Synergy between sulforaphane and selenium in the up-regulation of thioredoxin reductase and protection against hydrogen peroxide-induced cell death in human hepatocytes

详细信息	查看全文 | 推荐本文 |

• 作者：Dan Li^a ; ¹ ; Wei Wang^b ; Yujuan Shan^a ; Lawrence N. Barrera^b ; Alexander F. Howie^c ; Geoffrey J. Beckett^c ; Kun Wu^a ; ^{wukun_15000@126.com} ; Yongping Bao^b ; ^{y.bao@uea.ac.uk}
• 关键词：Cruciferous vegetable ; Sulforaphane ; Selenium ; Thioredoxin reductase ; Dietary supplement ; Hepatocytes
• 刊名：Food Chemistry
• 出版年：2012
• 期刊代码：48_03088146
• 类别：abs
• 出版时间：15 July, 2012
• 卷：133
• 期：2
• 页码：300-307
• 文件大小：596 K

摘要

Dietary isothiocyanates and selenium are chemopreventive agents and potent inducers of antioxidant enzymes. It has been previously shown that sulforaphane and selenium have a synergistic effect on the upregulation of thioredoxin reductase-1 (TrxR-1) in human hepatoma HepG2 cells. In this paper, further evidence is presented to show that sulforaphane and selenium synergistically induce TrxR-1 expression in immortalised human hepatocytes. Sulforaphane was found to be more toxic toward hepatocytes than HepG2 cells with IC₅₀ = 25.1 and 56.4 渭M, respectively. Sulforaphane can protect against hydrogen peroxide-induced cell death and this protection was enhanced by co-treatment with selenium. Using siRNA to knock down TrxR-1 or Nrf2, sulforaphane (5 渭M)-protected cell viability was reduced from 73%to 46%and 34%, respectively, suggesting that TrxR-1 is an important enzyme in protection against hydrogen peroxide-induced cell death. Sulforaphane-induced TrxR-1 expression was positively associated with significant levels of Nrf2 translocation into the nucleus, but co-treatment with selenium showed no significant increase in Nrf2 translocation. Moreover, MAPK (ERK, JNK and p38) and PI3K/Akt signalling pathways were found to play no significant role in sulforaphane-induced Nrf2 translocation into the nucleus. However, blocking ERK and JNK signalling pathways decreased sulforaphane-induced TrxR-1 mRNA by about 20%; whereas blocking p38 and PI3K/AKT increased TrxR-1 transcription. In summary, a combination of sulforaphane and selenium resulted in a synergistic upregulation of TrxR-1 that contributed to the enhanced protection against free radical-mediated oxidative damage in human hepatocytes.