Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/ijms18051089
Keywords
autophagy; macula; melanosome; proteasome; stem cell
Funding
- Kuopio University Hospital [5503743]
- Finnish Eye Foundation
- Finnish Funding Agency for Technology and Innovation
- Health Research Council of the Academy of Finland [139567, 218050, 137801]
- Paivikki and Sakari Sohlberg Foundation
- Eye and Tissue Bank Foundation
- Evald and Hilda Nissi Foundation
- Finnish Cultural Foundation-North-Savo
- Academy of Finland (AKA) [139567, 139567] Funding Source: Academy of Finland (AKA)
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The impairment of autophagic and proteasomal cleansing together with changes in pigmentation has been documented in retinal pigment epithelial (RPE) cell degeneration. However, the function and co-operation of these mechanisms in melanosome-containing RPE cells is still unclear. We show that inhibition of proteasomal degradation with MG-132 or autophagy with bafilomycin A1 increased the accumulation of premelanosomes and autophagic structures in human embryonic stem cell (hESC)-derived RPE cells. Consequently, upregulation of the autophagy marker p62 (also known as sequestosome-1, SQSTM1) was confirmed in Western blot and perinuclear staining. Interestingly, cells treated with the adenosine monophosphatedependent protein kinase activator, AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), decreased the proteasome inhibitor-induced accumulation of premelanosomes, increased the amount of autophagosomes and eradicated the protein expression of p62 and LC3 (microtubule-associated protein 1A/1B-light chain 3). These results revealed that autophagic machinery is functional in hESC-RPE cells and may regulate cellular pigmentation with proteasomes.
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