کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738734 | 1046751 | 2009 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Differential genomic and proteomic profiling of glioblastoma cells exposed to terpyridineplatinum(II) complexes
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کلمات کلیدی
TrxTNB−rRNAN-myc downstream-regulated gene 1Cyclin E1CCNE1Eukaryotic initiation factor 5aNDRG1CCNB1Cyclin B1STMN1EIF5Aselenophosphate synthetase 2SPS2TrxRtPCSDTNBFASGPXGAPDHPMFSAMATFRibosomal RNA - RNA RibosomalCHCA - آنها می خواهندPeptide mass fingerprint - اثر انگشت پپتیدهStathmin 1 - استاتمیم 1Bax - باکسSignificance Analysis of Microarrays - تجزیه و تحلیل اهمیت Microarraysthioredoxin reductase - تریودوکسین ردوکتازthioredoxin - تیرودوکسینDouble stranded - دو رشتهFree radicals - رادیکال آزادMicroarray - ریزآرایهSOD - سدSuperoxide dismutase - سوکسوکس دیسموتازPlatinum complexes - مجتمع های پلاتینProteomics - پروتئومیکسPERK - پرکglutathione reductase - گلوتاتیون ردوکتازglutathione peroxidase - گلوتاتیون پراکسیدازglyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژنازGlioblastoma - گلیوبلاستوما
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Terpyridineplatinum(II) complexes (TPCs) efficiently inhibit the proliferation of glioblastoma cells in vitro and have been tested successfully in a rodent glioblastoma model. Apart from intercalation with DNA, the major mechanism of action of TPCs is a very potent and specific interaction with the human selenoprotein thioredoxin reductase (TrxR). TrxR plays a crucial role in cellular redox homeostasis and protection against oxidative damage. In many malignant cells the thioredoxin system is upregulated, promoting tumor growth and progression. Thus, the thioredoxin system has been proposed to be an attractive target for cancer therapy. This study gives the first comprehensive overview of the effects of TPCs on the transcriptome and proteome of glioblastoma cells. We reveal that under TPC treatment, mechanisms countersteering TrxR inhibition are activated in parallel to DNA-damage-responsive pathways. TPC pressure results in long-term compensatory upregulation of TrxR expression. In parallel, p53 is activated, leading to a range of regulations typical for cell-cycle-arrested cells such as upregulation of CDKN1A, induction of GADD45, inhibition of eIF5A maturation, and reduced phosphorylation of stathmin. We also show that TPCs induce endoplasmic reticulum stress, as they activate the unfolded protein response. This profiling study provides a thorough insight into the spectrum of cellular events resulting from specific TrxR inhibition and characterizes the TPC mode of action.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 46, Issue 8, 15 April 2009, Pages 1096-1108
Journal: Free Radical Biology and Medicine - Volume 46, Issue 8, 15 April 2009, Pages 1096-1108
نویسندگان
Sasa Koncarevic, Sabine Urig, Klaus Steiner, Stefan Rahlfs, Christel Herold-Mende, Holger Sueltmann, Katja Becker,