کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11987969 | 1051594 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Loss of Leucyl-tRNA synthetase b leads to ILFS1-like symptoms in zebrafish
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کلمات کلیدی
hpfmTORC1LARSaaRSsWISH - آرزو کردنAminoacyl-tRNA synthetases - آمینواسیل tRNA synthetaseshours post fertilization - ساعت پس از لقاحleucyl-tRNA synthetase - سنتتاز تیروزین لوسیلwild-type - نوع وحشیmechanistic target of rapamycin complex 1 - هدف مکانیکی مجتمع رپامایسین 1Liver - کبدWhole mount in situ hybridization - کل کوهنوردی در محلZebrafish - گورخرماهی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Leucyl-tRNA synthetase (LARS) is a kind of aminoacyl-tRNA synthetases (aaRSs), which is important for protein synthesis. Following the discovery of three clinical cases which carry LARS mutations, it has been designated as the infantile liver failure syndrome type 1 (ILFS1) gene. ILFS1 is a kind of infantile hepatopathy, which is difficult to diagnose and manage. As the mechanism underlying this disease is poorly understood and LARS is conserved among vertebrates, we obtained zebrafish larsbcq68 mutant via CRISPR/Cas9 technology to investigate the role of larsb in vivo. In mutant, the proliferation ability of liver was drastically decreased at later stages accompanied with severe DNA damage. Further studies demonstrated that the mTORC1 signaling was hyperactivated in larsbcq68 mutant. Inhibition of mTORC1 signaling pathway by Rapamycin or mTORC1 morpholino can partially rescue the liver failure of the mutants. These data revealed that larsb mutation caused ILFS1-like phenotype in zebrafish, and indicated this mutant may serve as a potential model for ILFS1. Furthermore, we demonstrated that rapamycin treatment can partially rescue the liver defect in mutants, thus providing a practicable therapeutic plan for ILFS1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 505, Issue 2, 28 October 2018, Pages 378-384
Journal: Biochemical and Biophysical Research Communications - Volume 505, Issue 2, 28 October 2018, Pages 378-384
نویسندگان
Zekun Wang, Jingmei Song, Lingfei Luo, Jianlong Ma,