Sugatani Junko, Sueyoshi Tatsuya, Negishi Masahiko, Miwa Masao
Department of Pharmaco-Biochemistry and 21 COE, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Methods Enzymol. 2005;400:92-104. doi: 10.1016/S0076-6879(05)00006-6.
Human UDP-glucuronosyltransferase (UGT) 1A1 is the enzyme that detoxifies neurotoxic bilirubin by conjugating it with glucuronic acid. In addition to bilirubin, UGT1A1 conjugates various endogenous and exogenous lipophilic compounds such as estrogens and the active metabolite of the anticancer drug irinotecan SN-38. Thus, activation by specific inducers of the UGT1A1 gene is critical in treating patients with unconjugated hyperbili-rubinemia and in preventing side effects of drug treatment such as SN-38-induced toxicity. This chapter describes the experimental processes used to identify the 290-bp distal enhancer module at -3499/-3210 of the UGT1A1 gene and to characterize its regulation by nuclear receptors: constitutive active/androstane receptor, pregnane X receptor, and glucocorticoid receptor.
人尿苷二磷酸葡萄糖醛酸转移酶（UGT）1A1是一种通过将神经毒性胆红素与葡萄糖醛酸结合来使其解毒的酶。除胆红素外，UGT1A1还能结合多种内源性和外源性亲脂性化合物，如雌激素和抗癌药物伊立替康的活性代谢产物SN-38。因此，UGT1A1基因的特异性诱导剂激活对于治疗非结合型高胆红素血症患者以及预防药物治疗的副作用（如SN-38诱导的毒性）至关重要。本章描述了用于鉴定UGT1A1基因-3499/-3210处290 bp远端增强子模块并表征其受核受体（组成型活性/雄甾烷受体、孕烷X受体和糖皮质激素受体）调控的实验过程。
