Pınar KÖSEOĞLU, Gamze GÜVEN, Ebba LOHMANN, Haşmet HANAĞASI, Hakan GÜRVİT, Başar BİLGİÇ, İrem DİKER, Nihan ERGİNEL-UNALTUNA

Alzheimer Hastalığında Oksidatif Stres ile İlişkili Seçilmiş Genlerin Periferik Kandaki Anlatım Düzeyi

Amaç: Oksidatif stres, Alzheimer hastalığının (AH) etiyolojisinde önemli bir rol oynamaktadır. Antioksidan enzimler reaktif oksijen türevlerinin (ROS) hücreye zarar vermesini önlemek için çok önemlidir. Oksidan ve antioksidan enzimleri kodlayan genlerin anlatım seviyelerindeki değişimler hücrenin oksidatif strese karşı verdiği yanıtta anahtar faktördür. Bu nedenle çalışmamızda, AH hastalarının periferik kanlarında spesifik oksidatif stres ile ilişkili genlerin (solut taşıyıcı aile 7 üye 11 (SLC7A11), glutatyon peroksidaz 4 (GPX4), katalaz (CAT ) ve açil koA sentetaz uzun zincir aile üyesi 4 (ACSL4)) anlatım düzeylerindeki değişimin araştırılması amaçlanmıştır.Gereç ve Yöntem: Periferik kan lökositlerinde oksidatif stresle ilgili genlerin ekspresyon düzeylerindeki değişiklikler 25 AH hastası ve 22 kontrolde kantitatif ters transkripsiyon polimeraz zincir reaksiyonu (qRT-PCR) ile belirlenmiş ve sonuçlar istatistiksel olarak değerlendirilmiştir.Bulgular:SLC7A11, GPX4, CAT ve ACSL4 genlerinin anlatım düzeyleri, AH hastaları ve kontroller arasında istatistiksel olarak bir farklılık göstermemiştir. Ayrıca, sonuçlarımız başlangıç yaşı ile ACSL4 ekspresyonu arasında anlamlı negatif bir korelasyon olduğunu göstermiştir.Sonuç: Araştırmamız, AH hastalarının periferik kanlarında SLC7A11, GPX4 ve ACSL4 genlerinin anlatım düzeylerini değerlendiren ilk çalışma olup, sonuçlarımız söz konusu genlerin periferik kandaki an-latımlarının AH'de değişmediğini göstermiştir. Bununla birlikte, az sayıda hasta ve kontrol nedeniyle, bu bulgular başlangıç niteliğindedir ve daha geniş çalışma gruplarında doğrulanması gerekmektedir.

Anahtar Kelimeler:

Alzheimer hastalığı, oksidatif stres, SLC7A11, GPX4, CAT, ACSL4

Peripheral Expression Levels of Selected Oxidative Stress-Related Genes in Alzheimer’s Disease

Objective: The etiology of Alzheimer's disease (AD) is affected via oxidative stress. Antioxidant enzymes are extremely important in preventing reactive oxygen species (ROS) causing damage in the cell. The changes in expression levels of oxidant and antioxidant genes are key factors in cell response to oxidative stress. As a result, this study investigated the change in expression levels of specif-ic oxidative stress related genes (solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), catalase (CAT ) and acyl-coa synthetase long chain family member 4 (ACSL4)) in peripheral blood of AD patients. Material and Method: Quantitative reverse-transcription poly-merase chain reaction (qRT-PCR) was used to assess the expression levels of oxidative stress-related genes in 25 AD patients and 22 controls, and the findings were statistically evaluated. Results:SLC7A11, GPX4, CAT, and ACSL4 gene expression levels did not vary significantly between AD patients and controls. The re-sults also showed significant negative correlation between age of onset and ACSL4 expression.Conclusion: This is the first study that evaluated mRNA expression levels of SLC7A11, GPX4 and ACSL4 genes in AD. The results sug-gested that the peripheral blood expression of above-mentioned genes did not alter in AD. However, due to the small number of subjects, this findings are preliminary and should be validated with a larger number of subjects.

Keywords:

Alzheimer’s Disease, oxidative stress, SLC7A11, GPX4, CAT, ACSL4,

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