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Lysosomal acid lipase

Hanrui Zhang
PURPOSE OF REVIEW: Lysosomal acid lipase (LAL), encoded by the LIPA gene, is an essential lysosomal enzyme that hydrolyzes cholesteryl ester and triglyceride delivered to the lysosome. This review highlights the novel pathophysiological role of LAL, the functional genomic discoveries of LIPA as a risk locus for coronary heart diseases (CHD), and the clinical advance in therapies for LAL deficiency. RECENT FINDINGS: The essential role of LAL in lipid metabolism has been confirmed in human and mice with LAL deficiency...
March 15, 2018: Current Opinion in Lipidology
Elmar Aigner, Alexandra Feldman, Daniel Neureiter, Christian Datz, Vlad Ratziu, Bernhard Paulweber
No abstract text is available yet for this article.
March 2018: American Journal of Gastroenterology
Marco Antonio Curiati, Sandra Obikawa Kyosen, Vanessa Gonçalves Pereira, Francy Reis da Silva Patrício, Ana Maria Martins
Lysosomal acid lipase (LAL) deficiency is an autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene that leads to premature organ damage and mortality. We present retrospective data from medical records of 5 Brazilian patients, showing the broad clinical spectrum of the disease.
2018: Case Reports in Pediatrics
Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, François Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea E Bochem, Kees G Hovingh, Edward B Thorp, Emmanuel L Gautier, Dagmar Kratky, Paul A Da Silva-Jardine, Laurent Yvan-Charvet
<u>Rationale:</u> Macrophages face a substantial amount of cholesterol following the ingestion of apoptotic cells and the lysosomal acid lipase (LIPA) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment. <u>Objective:</u> Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo. <u>Methods and Results:</u> We show that LIPA inhibition causes a defective efferocytic response due to impaired generation of 25-OHC and 27-OHC...
March 9, 2018: Circulation Research
Ze-Cheng Jin, Toshihiko Kitajima, Weijie Dong, Yi-Fan Huang, Wei-Wei Ren, Feng Guan, Yasunori Chiba, Xiao-Dong Gao, Morihisa Fujita
Recombinant therapeutic proteins are becoming very important pharmaceutical agents for treating intractable diseases. Most biopharmaceutical proteins are produced in mammalian cells because this ensures correct folding and glycosylation for protein stability and function. However, protein production in mammalian cells has several drawbacks, including heterogeneity of glycans attached to the produced protein. In this study, we established cell lines with high-mannose-type asparagine (N)-linked, low-complexity glycans...
February 23, 2018: Journal of Biological Chemistry
Malgorzata Lysek-Gladysinska, Anna Wieczorek, Anna Walaszczyk, Karol Jelonek, Artur Jozwik, Monika Pietrowska, Wolfgang Dörr, Dorota Gabrys, Piotr Widlak
The aim of the study was to investigate long-term effects of radiation on the (ultra)structure and function of the liver in mice. The experiments were conducted on wild-type C57BL/6J and apolipoprotein E knock-out (ApoE-/- ) male mice which received a single dose (2 or 8 Gy) of X-rays to the heart with simultaneous exposure of liver to low doses (no more than 30 and 120 mGy, respectively). Livers were collected for analysis 60 weeks after irradiation and used for morphological, ultrastructural, and biochemical studies...
February 22, 2018: Radiation and Environmental Biophysics
Laura López de Frutos, Jorge J Cebolla, Pilar Irún, Ralf Köhler, Pilar Giraldo
BACKGROUND: Erythrocyte volume regulation and membrane elasticity are essential for adaptation to osmotic and mechanical stress, and life span. Here, we evaluated whether defective cholesterol trafficking caused by the rare lysosomal storages diseases (LSDs), Niemann-Pick type C (NPC) and Lysosomal acid lipase (LAL) deficiency (LALD) impairs these properties. Moreover, we tested whether measurements of cholesterol membrane content and osmotic resistance serve as a screening test for these LSDs...
February 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Julian F Guest, Andy Ingram, Nadia Ayoub, Christian J Hendriksz, Elaine Murphy, Yusof Rahman, Patrick McKiernan, Helen Mundy, Patrick Deegan
OBJECTIVE: To estimate clinical progression and resource utilisation together with the associated costs of managing children and adults with LAL Deficiency, at a tertiary referral centre in the UK. METHODS: A retrospective chart review was undertaken of patients in the UK with a confirmed diagnosis of LAL Deficiency who were managed at a LAL Deficiency tertiary referral treatment centre. Patients' pathways, treatment patterns, health outcomes and resource use were quantified over differing lengths of time for each patient enabling the NHS cost of patient management in tertiary care to be estimated...
