کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9018099 | 1128687 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells
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کلمات کلیدی
DMT1EMSAIRPSL-ferritinIRESDFXPKCHIF-1αLIPTFRROS - ROSElectrophoretic mobility shift assay - آزمون تحرک تحرک الکتروفورزIron - آهنaconitase - آکنیتازMitochondrial aconitase - آکنیتاز میوکاردریزیLabile iron pool - استخر چربFerritin Light Chain - زنجیره فراترین نورiron-responsive elements - عناصر پاسخ دهنده آهنdivalent metal transporter-1 - فلات دوالانت فلزی 1Nickel - نیکلhypoxia-inducible factor-1 alpha - هیپوکسی القاء عامل 1 آلفاiron-regulatory proteins - پروتئین های تنظیم کننده آهنProtein kinase C - پروتئین کیناز سیReactive oxygen species - گونههای فعال اکسیژنtransferrin receptor - گیرنده انتقالین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1α). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic selection pressure to convert a normal initiated cell into a cancer cell.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 206, Issue 3, 15 August 2005, Pages 275-287
Journal: Toxicology and Applied Pharmacology - Volume 206, Issue 3, 15 August 2005, Pages 275-287
نویسندگان
Haobin Chen, Todd Davidson, Steven Singleton, Michael D. Garrick, Max Costa,