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Int. J. Mol. Sci. 2017, 18(5), 1089;

Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Faculty of Medicine and Life Sciences, BioMediTech, University of Tampere, 33014 Tampere, Finland
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland
School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland
SIBS Labs, University of Eastern Finland, 70211 Kuopio, Finland
Department of Ophthalmology, University of Tampere, SILK, TAUH Eye Center, Tampere University Hospital, 33014 Tampere, Finland
The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Department of Ophthalmology, Kuopio University Hospital, 70029 Kuopio, Finland
Author to whom correspondence should be addressed.
Academic Editors: Claudio Bucolo and Chiara Maria Eandi
Received: 17 January 2017 / Revised: 11 May 2017 / Accepted: 12 May 2017 / Published: 19 May 2017
(This article belongs to the Special Issue Retinal Diseases: Bridging Basic and Clinical Research)
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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. View Full-Text
Keywords: autophagy; macula; melanosome; proteasome; stem cell autophagy; macula; melanosome; proteasome; stem cell

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Juuti-Uusitalo, K.; Koskela, A.; Kivinen, N.; Viiri, J.; Hyttinen, J.M.T.; Reinisalo, M.; Koistinen, A.; Uusitalo, H.; Sinha, D.; Skottman, H.; Kaarniranta, K. Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells. Int. J. Mol. Sci. 2017, 18, 1089.

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