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Lysosomal Hydrolases (lysosomal + hydrolase)
Selected AbstractsIdentification of four novel mutations in five unrelated Korean families with Fabry diseaseCLINICAL GENETICS, Issue 3 2000J-K Lee Fabry disease is a X-linked recessively inherited metabolic disorder, which results from the deficient activity of the lysosomal hydrolase ,-galactosidase A leading to the systemic deposition of glycosphingolipids with terminal ,-galactosyl moieties. Single-strand conformation polymorphism (SSCP) analysis was performed, followed by DNA sequencing of PCR amplified exons of the human ,-galactosidase A gene in 5 unrelated Korean patients with classic Fabry disease. Five different mutations were identified; two nonsense mutations (Y86X and R342X), one missense mutation (D266N), and two small deletions (296del2 and 802del4). Except for R342X mutation, four were novel mutations (Y86X, D266N, 296del2, 802del4). A T to G transversion at nucleotide position 5157 in exon 2 caused a tyrosine-to-stop substitution at codon 86. A G to A transition at position 10 287 in exon 5 substituted an asparagine for an aspartate at codon 266. Mutation 296del2 in exon 2 resulted in a frame shift with a stop signal at the 22th codon downstream from the mutation, whereas mutation 802del4 resulted in a stop codon at the site of 4 bp deletion. In addition, the 802del4 was found to be a de novo mutation. This is the first report on mutation analysis of the human ,-galactosidase A gene in Korean patients with Fabry disease. [source] MBSJ MCC Young Scientist Award 2009 REVIEW: Selective autophagy regulates various cellular functionsGENES TO CELLS, Issue 9 2010Masaaki Komatsu Autophagy is a self-eating system conserved among eukaryotes, in which cellular components including organelles are entrapped into a double membrane structure called the autophagosome and then degraded by lysosomal hydrolases. In addition to its role in supplying amino acids in response to nutrient starvation, autophagy is involved in quality control to maintain cell health. Thus, inactivation of autophagy causes the formation of cytoplasmic protein inclusions, which comprise misfolded proteins and the accumulation of many degenerated organelles, resulting in liver injury, diabetes, myopathy and neurodegeneration. Furthermore, although autophagy has been considered nonselective, increasing evidence points to the selectivity of autophagy in sorting vacuolar enzymes and removal of aggregate-prone proteins and unwanted organelles. Such selectivity allows diverse cellular regulation, similar to the ubiquitin proteasome pathway. In this review, we discuss the physiological roles of selective autophagy and their molecular mechanisms. [source] Mechanism of protective action of mangiferin on suppression of inflammatory response and lysosomal instability in rat model of myocardial infarctionPHYTOTHERAPY RESEARCH, Issue 6 2009S. Prabhu Abstract Lysosomal instability has been suggested as a major factor in the development of cellular injury during myocardial necrosis through the formation of inflammatory mediators. The present study was designed to investigate the effect of mangiferin on lysosomal hydrolases and TNF- , production during isoproterenol (ISPH) induced myocardial necrosis in rats. The rats given ISPH (200 mg/kg body weight twice, subcutaneous) for 2 days showed a significant increase in plasma TNF- , production, serum and heart lysosomal hydrolases activity. ISPH administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin-D and , -glucuronidase in mitochondrial, nuclear, lysosomal and microsomal fractions. Pretreatment with mangiferin (100 mg/kg body weight, intraperitoneally) for 28 days, significantly prevented the alterations and restored the enzyme activities to near-normal status. These findings demonstrate that mangiferin could preserve lysosomal integrity through decrease in the inflammatory process and hence establish the cardioprotective effect of mangiferin. Copyright © 2009 John Wiley & Sons, Ltd. [source] Exclusion of NEU1 and PPGB from candidate genes for a lysosomal storage disease in Japanese Black cattleANIMAL SCIENCE JOURNAL, Issue 5 2009Ali Akbar MASOUDI ABSTRACT A case of lysosomal storage disease has been reported in a calf of Japanese Black cattle. Lysosomal storage diseases are hereditary diseases caused by deficiency of lysosomal hydrolases. The clinical and pathological features and accumulated substrates of the affected animal indicated a possibility of sialidosis or galactosialidosis caused by deficiency of neuraminidase (NEU1) or protective protein for ,-galactosidase (PPGB). In the present study, we investigated nucleotide sequences of the genes encoding these two proteins to evaluate whether mutation of these genes is