Çevresel Kirleticiler ve Plasental Transporterlar: PCB ile SLC ve ABCB1 Örneği

Year 2022, , 29 - 37, 01.12.2022

Begüm Yurdakök Dikmen , Recep Uyar , Özgür Kuzukıran , Mehmet Altay Ünal , Tolga Çelik , Ümmü Gülsüm Boztepe , Kübra Karakaş Alkan , Özgür Özyünü , Yağmur Turgut , Hilal Özdağ Sevgili , Halit Kanca , Çağdaş Aktan , Ayhan Filazi

https://doi.org/10.53424/balikesirsbd.1159774

Abstract

Amaç: Çevresel kirletici maruziyetine bağlı olarak işlevselliği değişen ve bozulan membran transportları nedeniyle, bu maddeler plasental bariyeri geçerek plasental kan dolaşımına geçebilmektedir. Çalışmada, çevresel kirleticilerin bu transport proteinleriyle etkileşimlerinin moleküler boyutta incelenmesi amaçlanmaktadır. Gereç ve Yöntem: Araştırma kapsamında hemokoryal yapıya sahip insan ve endotelyokoryal yapıya sahip köpek plasentasında; 28 kirleticinin analizi GC-MS ile yapılmış (PCB, PBDE, PAH ve Organik klorlu pestisitler); RNAseq ile plasental tüm genom ifade profili araştırılmış, in siliko (moleküler kenetleme) ve in vitro (PCB 101, PCB118 uygulanan plasental hücre hattı HTR8/SVneo’da SLC ve ABCB1 mRNA ifadesi) değerlendirilmiştir. Bulgular: Test edilen 60 örnek içerisinde bir örnekte PCB101 826.4μg/kg; 23 örnekte ise PCB118 0.14 ile 41,9μg/kg arasında bulundu. Biyoinformatik bulgularda sekans analizi yapılan 55 numunede PCB pozitif ve negatif numuneler arasında 742 gende farklılık bulundu (p<0.05). Bu genler içerisinde 14 adet SLC ve 2adet ABC ailesinde gruplara göre ifade farklılığı bulundu. SLC içerisinde en düşük p değerine sahip ilk iki gen SLC4A1 (p=0.000126) ve SLC38A5 (p=0.000563) olurken, ABC’ler içerisinde ABCA8 (0.022997) ve ABCC1 (p=0.025288) olarak bulundu. qPCR bulgularına göre hem ABCB1 için hem de SLC22A6 için mRNA ifadesinde artış görülmekte birlikte bu artış ABCB1 için daha yüksek bulundu (p<0.05). Sonuç: ABCB1 gen ifadesi ve PCB ligandlarına bağlanma affiniteleri de SLC (SLC1A5)’ye göre daha yüksek bulundu. Sonuç olarak PCB maruziyetinin ABCB1 ifadesini değerlendirmeye alınan SLC’lere göre daha fazla etkilediği gösterildi.

Keywords

Plasenta, genomik, PCB, SLC, ABCB1

Supporting Institution

TÜBİTAK

Project Number

119S702

Environmental Contaminants and Placental Transporters: Example of PCB vs. SLC and ABCB1

Abstract

Objective: Due to widespread presence and exposure to environmental pollutants, structural and functional changes in membrane transporters could occur, leading to plasental transport of these compounds. In this study, the effects of PCBs on SLC abd ABCB1 membrane transport molecules were evaluated. Materials and Methods: Hemochorial structured human placenta and endotheliochorial structured dog placenta were analyzed for 28 pollutants (PCB, PBDE, PAH and Organochlorines) using GC-MS. The expression profile of the placental whole genome were investigated with RNAseq, and in silico (molecular chelation) and in vitro (SLC and ABCB1 mRNA expression in the placental cell line HTR8/SVneo treated with PCB 101, PCB118) were evaluated. Results: PCB101 826.4μg/kg in one sample out of 60 samples tested; In 23 samples, PCB118 was found to be between 0.14 and 41.9μg/kg. In the bioinformatics findings, there were differences in 742 genes between PCB positive and negative samples in 55 samples that were sequenced (p<0.05). Among these genes, expression differences were found in 14 SLC and 2 ABC families according to groups. The first two genes with the lowest p values in SLC were SLC4A1 (p=0.000126) and SLC38A5 (p=0.000563), while ABCA8 (p=0.022997) and ABCC1 (p=0.025288) were found in ABCs. According to the qPCR findings, there was an increase in mRNA expression for both ABCB1 and SLC22A6, but this increase was found to be higher for ABCB1 (p<0.05). Conclusion: ABCB1 gene expression and binding affinities to PCB ligands were also higher than SLC (SLC1A5). Placental PCB exposure affected ABCB1 expression more than the tested SLCs.

Keywords

Placenta, genomic, PCB, SLC, ABCB1

Project Number

119S702

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