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PGC-1α Regulates the Interplay Between Oxidative Stress, Senescence and Autophagy in the Ageing Retina Important in Age-related Macular Degeneration

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Journal J Cell Mol Med
Date 2024 Apr 4
PMID 38571282
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Abstract

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1α protein, and nuclear factor erythroid 2 like 2 (NFE2L2) gene, exhibited some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1α in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defence, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defence also contributed to that discrimination. A bioinformatic analysis showed that PGC-1α might coordinate the interplay between genes encoding proteins involved in antioxidant defence, senescence and autophagy in the ageing retina. These data support importance of PGC-1α in AMD pathogenesis and confirm the utility of mice with PGC-1α knockout as an animal model to study AMD pathogenesis.

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References
1.
Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier C . PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010; 189(2):211-21. PMC: 2856912. DOI: 10.1083/jcb.200910140. View

2.
Golestaneh N, Chu Y, Cheng S, Cao H, Poliakov E, Berinstein D . Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration. J Transl Med. 2016; 14(1):344. PMC: 5175395. DOI: 10.1186/s12967-016-1101-8. View

3.
Popov D, Lysenko E, Kuzmin I, Vinogradova V, Grigoriev A . Regulation of PGC-1α Isoform Expression in Skeletal Muscles. Acta Naturae. 2015; 7(1):48-59. PMC: 4410395. View

4.
Lim L, Mitchell P, Seddon J, Holz F, Wong T . Age-related macular degeneration. Lancet. 2012; 379(9827):1728-38. DOI: 10.1016/S0140-6736(12)60282-7. View

5.
Budanov A . The role of tumor suppressor p53 in the antioxidant defense and metabolism. Subcell Biochem. 2014; 85:337-58. PMC: 4206257. DOI: 10.1007/978-94-017-9211-0_18. View