کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8301803 | 1537712 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of the interaction of human 5-lipoxygenase with its activating protein FLAP
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
DAPI5-H(P)ETELTB4GSHPBSamino acid - آمینو اسیدArachidonic acid - اسید آراشیدونیکinflammation - التهاب( توروم) Flap - برآافزا diamidino-2-phenylindole - دیامیدینو 2-فنیلینولDulbecco's phosphate-buffered saline - فسفات باسیل نمک Dulbeccophosphatidylcholine - فسفاتیدیل کولینLeukotrienes - لکوتری هاLeukotriene - لکوترینlipoxygenase - لیپواکسیژنازSubcellular localization - محلی سازی سلولwildtype - نوع وحشی5-Lipoxygenase-activating protein - پروتئین فعال 5-لیپوکسیژنازreduced glutathione - کاهش گلوتاتیون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Human 5-lipoxygenase (5-LO) is the key enzyme in the formation of leukotrienes (LTs), important mediators of inflammation. Cellular 5-LO activity is regulated in a complex manner, e.g. by calcium influx, the cellular redox status or 5-LO phosphorylation. Being a mobile enzyme, 5-LO migrates from the cytosol to the nuclear envelope where it is believed to interact with 5-lipoxygenase-activating protein (FLAP) and receives the substrate arachidonic acid (AA). 5-LO contains four cysteine residues located close to the AA entry site. In the present study, we show that in vitro glutathionylation of recombinant purified 5-LO wildtype (WT) as well as 5-LO 4C, a mutant where the four surface cysteines are replaced by serines (Cys159/300/416/418Ser), does not alter the product synthesis. However, in 5-LO/FLAP-transfected HeLa cells, treatment with the thiol-oxidizing agent diamide which promotes glutathionylation at surface Cys residues led to a decreased LT synthesis by 5-LO WT. In contrast to the WT enzyme, LT formation of the 4C mutant was stimulated by addition of diamide. Immunofluorescence studies in human monocytes and HEK293 cells, expressing 5-LO and FLAP, revealed that diamide prevented the translocation of 5-LO WT whereas it enhanced the translocation of the fourfold cysteine mutant. Therefore, we could demonstrate that the interface, involving the four cysteines 159, 300, 416 and 418, is important for the translocation to the nuclear membrane and the colocalization with FLAP.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1851, Issue 11, November 2015, Pages 1465-1472
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1851, Issue 11, November 2015, Pages 1465-1472
نویسندگان
Ann-Kathrin Häfner, Jana Gerstmeier, Michael Hörnig, Sven George, Ann-Katrin Ball, Mirjam Schröder, Ulrike Garscha, Oliver Werz, Dieter Steinhilber,