TY - JOUR
T1 - Copper mediates mitochondrial biogenesis in retinal pigment epithelial cells
AU - Aloysius Dhivya, M.
AU - Aberami, S.
AU - Nikhalashree, Sampath
AU - Biswas, J.
AU - Liu, Wenjie
AU - Irudayaraj, Joseph
AU - Sulochana, K. N.
AU - Coral, Karunakaran
AU - Bharathi Devi, S. R.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - AMD
KW - Copper
KW - Mitochondrial biogenesis
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U2 - 10.1016/j.bbadis.2020.165843
DO - 10.1016/j.bbadis.2020.165843
M3 - Article
C2 - 32454166
AN - SCOPUS:85085741878
SN - 0925-4439
VL - 1866
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 10
M1 - 165843
ER -