2018: PloS One
Madalina Duta-Mare, Vinay Sachdev, Christina Leopold, Dagmar Kolb, Nemanja Vujic, Melanie Korbelius, Dina C Hofer, Wenmin Xia, Katharina Huber, Martina Auer, Benjamin Gottschalk, Christoph Magnes, Wolfgang F Graier, Andreas Prokesch, Branislav Radovic, Juliane G Bogner-Strauss, Dagmar Kratky
Lysosomal acid lipase (LAL) is the only known enzyme, which hydrolyzes cholesteryl esters and triacylglycerols in lysosomes of multiple cells and tissues. Here, we explored the role of LAL in brown adipose tissue (BAT). LAL-deficient (Lal-/-) mice exhibit markedly reduced UCP1 expression in BAT, modified BAT morphology with accumulation of lysosomes, and mitochondrial dysfunction, consequently leading to regular hypothermic events in mice kept at room temperature. Cold exposure resulted in reduced lipid uptake into BAT, thereby aggravating dyslipidemia and causing life threatening hypothermia in Lal-/- mice...
January 24, 2018: Biochimica et Biophysica Acta
Maja Di Rocco, Livia Pisciotta, Annalisa Madeo, Marta Bertamino, Stefano Bertolini
BACKGROUND: Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its consequence, plasmatic concentration of low density lipoproteins and other apoB-containing lipoproteins, that are the substrate of lysosomal acid lipase, are decreased...
January 27, 2018: Orphanet Journal of Rare Diseases
Madalina Duta-Mare, Vinay Sachdev, Nemanja Vujic, Katharina Huber, Wenmin Xia, Melanie Korbelius, Dagmar Kratky
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Ekaterina Zakharova, Elena Kamenets, Galina Baydakova, Svetlana Mikhaylova, Tatiana Strokova, Madlena Bagaeva, Alla Lavrova, Maria Amelina, Natalia Pichkur
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Eric Bruckert, Sachin Marulkar, Mark Friedman, Don Wilson
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Euridiki Drogari, George Pappas, Eleftherios Iliadis, Nina Manolaki
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Enrique Rodríguez-García, Miriam Gil-Serret, María Concepción García-Jiménez, María Luisa González-Diéguez, Pablo Del Valle Loarte, Miguel Angel Barba-Romero, David Gil-Ortega, Rosa Bernal-López, Nuria Amigó, Raquel Yahyaoui
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Timothy M Reynolds, Clare Mewies, John Hamilton, Anthony S Wierzbicki
AIMS: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder of cholesterol ester storage associated with hepatic disease, cirrhosis and accelerated atherosclerosis. Its prevalence in the general population, patients with dyslipidaemia and raised transaminases is unclear. This study attempted to identify the prevalence of LALD from patients with abnormal results in laboratory databases. METHODS: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of low high-density lipoprotein-cholesterol (≤0...
January 22, 2018: Journal of Clinical Pathology
David M Ng, Amanda J Hooper, Matthew I Bellgard, John R Burnett
PURPOSE OF REVIEW: We review the role, utility and current status of patient registries for rare genetic lipid disorders. RECENT FINDINGS: The creation and maintenance of rare genetic lipid disorder patient registries is critical for disease monitoring, improving clinical best practice, facilitating research and enabling the development of novel therapeutics. An open-source disease registry platform, termed the Rare Disease Registry Framework, has been developed, optimized and deployed for homozygous familial hypercholesterolemia...
January 17, 2018: Current Opinion in Lipidology
Sophia Masi, Naveen Chennamaneni, Frantisek Turecek, C Ronald Scott, Michael H Gelb
BACKGROUND: Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and cholesterol ester storage disease. With the recent introduction of enzyme replacement therapy to manage LAL deficiency comes the need for a reliable assay of LAL enzymatic activity that can be applied to dried blood spots (DBS). METHODS: We prepared and tested a library of analogs of palmitoyl 4-methylumbelifferyl esters to find a highly active and specific substrate for LAL in DBS. The LAL assay was optimized leading to both LC-MS/MS and fluorometric assay of LAL...
January 16, 2018: Clinical Chemistry
Ornella Guardamagna, Federica Guaraldi
LAL-deficiency (LAL-D) is a rare and systemic condition, secondary to LIPA gene mutations, responsible for lysosomal accumulation of cholesteryl esters and triglycerides, whose manifestations are very heterogeneous in terms of age of onset, severity and type of clinical and radiological manifestations. Dyslipidemia, hepatomegaly and hepatosteatosis with increased levels of transaminases are the most common features. The increased risk of premature atherosclerosis and cardiovascular disorders,, secondary to a generalized alteration of lipid profile and lipoprotein dysfunction associated with LAL-D, has been increasingly pointed out...
January 11, 2018: Current Pediatric Reviews
Kwang Yeon Kim, Ju Whi Kim, Kyung Jae Lee, Eunhyang Park, Gyeong Hoon Kang, Young Hun Choi, Woo Sun Kim, Jung Min Ko, Jin Soo Moon, Jae Sung Ko
Patients with lysosomal acid lipase (LAL) deficiency and glycogen storage disease (GSD) demonstrated hepatomegaly and dyslipidemia. In our case, a 6-year-old boy presented with hepatosplenomegaly. At 3 years of age, GSD had been diagnosed by liver biopsy at another hospital. He showed elevated serum liver enzymes and dyslipidemia. Liver biopsy revealed diffuse microvesicular fatty changes in hepatocytes, septal fibrosis and foamy macrophages. Ultrastructural examination demonstrated numerous lysosomes that contained lipid material and intracytoplasmic cholesterol clefts...
December 2017: Pediatric Gastroenterology, Hepatology & Nutrition
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