International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2010.631.637ChandruH. K.ChenG. 5201065Nitric oxide is known to regulate gene expression by modulating the activation of transcription factors. In organisms, it is synthesized from 1-arginine in the presence of an enzyme called nitric oxide synthase and it can act as a biosignaling molecule. Sulfotransferases (SULTs) are important phase II drug-metabolizing enzymes responsible for drug metabolism and xenobiotics detoxification. SULTs are also important in the regulation and metabolism of endogenous hormones and other important signaling molecules. This report investigates human SULT gene regulation by nitric oxide and the potential molecular mechanisms. Here we report the effect of nitric oxide on the expression of human SULT1A1 and SULT2A1, the two major human SULTs. When Hep G2 cells were treated with diethylene triamine/nitric oxide (DETA/NO), Western blot and q-RT-PCR data suggested that SULT2A1 was downregulated, while SULT1A1 was not significantly affected. The downregulation of SULT2A1 occurred in a time- and concentration-dependent manner. DETA/NO induced the phosphorylation of extracellular signal-regulated protein kinase (ERK). PD98059, a pharmacological inhibitor of ERK, prevented the DETA/NO downregulation of SULT2A1. The present study suggested that the downregulation of SULT2A1 involves ERK cell signaling pathways. This is the first report on nitrative stress regulation of human SULT2A1. The results are important for understanding biological functions of SULTs in organisms under stress.]]>Brune, B., A. Von Knethen and K.B. Sandau,19996969975Chen, G., D. Zhang, N. Jing, S. Yin, C.N. Falany and A. Radominska-Pandya,2003187186197Chen, X., S.M. Baker and G. Chen,200525354360Coughtrie, M.W., S. Sharp K. Maxwell and N.P. Innes,1998109327Dhakshinamoorthy, S. and A.G. Porter,20042792009620107Falany, C.N. and T.W. Wilborn,199427301329Gamage, N., A. Barnett, N. Hempel, R.G. Duggleby and K.F. Windmill et al.,200690522Glatt, H. and W. Meinl,20043695568Harris, R.M. and R.H. Waring,20089269275Hemish, J., N. Nakaya, V. Mittal and G. Enikolopov,20032784232142329Hengstler, J.G., M. Arand, M.E. Herrero and F. Oesch,19981544785Kimura, H., A. Weisz, Y. Kurashima, K. Hashimoto and T. Ogura et al.,200095189197Kohjitani, A., H. Fuda, O. Hanyu and C.A. Strott,20084307580Kroncke, K.D. and C. Carlberg,200014166173Lee, C.M., B.Y. Kim, L. Li and E.T. Morgan,2008283889898Lindsay, J., L.L. Wang, Y. Li and S.F. Zhou,2008999105Maiti, S. and G. Chen,2003418161168Maiti, S. and G. Chen,200331637644Maiti, S., X. Chen and G. Chen,2005964453Matthews, J.R., C.H. Botting, M. Panico, H.R. Morris and R.T. Hay,19962422362242Mokhtari, D., J.W. Myers and N. Welsh,200814930463053Nimmagadda, D., G. Cherala and S. Ghatta,200644171182Pilz, R.B., M. Suhasini, S. Idriss, J.L. Meinkoth and G.R. Boss,19959552558Runge-Morris, M. and T.A. Kocarek,20056299307Runge-Morris, M. and T.A. Kocarek,20092009728941728941Runge-Morris, M., K. Rose, C.N. Falany and T.A. Kocarek,199826795801Salinas, D., L. Sparkman, K. Berhane and V. Boggaram,2003285L1153L1165Seo, Y.K., Y.T. Chung, S. Kim, I. Echchgadda, C.S. Song and B. Chatterjee,2007386218223Sparkman, L. and V. Boggaram,2004287L764L773Wagner, E.F. and A.R. Nebreda,20099537549Yeh, C.T. and G.C. Yen,20062710081017Zaki, M.H., T. Akuta and T. Akaike,200598117129Yndestad, A., A.K. Marshall, J.D. Hodgkinson, L. Thamel, P.H. Sugden and A. Clerk,201042263272Obara, Y. and N. Nakahata,2010771016