(2) ) in an in vitro activity assay with similar IC(50) values for AVX001 and AVX002, whereas the known cPLA(2) inhibitor AACOCF(3) was less potent and docosahexaenoic acid (DHA) was inactive. Read More

View Article and Full-Text PDF
December 2012

Unfolded protein response is not activated in the mucopolysaccharidoses but protein disulfide isomerase 5 is deregulated.

J Inherit Metab Dis 2012 May 15;35(3):479-93. Epub 2011 Oct 15.

Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases (LSDs) caused by defects in lysosomal enzymes involved in the catabolism of glycosaminoglycans. The pathogenesis of these disorders is still not completely known, although inflammation and oxidative stress appear to be common mechanisms, as in all LSDs. Recently, it was hypothesized that endoplasmic reticulum (ER) stress followed by an unfolded protein response (UPR) could be another common pathogenetic mechanism in LSDs. Read More

View Article and Full-Text PDF