کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5562620 1562703 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of reductase systems by 2-AAPA modulates peroxiredoxin oxidation and mitochondrial function in A172 glioblastoma cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Inhibition of reductase systems by 2-AAPA modulates peroxiredoxin oxidation and mitochondrial function in A172 glioblastoma cells
چکیده انگلیسی
Thiol homeostasis has a critical role in the maintenance of proper cellular functions and survival, being coordinated by the action of several reductive enzymes, including glutathione (GSH)/glutathione reductase (GR) and thioredoxin (Trx)/thioredoxin reductase (TrxR) systems. Here, we investigated the effects of the GR inhibitor 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) on the activity of thiol reductases (GR and TrxR), redox balance and mitochondrial function of A172 glioblastoma cells. 2-AAPA inhibited cell GR (IC50 = 6.7 μM) and TrxR (IC50 = 8.7 μM). A significant decrease in the cellular ability to decompose cumene hydroperoxide was observed and associated to a greater susceptibility to this peroxide. The redox state of peroxiredoxins (Prx1, Prx2 and Prx3) was markedly shifted to dimer 30 min after treatment with 100 μM 2-AAPA, an event preceding 2-AAPA-induced decrease in cell viability. Furthermore, mitochondrial function was also severely impaired, leading to a decrease in the respiratory control ratio, reserve capacity, and ATP synthesis-coupled respiration, as well as an increase in mitochondrial membrane potential. Our results indicate that inhibition of GR and TrxR activities, disruption of the ability to detoxify peroxides, increased oxidation of Prxs, as well as compromised mitochondrial function represent early events mediating 2-AAPA toxicity to A172 glioblastoma cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 42, August 2017, Pages 273-280
نویسندگان
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