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OKSİDATİF DNA HASARI VE YAŞLANMA

Journal Name:

  • Cerrahpaşa Tıp Dergisi

Publication Year:

  • 2004

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Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Reactive oxygen species (ROS) are formed in all living organisms as a by-product of normal metabolism and as a consequence of exposure to environmental agents. ROS attack on DNA generates a multiplicity of DNA damage products, including modified bases. One of the most common oxidative DNA lesions is 8-hydroxy deoxyguanosine (8OHdG). 8OHdG is regarded as a biomarker of oxidative DNA damage. This lesion induces G/C to T/A transversion mutation during replication of DNA. Results.- Mitochondria are both a major source of oxidants and a target for their damaging effects. Accumulation of oxidative mtDNA lesions plays a major role in mitochondrial dysfunction in aging. Specifically, the age-associated mitochondrial DNA deletions focally accumulate in postmitotic brain and skeletal muscle. The rate of mitochondrial ROS generation in post-mitotic tissues is negatively correlated with longevity in animals. Decrease in bioenergy, organ dysfunction and apoptosis are consequences of mitochondrial dysfunction .Apoptosis occurring under conditions of augmented and persistent oxidative stress is known to be increased in age associated Alzheimer’s disease or Parkinson.
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Abstract (Original Language): 
Tüm organizmalarda, normal metabolizma ve çevresel ajanlara maruz kalma sonucunda reaktif oksijen metabolitleri (ROM) oluşur. ROM’un DNA’ya etkisi sonucunda çok çeşitli DNA hasar ürünleri oluşur. Günümüzde 8-hid-roksi deoksiguanozin (8OHdG) oksidatif DNA hasarının göstergesi olarak kabul edilmektedir. En fazla oluşan oksidatif DNA lezyonlarından biri olan 8OHdG, DNA replikasyonu esnasında G/C, T/A transversion mutasyonuna neden olur. ROM’un hem başlıca oluşum yerleri hem de hasar yapıcı etkilerinin en önemli hedefleri mitokondrilerdir. Yaşlanma ile biriktiği sapta-nan oksidatif mitokondrial DNA (mtDNA) lez-yonları mitokondriyal fonksiyon bozukluğunun başlıca nedenidir. Özellikle yaşla artan mtDNA delesyonları post-mitotik beyin ve iskelet ka-sında birikime uğramaktadır. Post-mitotik do-kularda mitokondride ROM oluşum hızının hayvanlarda yaşam süresi ile ters ilişkili oldu-ğu saptanmıştır. Mitokondri disfonksiyonu bi-yoenerjide azalma, organ disfonksiyonu ve apoptoz ile sonuçlanır. Şiddetli ve kalıcı oksi-datif stres varlığında gerçekleşen apoptoz yaş-lanma ile insidensi artan Alzeimer Hastalığı ve Parkinson gibi hastalıklarda artmaktadır. Mitokondrial ROM oluşumunu ve DNA ha-sarını azaltan kalori kısıtlaması yaşlanma hızı-nı azaltan tek deneysel manipülasyondur.
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  • 4
159-169
  • Turkish

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