Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells
AbstractThe 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
- Supplementary File 1:
PDF-Document (PDF, 9687 KB)
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
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.
Juuti-Uusitalo K, Koskela A, Kivinen N, Viiri J, Hyttinen JMT, 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. International Journal of Molecular Sciences. 2017; 18(5):1089.Chicago/Turabian Style
Juuti-Uusitalo, Kati; Koskela, Ali; Kivinen, Niko; Viiri, Johanna; Hyttinen, Juha M.T.; Reinisalo, Mika; Koistinen, Arto; Uusitalo, Hannu; Sinha, Debasish; Skottman, Heli; Kaarniranta, Kai. 2017. "Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells." Int. J. Mol. Sci. 18, no. 5: 1089.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.