Autophagy regulates proteasome inhibitor-induced pigmentation in human embryonic stem cell-derived retinal pigment epithelial cells

Kati Juuti-Uusitalo, Ali Koskela, Niko Kivinen, Johanna Viiri, Juha M.T. Hyttinen, Mika Reinisalo, Arto Koistinen, Hannu Uusitalo, Debasish Sinha, Heli Skottman, Kai Kaarniranta

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number1089
JournalInternational journal of molecular sciences
Volume18
Issue number5
DOIs
StatePublished - May 19 2017

Keywords

  • Autophagy
  • Macula
  • Melanosome
  • Proteasome
  • Stem cell

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'Autophagy regulates proteasome inhibitor-induced pigmentation in human embryonic stem cell-derived retinal pigment epithelial cells'. Together they form a unique fingerprint.

Cite this