Reduction of arsenic-induced cytotoxicity through Nrf2/HO-1 signaling in HepG2 cells
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概要
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Our previous study indicated that Nrf2 is a key transcription factor in cellular defenses against inorganic arsenite (iAsIII). However, the role of heme oxygenase-1 (HO-1), which is regulated by Nrf2, in iAsIII-induced cytotoxicity is poorly understood. To address this issue, we examined the contribution of HO-1 to iAsIII-mediated Nrf2 activation and in protection against iAsIII cytotoxicity in HepG2 cells. Exposure of HepG2 cells to iAsIII (10 µM) caused persistent induction of HO-1 accompanied by prolonged Nrf2 activation, whereas siRNA-mediated knockdown of HO-1 decreased prolonged Nrf2 activation. Pretreatment with either HO-1 siRNA or HO inhibitor (tin protoporphyrin IX) significantly enhanced iAsIII-induced cytotoxicity. These results suggest that iAsIII-induced HO-1 appears, at least in part, to act as a positive feedback regulator of Nrf2 activation, thereby diminishing its cytotoxicity in HepG2 cells.
- 2010-06-01
著者
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Sumi Daigo
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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Sumi Daigo
Master's Program In Environmental Sciences University Of Tsukuba:doctoral Programs In Medical S
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Shinkai Yasuhiro
Doctoral Program In Life System Medical Sciences Graduate School Of Comprehensive Human Sciences Uni
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Shinkai Yasuhiro
Organization For Frontier Research In Preventive Pharmaceutical Sciences Hokuriku University
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Kumagai Yoshito
Doctoral Program In Life System Medical Sciences Graduate School Of Comprehensive Human Sciences Uni
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Kumagai Yoshito
Doctoral Program In Life System Medical Sciences Graduate School Of Comprehensive Human Sciences
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Kumagai Yoshito
Master's Program In Environmental Sciences University Of Tsukuba:doctoral Programs In Medical S
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ABIKO Yumi
Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, U
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Abiko Yumi
Doctoral Program In Life System Medical Sciences Graduate School Of Comprehensive Human Sciences Uni
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Kumagai Yoshito
Doctoral Program In Biomedical Sciences Graduate School Of Comprehensive Human Sciences University Of Tsukuba
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Shinkai Yasuhiro
Doctoral Program In Biomedical Sciences Graduate School Of Comprehensive Human Sciences University Of Tsukuba
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