Leishmania spp.:: Delta-aminolevulinate-inducible neogenesis of porphyria by genetic complementation of incomplete heme biosynthesis pathway
Leishmania spp.:: Delta-aminolevulinate-inducible neogenesis of porphyria by genetic complementation of incomplete heme biosynthesis pathway
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DOI：
10.1016/j.exppara.2007.11.013
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发表时间：
2008-04-01
影响因子：
2.1
通讯作者：
Chang, Kwang-Poo
中科院分区：
文献类型：
--
作者：
Dutta, Sujoy;Furuyama, Kazumichi;Chang, Kwang-Poo
为了进一步发展卟啉病的利什曼原虫模型，基于它们在血红素生物合成中的缺陷，三个旧大陆物种如之前一样用编码途径中的第2和第3种酶的cDNAs双重转染亚马逊利什曼原虫。在蛋白质水平和功能上通过尿卟啉新生进行免疫学验证转基因的表达，所述尿卟啉新生仅在双转染子暴露于δ-氨基乙酰丙酸后发生。所有的物种检查同样缺乏血红素的生物合成，所示的积累尿卟啉作为唯一的卟啉和生产粪卟啉后，进一步转染的一个代表性的物种与下游基因。由此获得的结果表明，至少前五种血红素生物合成酶是不存在的所有物种检查，使他们的转染诱导与aminolevulinate积累卟啉，从而作为人类卟啉症的细胞模型是有用的。(c)2007爱思唯尔公司All rights reserved.
To further develop the Leishmania model for porphyria based on their deficiencies in heme biosynthesis, three Old World species were doubly transfected as before for Leishmania amazonensis with cDNAs, encoding the 2nd and 3rd enzymes in the pathway. Expression of the transgenes was verified immunologically at the protein level and functionally by uroporphyrin neogenesis that occurs only after exposure of the double-transfectants to delta-aminolevulinate. All species examined were equally deficient in heme biosynthesis, as indicated by the accumulation of uroporphyrin as the sole porphyrin and the production of coproporphyrin upon further transfection of one representative species with the downstream gene. The results obtained thus demonstrate that at least the first five enzymes for heme biosynthesis are absent in all species examined, rendering their transfectants inducible with aminolevulinate to accumulate porphyrins and thus useful as cellular models for human porphyrias. (c) 2007 Elsevier Inc. All rights reserved.