Isolation of multiple normal and functionally defective forms of uridine diphosphate-glucuronosyltransferase from inbred Gunn rats.
Isolation of multiple normal and functionally defective forms of uridine diphosphate-glucuronosyltransferase from inbred Gunn rats.
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从近交 Gunn 大鼠中分离多种正常和功能缺陷形式的尿苷二磷酸-葡萄糖醛酸基转移酶。
DOI：
10.1172/jci112816
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
RoyChowdhury,J
中科院分区：
文献类型：
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作者：
RoyChowdhury,N;Gross,F;Moscioni,AD;Kram,M;Arias,IM;RoyChowdhury,J
Gunn 大鼠是 Wistar 大鼠的突变品系，由于缺乏针对胆红素的肝尿苷二磷酸-葡萄糖醛酸基转移酶（UDPGT；EC.2.4.1.17）活性，因此患有非结合高胆红素血症。我们从近交 Wistar (RHA) 大鼠和同源 Gunn 大鼠肝脏的可溶微粒体组分中分离出 5 种 UDPGT 亚型。 Wistar (RHA) 大鼠的 UDPGT 同工型 V（洗脱 pH 7.5）对胆红素和 4'-羟基二甲基氨基偶氮苯具有活性。来自 Gunn 大鼠肝脏的相应亚型没有酶活性，但在 NaDodSO4/聚丙烯酰胺凝胶电泳 (Mr 53,000) 上表现出正常的洗脱 pH 值和迁移率，并被 UDPGT 特异性抗血清识别。 Wistar (RHA) 和 Gunn 大鼠的 UDPGT 同种型 I（洗脱 pH 8.7）对 4-硝基苯酚有活性。来自 Gunn 大鼠肝脏的亚型仅具有正常 UDPGT 活性的 10%，但是在体外添加 15 mM 二乙基亚硝胺后，UDPGT 活性增加至正常。 Gunn 大鼠的亚型 II（洗脱 pH 8.4）、III（洗脱 pH 8.0）和 IV（洗脱 pH 7.8）具有正常的 UDPGT 活性，但亚型 IV 对胆红素无活性。
Gunn rats are a mutant strain of Wistar rats that have unconjugated hyperbilirubinemia due to absence of hepatic uridine diphosphate-glucuronosyltransferase (UDPGT; EC. 2.4.1.17) activity toward bilirubin. We isolated five UDPGT isoforms from solubilized microsomal fractions from liver of inbred Wistar (RHA) rats and congeneic Gunn rats. UDPGT isoform V (elution pH 7.5) from Wistar (RHA) rats is active toward bilirubin and 4'-hydroxydimethylaminoazobenzene. The corresponding isoform from Gunn rat liver was enzymically inactive but exhibited normal elution pH and mobility on NaDodSO4/polyacrylamide gel electrophoresis (Mr 53,000), and was recognized by a UDPGT-specific antiserum. UDPGT isoform I (elution pH 8.7) from Wistar (RHA) and Gunn rats was active toward 4-nitrophenol. The isoform from Gunn rat liver had only 10% of normal UDPGT activity, however UDPGT activity increased to normal upon addition of 15 mM diethylnitrosamine in vitro. Isoforms II (elution pH 8.4), III (elution pH 8.0), and IV (elution pH 7.8) from Gunn rats had normal UDPGT activities, except that Isoform IV was inactive toward bilirubin.Images