PDTC inhibits NF-□B activation by inhibiting proteasome activity through the mediation of zinc
作者单位：Brain Korea 21 Project for Medical Sciences Brain Research Institute and Department of Pharmacology Yonsei University College of Medicine Seoul 120-752 Korea
会议名称：《中国药理学会第八次全国代表大会暨全国药理学术会议》
会议日期：2002年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
摘 要：Pyrrolidine dithiocarbamate (PDTC) is a potent inhibitor of nuclear factor kappa B (NF-□B). Wehave previously reported that the effects of pyrrolidine dithiocarbamate(PDTC) on cell death andNF-□B inhibition are zinc dependent(Kim et al, FEBS Lett. 449, 28-32, 1999, Kim, et al, ***. 72, 1586-1592, 1999), not through its antioxidant effect. In the present study, wesought to characterize the molecular mechanism of PDTC inhibition of NF-□B activity. PDTC didnot alter NF-□B binding to DNA, bat prevented the translocation of the p65 subunit of NF-□Binto the nucleus. As an inhibitor of NF-□B, PDTC paradoxically activated I□B kinase (IKK).But, degradation of phosphorylated I□B□was blocked by PDTC. PDTC also stabilized andincreased p53 and p21 proteins that are degraded by proteasome. A highly specific proteasome