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Nrf2-mediated heme oxygenase-1 upregulation as adaptive survival response to glucose deprivation-induced apoptosis in HepG2 cells

Cited 15 time in Web of Science Cited 17 time in Scopus
Authors
Lee, Hee Geum; Li, Mei-Hua; Joung, Eun-Joo; Na, Hye-Kyung; Cha, Young-Nam; Surh, Young-Joon
Issue Date
2010-12
Citation
Antioxidants and Redox Signaling, Vol.13 No.11, pp.1639-1648
Abstract
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.
ISSN
1523-0864
URI
https://hdl.handle.net/10371/172554
DOI
https://doi.org/10.1089/ars.2010.3226
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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