缺氧(环境)
胆绿素还原酶
胆绿素
细胞生物学
生物
活性氧
细胞内
下调和上调
癌症研究
血红素
化学
生物化学
酶
血红素加氧酶
基因
氧气
有机化学
作者
Sung Su Kim,Sin Seong,Seong Hyeon Lim,Sung Young Kim
标识
DOI:10.1016/j.bbrc.2013.09.120
摘要
Hypoxia-induced alterations in the cellular redox status play a critical role in the development of hypoxia-induced chemoresistance in cancer cells. Human biliverdin reductase (hBVR), an enzyme involved in the conversion of biliverdin into bilirubin in heme metabolism, was recently identified as an important cytoprotectant against oxidative stress and hypoxia. However, the role of hBVR on hypoxia-induced drug resistance has not been previously investigated. Using human glioblastoma cell lines, we evaluated the potential role of hBVR in hypoxia-induced drug resistance. We found that hypoxia caused a significant increase in hBVR expression in glioblastoma cells that was accompanied by chemoresistance. We also observed that siRNA-based targeting of hBVR genes attenuated the hypoxia-induced chemoresistance. Furthermore, knocking down hBVR induced a marked increase in the levels of intracellular reactive oxygen species under hypoxic conditions, and the chemosensitizing effect of hBVR depletion was reversed by pretreatment with the antioxidant N-acetylcysteine. These findings suggest that hBVR significantly contributes to the modulation of hypoxia-induced chemoresistance of glioblastoma cells by adjusting their cellular redox status.
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