کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1911445 | 1046817 | 2007 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The role of ascorbate in the modulation of HIF-1α protein and HIF-dependent transcription by chromium(VI) and nickel(II)
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کلمات کلیدی
pVHLCA9dehydroascorbateHREHIF-1αHIF2-OG - 2 و2-oxoglutarate - 2-اگزوگلوتراتROS - ROSAscorbate - آسکوربات یا ویتامین ثvon Hippel–Lindau protein - از پروتئین Hippel-LindauDHA - دوکوساهگزائنوئیک اسیدFree radicals - رادیکال آزادhypoxia-inducible transcription factor - عامل رونویسی القایی هیپوکسیNickel(II) - نیکل(II)Carbonic anhydrase 9 - کربن انیدراز 9Chromium(VI) - کروم (VI)Reactive 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
Molecular oxygen is involved in hydroxylation and subsequent degradation of HIF-1α, a subunit of HIF-1 transcription factor; therefore oxygen shortage (hypoxia) stabilizes this protein. However, HIF-1α can also be stabilized by transition metal ions in the presence of oxygen, suggesting that a different mechanism is involved in metal-induced hypoxic stress. Recently, we showed that the depletion of intracellular ascorbate by metals may lead to the inhibition of hydroxylases. Because nickel(II) has similarity to iron(II), an alternative hypothesis suggests that iron substitution for nickel in the enzyme inhibits hydroxylase activity. Here we investigated the induction of HIF-1 by another metal, chromium, which cannot replace iron in the enzyme. We show that chromium(VI), but not chromium(III), can oxidize ascorbate both in cells and in a cell-free system. In agreement with these data chromium(VI) stabilizes HIF-1α protein in cells only until it is reduced to chromium(III). In contrast, nickel(II) was found to be a catalyst, which facilitated continuous oxidation of ascorbate by ambient oxygen. These data correlate with extended stabilization of HIF-1α after acute exposure to nickel(II). The HIF-1-dependent reporter assays revealed that 20-24 h was required to fully develop the HIF-1 transcriptional response, and the acute exposure to nickel(II), but not chromium(VI), meets this requirement. However, repeated (chronic) exposure to chromium(VI) can also lead to extended stabilization of HIF-1α. Thus, the obtained data emphasize the important role of ascorbate in regulation of HIF-1 transcriptional activity in metal-exposed human lung cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 42, Issue 8, 15 April 2007, Pages 1246-1257
Journal: Free Radical Biology and Medicine - Volume 42, Issue 8, 15 April 2007, Pages 1246-1257
نویسندگان
Monika Kaczmarek, Olga A. Timofeeva, Aldona Karaczyn, Anatoli Malyguine, Kazimierz S. Kasprzak, Konstantin Salnikow,