کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833843 | 1065829 | 2011 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pathogenesis of aortic dilatation in mucopolysaccharidosis VII mice may involve complement activation
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کلمات کلیدی
Mucopolysaccharidosis VIIGAGsα-L-iduronidaseIDUATLR4M6PSTAT3GUSBAmCTBSVVGCTSIL-6MMPPBSTNFα7-amino-4-methylcoumarin - 7-آمینو-4-متیل کومارینβ-glucuronidase - β-گلوکورونیدازenzyme replacement therapy - آنزیم جایگزین درمانAortic dilatation - انقباض آئورتinterleukin 6 - اینترلوکین 6Retroviral vector - بردار RetroviralTris-buffered saline - تریس بافر شورtumor necrosis factor alpha - تومور نکروز عامل آلفاComplement system - دستگاه کمپلمان، سیستم کمپلمانPhosphate buffered saline - فسفات بافر شورBlood pressure - فشارخونmatrix metalloproteinase - ماتریکس متالوپروتئینازMatrix metalloproteinase 12 - ماتریکس متالوپروتئیناز 12mannose 6-phosphate - مانوس 6-فسفاتsignal transducer and activator of transcription 3 - مبدل سیگنال و فعال کننده رونویسی 3Mucopolysaccharidosis - موکوپلیساکاریدوزMPs - نمایندگان مجلسERT - هستندGene therapy - ژن درمانیCathepsin S - کاتهپسین SCathepsin - کاتپسینGlycosaminoglycans - گلیکوز آمینو گلیکان هاToll-like receptor 4 - گیرنده تله مانند 4
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme β-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation, which is associated with upregulation of the elastases cathepsin S (CtsS) and matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII mice were crossed with mice deficient in CtsS or MMP12, and the effect upon aortic dilatation was determined. CtsS deficiency did not protect against aortic dilatation in MPS VII mice, but also failed to prevent an upregulation of cathepsin enzyme activity. Further analysis with substrates and inhibitors specific for particular cathepsins suggests that this enzyme activity was due to CtsB, which could contribute to elastin fragmentation. Similarly, MMP12 deficiency and deficiency of both MMP12 and CtsS could not prevent aortic dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR were performed to look for upregulation of other elastases. This demonstrated that mRNA for complement component D was elevated in MPS VII mice, while immunostaining demonstrated high levels of complement component C3 on surfaces within the aortic media. Finally, we demonstrate that neonatal intravenous injection of a retroviral vector encoding β-glucuronidase reduced aortic dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement component D may be involved. Complement may be activated by the GAGs that accumulate, and may play a role in signal transduction pathways that upregulate elastases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 104, Issue 4, December 2011, Pages 608-619
Journal: Molecular Genetics and Metabolism - Volume 104, Issue 4, December 2011, Pages 608-619
نویسندگان
Guilherme Baldo, Susan Wu, Ruth A. Howe, Meera Ramamoothy, Russell H. Knutsen, Jiali Fang, Robert P. Mecham, Yuli Liu, Xiaobo Wu, John P. Atkinson, Katherine P. Ponder,