کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738441 | 1046705 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Maintenance of immune hyporesponsiveness to melanosomal proteins by DHICA-mediated antioxidation: Possible implications for autoimmune vitiligo
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کلمات کلیدی
DHICATYRP1DcT2′,7′-dichlorofluorescin diacetate - 2 '، 7'-dichlorofluorescin diacetate5,6-dihydroxyindole-2-carboxylic acid - 5،6-دی هیدروکسی اندول-2-کربوکسیلیک اسیدH2DCFDA - H2DCFD بهROS - ROSAntioxidation - آنتی اکسید شدنImmunogenicity - ایمنی زاییdHI - بزdopachrome tautomerase - تاتومراز dopachromeTyr - تیرTyrosinase - تیروزیناز Free radicals - رادیکال آزادtyrosinase-related protein 1 - پروتئین مرتبط با تیروزیناز 1vitiligo - پیسی، برص، لک و پیس، ویتیلیگوReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Melanocyte destruction in the skin of vitiligo patients has been considered to be a consequence of an autoimmune response against melanosomal proteins. However, little is known about the molecular mechanisms by which the immune system recognizes these sequestered intracellular self-proteins, which are confined in specialized organelles termed melanosomes, and is provoked into an autoimmune response to melanocytes. Here, we utilize a sucrose density-gradient ultracentrifugation protocol to enrich melanosomal components from dopachrome tautomerase (Dct)-mutant or wild-type melanocytes exposed to a pulse of hydrogen peroxide at a noncytotoxic concentration to evaluate their immunogenicity in mice challenged with the corresponding melanosomal proteins. The results demonstrate that enhanced humoral and cellular immune responses to a challenge with late-stage melanosomal proteins, especially with those derived from Dct-mutant melanocytes, are found in the immunized mice. To elucidate whether a reduced 5,6-dihydroxyindole-2-carboxylic acid (DHICA) content in melanin might cause a loss in antioxidative protection to the proteins, we incubated these melanosomal proteins in vitro with synthetic 5,6-dihydroindole (DHI)-melanin or DHI/DHICA (1:1)-melanin and then used them to immunize mice. T cell proliferation and IgG antibody responsiveness to the challenges were significantly induced by melanosomal proteins treated with DHI-melanin, but not by those treated with DHI/DHICA (1:1)-melanin. Moreover, we observed that melanosomal proteins derived from Dct-mutant melanocytes are subject to oxidative modifications that alter their antigenic configurations to attain an enhanced immunogenicity compared with those derived from wild-type melanocytes. From these results, we conclude that DHICA-mediated antioxidation plays a critical role in the maintenance of immune hyporesponsiveness to melanosomal proteins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 50, Issue 9, 1 May 2011, Pages 1177-1185
Journal: Free Radical Biology and Medicine - Volume 50, Issue 9, 1 May 2011, Pages 1177-1185
نویسندگان
Xiao-Ming Liu, Qiong Zhou, Shi-Zheng Xu, Kazumasa Wakamatsu, Tie-Chi Lei,