Characterization of stress response in human retinal epithelial cells

Journal of Cellular and Molecular Medicine

Vincenzo Giansanti⁴  Gloria E. Villalpando Rodriguez²  Michelle Savoldelli⁵  Roberta Gioia³  Antonella Forlino³  Giuliano Mazzini⁴  Marzia Pennati¹  Nadia Zaffaroni¹  Anna Ivana Scovassi⁴ 

[1] Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;U872 eq. 17, Centre de Recherches des Cordeliers, INSERM, Paris, France;Dipartimento di Biochimica, Università di Pavia, Pavia, Italy;Istituto di Genetica Molecolare, CNR, Pavia, Italy;Departement Ophtalmologie, Hotel Dieu, Paris, France

关键词: Apoptosis;    ARPE‐19 cells;    autophagy;    caspases;    HMA;    L‐DNase II;    PARP‐1;   

DOI  :  10.1111/j.1582-4934.2012.01652.x

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.