{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:40:06Z","timestamp":1781721606464,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:00:00Z","timestamp":1495152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Research Council of the Academy of Finland","award":["139567"],"award-info":[{"award-number":["139567"]}]},{"name":"Health Research Council of the Academy of Finland","award":["218050"],"award-info":[{"award-number":["218050"]}]},{"name":"Health Research Council of the Academy of Finland","award":["137801"],"award-info":[{"award-number":["137801"]}]},{"name":"the VTR grants of Kuopio University Hospital"},{"name":"the Finnish Eye Foundation"},{"name":"the Finnish Funding Agency for Technology and Innovation"},{"name":"the P\u00e4ivikki and Sakari Sohlberg Foundation"},{"DOI":"10.13039\/501100013510","name":"Eye and Tissue Bank Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011905","name":"Evald and Hilda Nissi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011905","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Finnish Cultural Foundation - North-Savo"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms18051089","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T01:47:33Z","timestamp":1495504053000},"page":"1089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Kati","family":"Juuti-Uusitalo","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Life Sciences, BioMediTech, University of Tampere, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Koskela","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niko","family":"Kivinen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Viiri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Hyttinen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Reinisalo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arto","family":"Koistinen","sequence":"additional","affiliation":[{"name":"SIBS Labs, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"Uusitalo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tampere, SILK, TAUH Eye Center, Tampere University Hospital, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasish","family":"Sinha","sequence":"additional","affiliation":[{"name":"The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Skottman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, BioMediTech, University of Tampere, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland"},{"name":"Department of Ophthalmology, Kuopio University Hospital, 70029 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. 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