Characterization of stress response in human retinal epithelial cells.

Characterization of stress response in human retinal epithelial cells.
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DOI:
10.1111/j.1582-4934.2012.01652.x
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发表时间:
2013-01
影响因子:
5.3
通讯作者:
Torriglia A
Torriglia A
中科院分区:
医学2区
文献类型:
--
作者:
Giansanti V;Rodriguez GE;Savoldelli M;Gioia R;Forlino A;Mazzini G;Pennati M;Zaffaroni N;Scovassi AI;Torriglia A

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年龄相关性黄斑变性(AMD)的发病机制涉及视网膜色素上皮细胞的死亡和光感受器的死亡。在这篇文章中,我们研究了成人视网膜色素上皮细胞(ARPE-19)对5-(N,N-氨基)阿米洛利(HMA),一种Na+/H+交换抑制剂的反应。我们观察到用HMA处理的ARPE-19细胞不能激活“经典”凋亡,但它们成功地激活自噬。在HMA暴露的前2小时,自噬在保护细胞免于死亡方面是有效的。此后,自噬受损,如p62积累所示,这种保护机制成为细胞死亡的刽子手。这种自噬特性的转换作为单一刺激的时间函数在这里首次显示。在较小程度上,观察到自噬的激活,与依托泊苷,这表明该事件可能是ARPE细胞的一般反应,压力和最重要的途径参与细胞抵抗不利条件和毒性刺激。
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.
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