title: TAK1 is involved in the autophagy process in retinal pigment epithelial cells.
abstract: Autophagy is an evolutionarily conserved mechanism for degrading long-lived or malfunctioning proteins and organelles, such as those resulting from oxidative stress. Several publications have demonstrated the importance of the autophagy process in the pathophysiology of dry age-related macular degeneration (AMD). Still, the mechanism underlying this process and its involvement in dry AMD are not fully characterized. Investigating the autophagy process in retinal pigment epithelial (RPE) cells, we identified transforming growth factor β activated kinase 1 (TAK1) as a key player in the process. We found increased TAK1 phosphorylation in ARPE-19 and D407 cells treated with different inducers of autophagy, such as oxidative stress and rapamycin. Moreover, utilizing TAK1 specific inhibitor prior to oxidative stress or rapamycin treatment, we found significant reduction in LC3A/B-II expression. These results point at the involvement of TAK1 in the regulation of autophagy in RPE cells. This study suggests that aberrant activity of this kinase impairs autophagy and subsequently leads to alterations in the vitality of RPE cells. Proper activity of TAK1 may be essential for efficient autophagy, and crucial for the ability of RPE cells to respond to stress and dispose of damaged organelles, thus preventing or delaying retinal pathologies.
authors.affiliation: Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.|Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Yaron A
authors.initials: YA
authors.lastname: Green
authors.affiliation: Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.|Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Ben-Yaakov
authors.affiliation: Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.|Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Adir
authors.affiliation: Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.|Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Pollack
authors.affiliation: Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.|Kaplan Medical Center, Rehovot, affiliated with Hadassah-Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Dvashi
mesh_terms: D001343:Autophagy; D002478:Cells, Cultured; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D000099151:MAP Kinase Kinase Kinase 7
keywords: AMD; DMLA; ERP; LC3A/B-II; RPE; TAK1; autophagie; autophagy