involved in this disease. We determined cattle genomic sequences of these two genes by using bovine EST sequences and the nucleotide sequences of all exons of these genes were compared between affected and normal animals. The results showed several nucleotide substitutions, but none of them was a functional mutation or specific to the affected animal. Furthermore, genotyping of the microsatellite markers in the vicinity of these two genes revealed no homozygosity of the chromosomal regions including these genes in the affected animal. These findings indicated that neither NEU1 nor PPGB gene is responsible for the lysosomal storage disease of Japanese Black cattle and therefore the disease is neither sialidosis nor galactosialidosis. [source] Calcium sensing and cell signaling processes in the local regulation of osteoclastic bone resorptionBIOLOGICAL REVIEWS, Issue 1 2004Mone Zaidi ABSTRACT The skeletal matrix in terrestrial vertebrates undergoes continual cycles of removal and replacement in the processes of bone growth, repair and remodeling. The osteoclast is uniquely important in bone resorption and thus is implicated in the pathogenesis of clinically important bone and joint diseases. Activated osteoclasts form a resorptive hemivacuole with the bone surface into which they release both acid and osteoclastic lysosomal hydrolases. This article reviews cell physiological studies of the local mechanisms that regulate the resorptive process. These used in vitro methods for the isolation, culture and direct study of the properties of neonatal rat osteoclasts. They demonstrated that both local microvascular agents and products of the bone resorptive process such as ambient Ca2+ could complement longer-range systemic regulatory mechanisms such as those that might be exerted through calcitonin (CT). Thus elevated extracellular [Ca2+], or applications of surrogate divalent cation agonists for Ca2+, inhibited bone resorptive activity and produced parallel increases in cytosolic [Ca2+], cell retraction and longer-term inhibition of enzyme release in isolated rat osteoclasts. These changes showed specificity, inactivation, and voltage-dependent properties that implicated a cell surface Ca2+ receptor (CaR) sensitive to millimolar extracellular [Ca2+]. Pharmacological, biophysical and immunochemical evidence implicated a ryanodine-receptor (RyR) type II isoform in this process and localized it to a unique, surface membrane site, with an outward-facing channel-forming domain. Such a surface RyR might function either directly or indirectly in the process of extracellular [Ca2+] sensing and in turn be modulated by cyclic adenosine diphosphate ribose (cADPr) produced by the ADP-ribosyl cyclase, CD38. The review finishes by speculating about possible detailed models for these transduction events and their possible interactions with other systemic mechanisms involved in Ca2+ homeostasis as well as the possible role of the RyR-based signaling mechanisms in longer-term cell regulatory processes. [source] Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III , identification of eight novel mutationsCLINICAL GENETICS, Issue 1 2009M Encarnação Mucolipidosis II (ML II) and mucolipidosis III (ML III) are diseases in which the activity of the uridine diphosphate (UDP)- N -acetylglucosamine:lysosomal enzyme N -acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is absent or reduced, respectively. In the absence of mannose phosphorylation, trafficking of lysosomal hydrolases to the lysosome is impaired. In these diseases, mistargeted lysosomal hydrolases are secreted into the blood, resulting in lysosomal deficiency of many hydrolases and a storage-disease phenotype. GlcNAc-phosphotransferase is a multimeric transmembrane enzyme composed of three subunits (,, , and ,) encoded by two genes ,GNPTAB and GNPTG. Defects in GNPTAB result in ML II and III whereas mutations in GNPTG were only found in ML III patients. We have performed a molecular analysis of the GNPTAB and GNPTG genes in 13 mucolipidosis II and III patients (10 Portuguese, one Finnish, one Spanish of Arab origin and one Indian). Mutations were identified by the study of both cDNA and gDNA. The GNPTAB and GNPTG mRNA expressions were determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The study led to the identification of 11 different mutations. Eight of these mutations are novel, six in the GNPTAB gene [c.121delG (V41FfsX42), c.440delC (A147AfsX5), c.2249_50insA (N750KfsX8), c.242G>T (W81L), c.1208T>C (I403T) and c.1999G>T (p.E667X)] and two in the GNPTG gene [c.610-1G>T and c.639delT (F213LfsX7)]. With regard to the mRNA expression studies, the values obtained by qRT-PCR indicate the possible existence of feedback regulation mechanisms between ,/, and the , subunits. [source] | ||||||||||