title: Characterization of stress response in human retinal epithelial cells.
abstract: The pathogenesis of age-related macular degeneration (AMD) involves demise of the retinal pigment epithelium and death of photoreceptors. In this article, we investigated the response of human adult retinal pigmented epithelial (ARPE-19) cells to 5-(N,N-hexamethylene)amiloride (HMA), an inhibitor of Na(+) /H(+) exchangers. We observed that ARPE-19 cells treated with HMA are unable to activate 'classical' apoptosis but they succeed to activate autophagy. In the first 2 hrs of HMA exposure, autophagy is efficient in protecting cells from death. Thereafter, autophagy is impaired, as indicated by p62 accumulation, and this protective mechanism becomes the executioner of cell death. This switch in autophagy property as a function of time for a single stimulus is here shown for the first time. The activation of autophagy was observed, at a lesser extent, with etoposide, suggesting that this event might be a general response of ARPE cells to stress and the most important pathway involved in cell resistance to adverse conditions and toxic stimuli.
authors.affiliation: Istituto di Genetica Molecolare, CNR, Pavia, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Giansanti
authors.forename: Gloria E Villalpando
authors.initials: GE
authors.lastname: Rodriguez
authors.forename: Michelle
authors.initials: M
authors.lastname: Savoldelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Gioia
authors.forename: Antonella
authors.initials: A
authors.lastname: Forlino
authors.forename: Giuliano
authors.initials: G
authors.lastname: Mazzini
authors.forename: Marzia
authors.initials: M
authors.lastname: Pennati
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: Anna Ivana
authors.initials: AI
authors.lastname: Scovassi
authors.forename: Alicia
authors.initials: A
authors.lastname: Torriglia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D001693:Biological Transport, Active; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D059003:Topoisomerase Inhibitors / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017382:Reactive Oxygen Species; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D017923:Sodium-Hydrogen Exchangers; D059003:Topoisomerase Inhibitors; C057360:5-(N,N-hexamethylene)amiloride; D005047:Etoposide; D000584:Amiloride; D020169:Caspases