کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738383 | 1046704 | 2011 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endothelial nitric oxide synthase uncoupling as a key mediator of melanocyte malignant transformation associated with sustained stress conditions
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کلمات کلیدی
phorbol 12-myristate 13-acetateDAHPDAF-2DAGTP cyclohydrolase ItetrahydrobiopterinDnmtBH4flavin adenine dinucleotideFMNBH2MnSODNOS2,4-diamino-6-hydroxypyrimidine - 2،4-دیامینو-6-هیدروکسی پوریمیدینDNA methyltransferase - DNA متیل ترانسفرازl-NAME - L-NAMEl-NG-Nitroarginine methyl ester - L-NG-Nitroarginine متیل استرPMA - LDC هاPTIO - ptioROS - ROSAnoikis - آنوکیسsuperoxide anion - آنیون سوپر اکسیدeNOS uncoupling - انحلال ENOSFAD - بدMalignant transformation - تحول بدخیمdihydrobiopterin - دی هیدروبیوپترینdihydroethidium - دی هیدروتیدیمFree radicals - رادیکال آزادmanganese superoxide dismutase - سوپر اکسید دیسموتاز منگنزVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)flavin mononucleotide - فلاون مونونوکلئوتیدmelanocytes - ملانوسیت هاnitric oxide synthase - نیتریک اکسید سنتازDHE - وReactive 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
Melanoma cell lines and cells corresponding to premalignant melanocytes were established by our group after subjecting a nontumorigenic murine melanocyte lineage, melan-a, to sequential cycles of anchorage blockade. Previous results showed that in melan-a cells the superoxide level increases after such procedure. Superoxide production during melanocyte de-adhesion was inhibited by L-sepiapterin, the precursor of eNOS cofactor BH4, and increased by the inhibitor of BH4 synthesis, DAHP, hence indicating a partial uncoupling state of eNOS. The eNOS uncoupling seems to be maintained in cells derived from melan-a, because they present decreased nitric oxide and increased superoxide levels. The inhibition of superoxide production in Tm5 melanoma cells with L-sepiapterin reinforces their eNOS-uncoupled state. The maintenance of oxidative stress seems to be important in melanoma apoptosis resistance because Mn(III)TBAP, a superoxide scavenger, or L-sepiapterin renders Tm5 cells more sensitive to anoikis and chemotherapy. More importantly, eNOS uncoupling seems to play a pivotal role in melanocyte malignant transformation induced by sustained anchorage impediment, because no malignant transformation was observed when L-NAME-treated melanocytes were subjected to sequential cycles of de-adhesion. Our results show that uncoupled eNOS contributes to superoxide production during melanocyte anchorage impediment, contributing to anoikis resistance and malignant transformation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 50, Issue 10, 15 May 2011, Pages 1263-1273
Journal: Free Radical Biology and Medicine - Volume 50, Issue 10, 15 May 2011, Pages 1263-1273
نویسندگان
Fabiana H.M. Melo, Fernanda Molognoni, Alice S. Morais, Mariana Toricelli, Margareth G. Mouro, Elisa M.S. Higa, José D. Lopes, Miriam G. Jasiulionis,