کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1912993 1535094 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidative stress-induced apoptosis in peripheral blood lymphocytes from patients with POLG-related disorders
ترجمه فارسی عنوان
آپوپتوز ناشی از استرس اکسیداتیو در لنفوسیتهای خون محیطی از بیماران مبتلا به اختلالات مرتبط با پلیگ
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی


• Increased oxidative stress-induced apoptosis in PBLs of POLG patients
• Deficit in POLG may increase sensitivity to the effects of oxidative stress.
• Apoptosis may play a pathogenetic role in POLG-related diseases.

BackgroundPOLG-related disorders are a group of heterogeneous diseases characterized by an overlapping clinical presentations and associated with mutations in the POLG gene. POLG codes for the catalytic subunit of mitochondrial polymerase gamma (POLG), essential for mitochondrial DNA (mtDNA) replication and repair.Studies on mutator POLG mice showed an increase in oxidative stress and apoptosis.In this regard we analysed the involvement of POLG mutations in the apoptotic regulation, evaluating apoptosis in peripheral blood lymphocytes (PBLs) from patients with POLG-related diseases.MethodsCells were cultured under basal conditions and with 2-deoxy-d-ribose (dRib), a reducing sugar that induces apoptosis by oxidative stress. Apoptosis rate was assessed by flow cytometry. Phosphatidylserine translocation, mitochondrial membrane depolarization and caspase 3 activation were also analysed.ResultsOur data showed higher percentages of apoptosis after dRib treatment in patients with POLG mutations than in controls, while under basal culture conditions, apoptosis levels were similar in the two groups.ConclusionsCells with POLG mutations are more sensitive than control cells to oxidative stress-induced apoptosis, confirming that mtDNA mutations may have a role in mitochondrial apoptosis pathway. We also suggest that redox state homeostasis may play a crucial role in phenotypic expression of POLG-related diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the Neurological Sciences - Volume 368, 15 September 2016, Pages 359–368
نویسندگان
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