TY - JOUR
T1 - Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells
AU - Jeong, Woo Sik
AU - Keum, Young Sam
AU - Chen, Chi
AU - Jain, Mohit R.
AU - Shen, Guoxiang
AU - Kim, Jung Hwan
AU - Li, Wenge
AU - Kong, Ah Ng Tony
PY - 2005
Y1 - 2005
N2 - Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE-reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.
AB - Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE-reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.
KW - ARE
KW - Chemopreventive agents
KW - HO-1
KW - Keap1
KW - Nrf2
UR - http://www.scopus.com/inward/record.url?scp=20444438012&partnerID=8YFLogxK
U2 - 10.5483/bmbrep.2005.38.2.167
DO - 10.5483/bmbrep.2005.38.2.167
M3 - Article
C2 - 15826493
AN - SCOPUS:20444438012
SN - 1225-8687
VL - 38
SP - 167
EP - 176
JO - Journal of Biochemistry and Molecular Biology
JF - Journal of Biochemistry and Molecular Biology
IS - 2
ER -