کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833605 | 1065799 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reversal of advanced disease in lysosomal acid lipase deficient mice: A model for lysosomal acid lipase deficiency disease
ترجمه فارسی عنوان
معکوس شدن بیماری پیشرفته در موش های کمبود لیپاز لیزوزوم اسید: یک مدل برای بیماری کمبود لیپوزیس اسید لیزوزوم
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Lysosomal acid lipase (LAL) is an essential enzyme that hydrolyzes triglycerides (TG) and cholesteryl esters (CE) in lysosomes. Mutations of the LIPA gene lead to Wolman disease (WD) and cholesterol ester storage disease (CESD). The disease hallmarks include hepatosplenomegaly and extensive storage of CE and/or TG. The effects of intravenous investigational enzyme therapy (ET) on survival and efficacy were evaluated in Lipa knock out, lalâ/â mice with advanced disease using recombinant human LAL (rhLAL). Comparative ET was conducted with lower doses (weekly, 0.8 and 3.2Â mg/kg) beginning at 16Â weeks (study 1), and with higher dose (10Â mg/kg) in early (8-weeks), middle (16-weeks) and late (24-weeks) disease stages (study 2). In study 1, rhLAL extended the life span of lalâ/â mice in a dose dependent manner by 52 (0.8Â mg/kg) or 94 (3.2Â mg/kg) days. This was accompanied by partial correction of cholesterol and TG levels in spleen and liver. In study 2, the high dose resulted in a significant improvement in organ size (liver, spleen and small intestine) and tissue histology as well as significant decreases in cholesterol and TG in all three groups. In the treated livers and spleens the cholesterol and TG levels were reduced to below treatment initiation levels indicating a reversal of disease manifestations, even in advanced disease. ET diminished liver fibrosis and macrophage proliferation. These results show that LAL deficiency can be improved biochemically and histopathologically by various dosages of ET, even in advanced disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 112, Issue 3, July 2014, Pages 229-241
Journal: Molecular Genetics and Metabolism - Volume 112, Issue 3, July 2014, Pages 229-241
نویسندگان
Ying Sun, You-Hai Xu, Hong Du, Brian Quinn, Benjamin Liou, Lori Stanton, Venette Inskeep, Huimin Ran, Phillip Jakubowitz, Nicholas Grilliot, Gregory A. Grabowski,