Ekstraselüler asiditenin oksidatif strese karşı koruyuculuğunda otofaji ve apoptozun etkisi

Yıl 2025, Cilt: 50 Sayı: 3, 919 - 929, 30.09.2025

Nur Kaluç , Damla Koyun , Pınar Buket Demırel

https://doi.org/10.17826/cumj.1754448

Öz

Amaç: Bu çalışmada, ekstraselüler asiditenin oksidatif stres direncine ve hücre ölüm yolaklarına etkileri Saccharomyces cerevisiae modelinde ilk kez araştırılmıştır.
Gereç ve Yöntem: S. cerevisiae hücreleri normal ve asidik pH’a sahip ortamlarda kültüre edilerek 8 mM hidrojen peroksit (H₂O₂) ile oksidatif strese maruz bırakıldı. Hücre canlılığı, reaktif oksijen türleri (ROS) birikimi, apoptotik hücre oranları ve otofajik aktivite, CFU sayımı, floresan boyama ve mikroskopi yöntemleriyle değerlendirildi. Ayrıca, apoptoz ve otofaji ile ilişkili genetik mutantlar kullanılarak bu süreçlerin stres yanıtındaki rolleri araştırıldı.
Bulgular: Asidik ortamda bulunan hücreler, oksidatif strese karşı daha yüksek hayatta kalma oranı gösterdi. Bu durum, daha düşük ROS düzeyleri (%18,35’ten %2,44’e), daha düşük apoptoz oranları (%21,06’dan %12,45’e) ve artan MDC floresan oranı (97,68’den 115,48’e) ile doğrulandı. Ayrıca, 30 dakikalık H₂O₂ maruziyeti sonrasında CFU kat değişimi oranı, asidik koşullarda 0,031’den 0,181’e yükseldi. Asidik ortamda oksidatif strese maruz bırakılan mutant suşlarda CFU kat değişim oranları yca1Δ (0,172), atg4Δ (0,215) ve atg8Δ (0,153) suşlarında yabanıl tipe (0,103) kıyasla daha yüksek bulunmuştur. Bu bulgular, hem apoptoz hem de otofaji yolaklarının asidik koşullarda oksidatif stres yanıtına katkı sağladığını göstermektedir.
Sonuç: Bu bulgular, asidik mikroçevrenin hücre kaderini nasıl etkilediğine dair yeni bilgiler sunmakta olup, oksidatif stres ve doku asidozu ile ilişkili hastalıklarda tedavi stratejileri açısından önemli bir hedef olabileceğini göstermektedir.

Anahtar Kelimeler

apoptoz , ekstraselüler asidite , oksidatif stress , otofaji , Saccharomyces cerevisiae

Autophagy and apoptosis in the oxidative stress protection of extracellular acidity

Öz

Purpose: This study aimed to investigate the impact of extracellular acidity on oxidative stress resistance and to explore the interplay between apoptosis and autophagy on Saccharomyces cerevisiae.
Materials and Methods: Cells were cultured under either standard or acidic media and exposed to 8 mM hydrogen peroxide (H₂O₂) to induce oxidative stress. Cell viability, intracellular reactive oxygen species (ROS) levels, apoptotic cell ratio, and autophagolysosomes were evaluated by colony-forming unit (CFU) assay, fluorescence-based staining techniques, and microscopy. Mutant strains deficient in key genes in apoptosis and autophagy were utilized to evaluate specific contributions of these pathways to oxidative stress resistance.
Results: Cells cultured in the acidic environment showed resistance to oxidative stress. The CFU fold change ratios after 30 minutes of exposure were increased from 0.031 to 0.181, ROS levels were reduced from 18.35% to 2.44%, apoptotic cell ratios were decreased from 21.06% to 12.45%, and autophagic activities were increased from 97.68 to 115.48. In mutant strains subjected to oxidative stress in acidic media, CFU fold change ratios were also higher in yca1Δ (0.172), atg4Δ (0.215), and atg8Δ (0.153) compared to wild-type cells (0.103), indicating that both apoptosis and autophagy pathways contribute to the oxidative stress response under acidic conditions.
Conclusion: These findings provide novel insights into the influence of acidic microenvironments on cellular stress responses and may contribute to the development of therapeutic strategies for diseases associated with oxidative damage and tissue acidosis.

Anahtar Kelimeler

apoptosis , extracellular acidity , oxidative stress , autophagy , Saccharomyces cerevisiae

Destekleyen Kurum

Maltepe University

Kaynakça

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