کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9886637 | 1537841 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
eLOX3hydro(pero)xyeicosatetraenoic acidEpoxyalcoholRP-HPLCKETEtrimethylsilylLC-ESI-MSTMSGC-MS - کروماتوگرافی گازی-طیف سنج جرمیH(P)ETE - H (P) ETELOX - اکسیژن مایعichthyosis - ایشتیوزmutation - جهشlipoxygenase - لیپواکسیژنازHepoxilin - هپکسیلینEpoxide hydrolase - هیدرولاز اپوکسیSkin - پوستKeratocyte - کراتوسایتreversed-phase high pressure liquid chromatography - کروماتوگرافی مایع با فشار فاز معکوسGas Chromatography-Mass Spectrometry - گاز کروماتوگرافی-اسپکترومتری جرمی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Non-bullous congenital ichthyosiform erythroderma (NCIE) is one of the main clinical forms of ichthyosis. Genetic studies indicated that 12R-lipoxygenase (12R-LOX) or epidermal lipoxygenase-3 (eLOX3) was mutated in six families affected by NCIE [F. Jobard, C. Lefèvre, A. Karaduman, C. Blanchet-Bardon, S. Emre, J. Weissenbach, M. Ãzgüc, M. Lathrop, J.F. Prud'homme, J. Fischer, Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1, Hum. Mol. Genet. 11 (2002) 107-113.], but the impact of these mutations on LOX function has not been defined. To explore this, we overexpressed the wild-type or mutated enzymes in E. coli and COS7 cells and then analyzed the essential catalytic properties. We showed recently that human eLOX3 is a hydroperoxide isomerase (hepoxilin synthase) that converts the product of 12R-LOX, 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE) to a specific epoxyalcohol. Using incubations with [14C]-labeled substrates and HPLC analyses, we found that the naturally occurring mutations totally eliminate the lipoxygenase activity of 12R-LOX and the hydroperoxide isomerase activity of eLOX3. We further demonstrate that the 12R-LOX/eLOX3-derived 8R-hydroxy-11R,12R-epoxide is converted by an epoxide hydrolase in COS7 cells and in human keratinocytes to a single isomer of 8,11,12-trihydroxyeicosa-5,9,14-trienoic acid. Taken together, the results support the hypothesis that 12R-LOX, eLOX3, and perhaps an epoxide hydrolase function together in the normal process of skin differentiation, and that the loss of function mutations are the basis of the LOX-dependent form of NCIE.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1686, Issue 3, 5 January 2005, Pages 238-247
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1686, Issue 3, 5 January 2005, Pages 238-247
نویسندگان
Zheyong Yu, Claus Schneider, William E. Boeglin, Alan R. Brash,