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Copper mediates mitochondrial biogenesis in retinal pigment epithelial cells.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 6.2 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.bbadis.2020.165843
M Aloysius Dhivya 1 , S Aberami 2 , Sampath Nikhalashree 1 , J Biswas 3 , Wenjie Liu 4 , Joseph Irudayaraj 4 , K N Sulochana 2 , Karunakaran Coral 2 , S R Bharathi Devi 2
Affiliation  

Age related macular degeneration (AMD) is a multifactorial disease with genetic, biochemical and environmental risk factors. We observed a significant increase in copper levels in choroid-RPE from donor eyeballs with AMD. Adult retinal pigment epithelial cells (ARPE19 cells) exposed to copper in-vitro showed a 2-fold increase in copper influx transporter CTR1 and copper uptake at 50 μM concentration. Further there was 2-fold increase in cytochrome C oxidase activity and a 2-fold increase in the mRNA expression of NRF 2 with copper treatment. There was a significant increase in mitochondrial biogenesis markers PGC1β and TFAM which was confirmed by mitochondrial mass and copy number. On the contrary, in AMD choroid-RPE, the CTR1 mRNA was found to be significantly down-regulated compared to its respective controls. SCO1 and PGC1β mRNA showed an increase in choroid–RPE. Our study proposes copper to play an important role in mitochondrial biogenesis in RPE cells.



中文翻译:

铜介导视网膜色素上皮细胞中线粒体的生物发生。

年龄相关性黄斑变性(AMD)是一种多因素疾病,具有遗传,生化和环境危险因素。我们观察到AMD供体眼球的脉络膜RPE中铜水平显着增加。体外暴露于铜的成年视网膜色素上皮细胞(ARPE19细胞)在50μM浓度下铜内流转运蛋白CTR1和铜吸收量增加了2倍。另外,用铜处理后,细胞色素C氧化酶活性增加了2倍,而NRF 2的mRNA表达增加了2倍。线粒体生物发生标记PGC1β和TFAM显着增加,这由线粒体质量和拷贝数证实。相反,在AMD脉络膜RPE中,与相应的对照相比,CTR1 mRNA被显着下调。SCO1和PGC1βmRNA显示脉络膜RPE增加。我们的研究表明铜在RPE细胞的线粒体生物发生中起重要作用。

更新日期:2020-05-23
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