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

Year 2019, , 462 - 476, 23.07.2019

Mehmet Reşit Taysı , Bünyamin Söğüt Victor S. Nedzvetsky Muammer Kırıcı Can Ali Ağca

https://doi.org/10.30910/turkjans.595352

Abstract

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

Thanks

This study was produced from the doctoral thesis prepared by the first author consultation with the second author.

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

Abstract

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.

Keywords

Gökkuşağı alabalığı, balık beyni

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