Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells
المؤلفون المشاركون
Tiribelli, Claudio
Rawat, Vipin
Bortolussi, Giulia
Gazzin, Silvia
Muro, Andrés F.
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-11، 11ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-11-26
دولة النشر
مصر
عدد الصفحات
11
التخصصات الرئيسية
الملخص EN
Unconjugated bilirubin is considered a potent antioxidant when present at moderate levels.
However, at high concentrations, it produces severe neurological damage and death associated with kernicterus due to oxidative stress and other mechanisms.
While it is widely recognized that oxidative stress by different toxic insults results in severe damage to cellular macromolecules, especially to DNA, no data are available either on DNA damage in the brain triggered by hyperbilirubinemia during the neonatal period or on the activation of DNA repair mechanisms.
Here, using a mouse model of neonatal hyperbilirubinemia, we demonstrated that DNA damage occurs in vivo in the cerebellum, the brain region most affected by bilirubin toxicity.
We studied the mechanisms associated with potential toxic action of bilirubin on DNA in in vitro models, which showed significant increases in DNA damage when neuronal and nonneuronal cells were treated with 140 nM of free bilirubin (Bf), as determined by γH2AX Western blot and immunofluorescence analyses.
Cotreatment of cells with N-acetyl-cysteine, a potent oxidative-stress inhibitor, prevented DNA damage by bilirubin, supporting the concept that DNA damage was caused by bilirubin-induced oxidative stress.
Bilirubin treatment also activated the main DNA repair pathways through homologous recombination (HR) and nonhomologous end joining (NHEJ), which may be adaptive responses to repair bilirubin-induced DNA damage.
Since DNA damage may be another important factor contributing to neuronal death and bilirubin encephalopathy, these results contribute to the understanding of the mechanisms associated with bilirubin toxicity and may be of relevance in neonates affected with severe hyperbilirubinemia.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Rawat, Vipin& Bortolussi, Giulia& Gazzin, Silvia& Tiribelli, Claudio& Muro, Andrés F.. 2018. Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1210920
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Rawat, Vipin…[et al.]. Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-11.
https://search.emarefa.net/detail/BIM-1210920
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Rawat, Vipin& Bortolussi, Giulia& Gazzin, Silvia& Tiribelli, Claudio& Muro, Andrés F.. Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1210920
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1210920
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر