Tetraconazole-induced Programmed Cell Death in Schizosaccharomyces pombe

Yıl 2021, Cilt: 8 Sayı: 2, 833 - 843, 31.12.2021

Hızlan Hıncal Ağuş , Ahsen Çetin İrem Naz Yalçın

https://doi.org/10.35193/bseufbd.963547

Cited By: 1

Öz

Tetraconazole, a systemic triazole fungicide, shows potential toxic effects in agriculture and human health. Therefore, its cytotoxic effects and accompanying mechanisms should be unraveled. S. pombe (ED666) was used in this study, as a unicellular biology and toxicology model. Cells were grown on standard media and all treatments were done at 30 C and shaking at 180 rpm 1-10 mg/L tetraconazole induced a dose-dependent cell death. Apoptosis was monitored by DAPI ve AO/EB staining. Excessive ROS production and mitochondrial impairment were shown by DCFDA/NBT assays and Rhodamine 123 staining, which were supported by increased expressions of superoxide dismutases and glutathione peroxidase. Involvement of one of the potential apoptotic genes, Cnx1, in apoptosis was shown by increased transcription whereas two other potential genes, Pca1 and Aif1, were not affected by tetraconazole treatment. In conclusion, tetraconazole-induced cytotoxicity and underlying mechanisms which were mediated via ROS damage and mitochondrial dysregulation (Cnx1-driven) were clarified in S. pombe.

Anahtar Kelimeler

Schizosaccharomyces Pombe, Tetraconazole, Apoptosis, Cnx1, Oxidative Damage

Destekleyen Kurum

İstanbul Yeni Yüzyıl Üniversitesi Mütevelli Heyeti

Teşekkür

This work was supported by Istanbul Yeni Yuzyil University. We specially thanks to Aysegul Topal-Sarikaya, Bedia Palabiyik for providing S. pombe cells, Sinem Tunçer Gurbanov and Emre Yoruk for consumables and chemicals.

Schizosaccharomycespombe’deTetrakonazol Kaynaklı Programlı Hücre Ölümü

Öz

Sistemik triazol bir fungisit olan tetrakonazol tarımda ve insan sağlığında potansiyel toksik etkiler göstermektedir. Bu yüzden, sitotoksik etkileri ve eşlik eden mekanizmaları açığa çıkarılmalıdır. Bu çalışmada, tek hücreli biyoloji ve toksikoloji modeli olarak S. pombe (ED666) kullanılmıştır. Hücreler standart medyumda büyütülmüş, muameleler 30 C’de ve 180 rpm hızda çalkalamalı olarak yapılmıştır. 1-10 mg/L tetrakonazol doz-bağımlı hücre ölümüne sebep olmuştur. Apoptoz DAPI ve AO/EB boyamasıyla görüntülenmiştir. Aşırı ROS üretimi ve mitokondriyel bozulma DCFDA/NBT deneyleri ve Rhodamin 123 boyamasıyla gösterilmiş, bu sonuçlar da süperoksitdismutazlar ve glutatyonperoksidaz ifadelerindeki artışlarla desteklenmiştir. Potansiyel apoptotik genlerden biri olan Cnx1’in apoptozla ilişkisi transkripsiyonundaki artışla gösterilirken, diğer iki potansiyel gen, Pca1 ve Aif1 tetrakonazolden etkilenmemiştir. Sonuç olarak, tetrakonazol kaynaklı apoptoz ile, ROS hasarı ve mitokondriyel düzensizliğin (Cnx1-yoluyla) aracılık etmiş olduğu mekanizmalar S. pombe’de açıklığa kavuşturulmuştur.

Anahtar Kelimeler

Schizosaccharomyces Pombe, Tetrakonazol, Apoptoz, Cnx1, Oksidatif Hasar

Kaynakça

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