Bcl-2 sustains hormetic response by inducing Nrf-2 nuclear translocation in L929 mouse fibroblasts

• Published in: Free radical biology & medicine Vol. 49; no. 7; pp. 1192 - 1204
• Main Authors: Luna-López, Armando, Triana-Martínez, Francisco, López-Diazguerrero, Norma E., Ventura-Gallegos, José L., Gutiérrez-Ruiz, María C., Damián-Matsumura, Pablo, Zentella, Alejandro, Gómez-Quiroz, Luis E., Königsberg, Mina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-10-2010
• Subjects: Active Transport, Cell Nucleus - drug effects; Active Transport, Cell Nucleus - genetics; Animals; Bcl-2; Benzopyrans - pharmacology; Cell Line; Cell Nucleus - metabolism; Cytoprotection - drug effects; Cytoprotection - genetics; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Free radicals; GST; Hormesis; Hydrogen Peroxide - pharmacology; Mice; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nitriles - pharmacology; Nrf-2; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; RNA, Small Interfering - genetics; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; γGCS; Bcl-2; Oxidative stress; Free radicals; ARE; OCH; Nrf-2; ROS; GST; Hormesis; γGCS; GSH
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2010.07.004

Hormesis is the process whereby exposure to a low dose of a chemical agent induces an adaptive effect on the cell or organism. This response evokes the expression of cytoprotective and antioxidant proteins, allowing pro-oxidants to emerge as important hormetic agents. The antiapoptotic protein Bcl-2 is known to protect cells against death induced by oxidants; it has been suggested that Bcl-2 might also modulate steady-state reactive oxygen species levels. The aim of this work was to find out if Bcl-2 might play a role during the hormetic response and in Nrf-2 activation. We have established a model to study the oxidative conditioning hormesis response (OCH) by conditioning the cell line L929 with 50
μM H
2O
2 for 9
h. This condition did not induce oxidative damage nor oxidative imbalance, and OCH cells maintained a 70–80% survival rate after severe H
2O
2 treatment compared to nonconditioned cells. When cells were pretreated with the Bcl-2 inhibitor HA14-1 or were silenced with Bcl-2-siRNA, both the hormetic effect and the Nrf-2 nuclear translocation previously observed were abrogated. Our results suggest a sequence of causal events related to increase in Bcl-2 expression, induction of Nrf-2 activation, and sustained expression of cytoprotective proteins such as GST and γGCS.