Lee Hyung Il, Jang So-Young, Kang Hyun Tae, Hwang Eun Seong
Department of Life Science, University of Seoul, Dongdaemungu, Jeonnongdong 90, Seoul 130-743, Republic of Korea.
Biochem Biophys Res Commun. 2008 Apr 4;368(2):298-304. doi: 10.1016/j.bbrc.2008.01.082. Epub 2008 Jan 28.
Nicotinamide at mM concentration is a potent inhibitor of certain key molecules involved in cell survival, such as SIRT1 and PARP-1, and affects cell survival in various conditions in vivo and in vitro. However, the effect of an acute treatment of nicotinamide on gene expression has rarely been closely examined. In our study, the treatment of 10mM nicotinamide downregulated p21WAF1 expression in various human cells including p53-negative or SIRT1-knockdown cells indicating gene regulation not mediated by p53 or SIRT1. Meanwhile, in the nicotinamide-treated cells, Sp1 activity and protein level was substantially reduced due to increased proteasome-mediated degradation. Our results indicate that nicotinamide treatment attenuates p21WAF1 expression through Sp1 downregulation, and suggest a possible involvement of nicotinamide metabolism in cellular gene expression.
毫摩尔浓度的烟酰胺是参与细胞存活的某些关键分子（如SIRT1和PARP - 1）的有效抑制剂，并在体内和体外的各种条件下影响细胞存活。然而，烟酰胺急性处理对基因表达的影响很少得到仔细研究。在我们的研究中，10毫摩尔烟酰胺处理下调了包括p53阴性或SIRT1敲低细胞在内的各种人类细胞中的p21WAF1表达，表明基因调控不是由p53或SIRT1介导的。同时，在烟酰胺处理的细胞中，由于蛋白酶体介导的降解增加，Sp1活性和蛋白质水平大幅降低。我们的结果表明，烟酰胺处理通过下调Sp1减弱p21WAF1表达，并提示烟酰胺代谢可能参与细胞基因表达。
