کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8269281 | 1534958 | 2015 | 33 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prion protein functions as a ferrireductase partner for ZIP14 and DMT1
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کلمات کلیدی
FACFerrireductaseduodenal cytochrome BDcytBNTBIPrPcZIPDMT1LIPGFPTransferrinTFRIron - آهنFerric Ammonium Citrate - آهن آمونیوم سیتراتnon-transferrin-bound iron - آهن غیر انتقال سرمLabile iron pool - استخر چربSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدSodium dodecyl sulfate polyacrylamide gel electrophoresis - الکتروفورز ژل پلی اتیل آمید سدیم دودسیل سولفاتintraperitoneal - داخل صفاقیdivalent metal transporter-1 - فلات دوالانت فلزی 1green-fluorescent protein - پروتئین سبز فلورسنتPrion protein - پروتئین پریونLiver - کبدtransferrin receptor - گیرنده انتقالین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound iron (NTBI) and transferrin (Tf) iron at the plasma membrane and endosomes, respectively, by ferrireductase (FR) proteins for transport across biological membranes through divalent metal transporters. Here, we report that prion protein (PrPC), a ubiquitously expressed glycoprotein most abundant on neuronal cells, functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14. Thus, absence of PrPC in PrP-knock-out (PrP-/-) mice resulted in markedly reduced liver iron stores, a deficiency that was not corrected by chronic or acute administration of iron by the oral or intraperitoneal routes. Likewise, preferential radiolabeling of circulating NTBI with 59Fe revealed significantly reduced uptake and storage of NTBI by the liver of PrP-/- mice relative to matched PrP+/+ controls. However, uptake, storage, and utilization of ferritin-bound iron that does not require reduction for uptake were increased in PrP-/- mice, indicating a compensatory response to the iron deficiency. Expression of exogenous PrPC in HepG2 cells increased uptake and storage of ferric iron (Fe3+), not ferrous iron (Fe2+), from the medium, supporting the function of PrPC as a plasma membrane FR. Coexpression of PrPC with ZIP14 and DMT1 in HepG2 cells increased uptake of Fe3+ significantly, and surprisingly, increased the ratio of N-terminally truncated PrPC forms lacking the FR domain relative to full-length PrPC. Together, these observations indicate that PrPC promotes, and possibly regulates, the uptake of NTBI through DMT1 and Zip14 via its FR activity. Implications of these observations for neuronal iron homeostasis under physiological and pathological conditions are discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 84, July 2015, Pages 322-330
Journal: Free Radical Biology and Medicine - Volume 84, July 2015, Pages 322-330
نویسندگان
Ajai K. Tripathi, Swati Haldar, Juan Qian, Amber Beserra, Srinivas Suda, Ajay Singh, Ulrich Hopfer, Shu G. Chen, Michael D. Garrick, Jerrold R. Turner, Mitchell D. Knutson, Neena Singh,