MEHMET REŞİT TAYSI, BÜNYAMİN SÖĞÜT, Victor S. NEDZVETSKY, MUAMMER KIRICI, CAN ALİ AĞCA

İnorganik Civanın Subletal Dozlarının Gökkuşağı Alabalığı (Oncorhynchus mykiss) Beyin Dokusunda Doza Bağlı RPA1 İçeriğini Yükseltmesi ve P53 Ekspresyonunu Engellemesi

Civa (Hg), su ortamının en toksik ve yaygın unsurlarından biridir. Hemen hemen her balık türü Hg’ ya maruz kaldığı zaman bunu dokularında biriktirebilir. Civa ile indüklenen hücresel fonksiyon bozukluğu, sucul ortamdaki kirlenme riskini tahmin etmek için yeterli biyobelirteç olarak kullanılabilir. Beyin hücreleri, civa bileşiklerinin sitoksisitesine karşı oldukça hassastır. Çeşitli civa türleri, beyin hücrelerinin hem yapısı hem de işlevi üzerinde farklı zararlı etkilere sahiptir. Son zamanlarda yapılan çalışmalarda inorganik civanın nörotoksisitesi tartışılmaya devam etse de tamamıyla incelenmemiştir. Bu çalışmada organik civanın subletal dozlarına maruz bırakılan gökkuşağı alabalığının beyin dokusunda rpa1 ve p53 proteinlerinin rolünü araştırdık. Sunulan çalışmada civa klorürün LD50 değeri, 96 saat maruz kalma ile 551 μg / L olarak belirlenmiştir. Gökkuşağı alabalıkları 2 ve 7 günlük zaman aralıklarında iki subletal doza maruz bırakıldı. Civa klorüre maruz bırakılan balıkların beyin dokusunda doz ve zaman bağımlı olarak ROS seviyesinde bir artış belirlenmiştir. Ayrıca, hem % 25 hem de % 50 LD50 civa dozlarına maruz kalma süresince RPA1 ekspresyonunun önemli ölçüde upregülasyonuna neden olmuştur. 2 gün süre ile Hg maruz bırakılan balıkların beyin dokusunda, p53 ekspresyonunu zayıf bir şekilde uyarmıştır. Bunun tam tersine olarak, 7 günlük maruz kalma, p53 ekspresyonunda önemli bir azalmaya neden oldu. Sunulan çalışmanın sonuçları inorganik civanın alt dozlarının son derece nörotoksik olduğunu ve stres sensörü proteini p53 ün azalması ile balık beyni sinyal yollarında bozukluğa neden olabileceğini kanıtlamaktadır. Ayrıca, RPA1 ekspresyonundaki artış, balıkların beyin hücrelerinin ROS kaynaklı DNA kırılmalarını tamir edebileceğini ve inorganik Hg'nin genotoksik etkisini önleyebileceğini göstermektedir. Genel olarak, mevcut veriler inorganik civaların balık beyin hücrelerine toksik olduğunu ve bu sorunun gelecekte de araştırılmasının gerekliliğine işaret etmektedir.

Anahtar Kelimeler:

Gökkuşağı alabalığı, balık beyni

Sublethal Doses of Inorganic Mercury Induce Dose-Depended Upregulation of RPA1 Content and Inhibit p53 Expression in the Brain of Rainbow Trout (Oncorhynchus mykiss)

Mercury (Hg) is one of most toxic and widespread element of aquatic environment. Almost every kind of the fish can accumulate Hg. Hg-induced peculiarities of cellular malfunction could be used as adequate biomarker to estimate the contamination risk in polluted aquatic ecosystems. The brain cells are high susceptible to the Hg compounds cytotoxicity. Various Hg species have different harmful effects on both structure and function of the brain cells. Neurotoxicity of inorganic Hg remains discussable and studied restrictedly. In this study, we have studied the role of RPA1 and p53 proteins in brain cell response to sublehtal (25% LD50 and 50% LD50) doses of inorganic Hg in rainbow trout (Oncorhynchus mykiss). LD50 value of Hg chloride in presented study was determined as 551 µg/L relate to 96 hours exposure. Two sublethal doses were used in the exposure rainbow trout at 2 and 7 days. The treatment with Hg chloride induced in fish brain dose-dependent increase in ROS level as well as time-dependent growth. Moreover, the exposure to both 25% and 50% LD50 Hg doses have caused significant upregulation of RPA1 expression. In the brain tissue of fish exposed to Hg for 2 days, it stimulated slightly expression of p53. Contrary, 7 days exposure induced significant decrease in p53 expression. The results of presented study evidence that sublethal doses of inorganic Hg are extremely neurotoxic and can induce in the fish brain signaling pathways disturbance through decline of stress sensor protein p53. Besides, the increase in RPA1 expression let to assume that brain cells of the fish can repair ROS-induced DNA breaks and prevent genotoxic effect of inorganic Hg. Overall, current data pointed out that inorganic mercury is high toxic to fish brain cells and this question requires future research.

Keywords:

Rainbow trout, fish brain,

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