Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 13, Issue 11, Pages 1639-1648Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2010.3226
Keywords
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Funding
- Innovative Drug Research Center [R11-2007-107-01002-0]
- National Research Foundation [R31-008-000-10103-0]
- National Research Foundation, the Ministry of Education, Science and Technology, Republic of Korea
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Induction of heme oxygenase-1 (HO-1) represents an important cellular adaptive survival response to oxidative stress and other toxic insults. In the present study, HepG2 cells grown in glucose-free media underwent apoptotic cell death, but they exhibited elevated expression of HO-1 before apoptosis manifested. Treatment of HepG2 cells with SnCl2, a HO-1 inducer, rescued these cells from glucose deprivation-induced apoptosis, while inhibition of the HO activity with zinc protoporphyrin IX exacerbated apoptosis under the same condition. HepG2 cells transfected with a dominant negative Nrf2 were more vulnerable to glucose deprivation-induced apoptosis compared to cells transfected with empty vector alone. To confirm the involvement of Nrf2 in the induction of HO-1 caused by glucose deprivation, we used embryonic fibroblasts prepared from nrf2(-/-), nrf2(+/-), and nrf2(+/+) embryos. Compared to the wild-type and the nrf2(+/-) embryonic fibroblasts, nrf2(-/-) cells were less prone to induce HO-1 expression upon glucose deprivation. Exposure of HepG2 cells to glucose-deprived media resulted in an elevated accumulation of reactive oxygen species (ROS). Pretreatment with N-acetylcysteine prevented the glucose deprivation-induced ROS accumulation and also the HO-1 expression. In conclusion, the Nrf2-mediated HO-1 upregulation upon glucose deprivation is mediated by ROS in HepG2 cells, and responsible for the adaptive survival response. Antioxid. Redox Signal. 13, 1639-1648.
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