A Drosophila systems approach to xenobiotic metabolism.

A Drosophila systems approach to xenobiotic metabolism.
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果蝇系统的外源代谢方法。

DOI:
10.1152/physiolgenomics.00018.2007
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发表时间:
2007
影响因子:
4.6
通讯作者:
Yang J
Yang J
中科院分区:
生物学3区
文献类型:
--
作者:
Yang J

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杀虫剂耐药性是医药和农业的一个主要问题,经常与代谢酶的过度表达有关,这些代谢酶催化农药的分解,导致广谱耐药性。然而,这些代谢酶通常驻留在昆虫组织中的情况仍不清楚。对果蝇9个成体组织的微阵列分析表明,细胞色素P-450和谷胱甘肽-S转移酶具有高度的组织特异性表达模式;大多数局限于一个或多个上皮组织,一半在单个组织中显性表达。因此,外来物所遇到的特定解毒酶严重依赖于给药途径。特别是,已知的杀虫剂代谢基因在昆虫的马氏(肾)小管中高度丰富,这意味着它们参与了异种代谢。因此,在脂肪体中,小管的作用类似于脊椎动物的肝脏和免疫系统,以及公认的肾脏功能。为了说明这一点,当只在成年果蝇的马氏管中操纵单个基因Cyp6g1的水平时,1,1,1-三氯-2,2-二(4-氯苯基)乙烷(DDT)攻击后整个昆虫的存活率发生了变化,而神经系统或脂肪体中的相应操纵则没有效果。这表明,尽管解毒酶分布广泛,但对DDT的基线保护主要存在于昆虫排泄系统中,相当于不到生物体质量的0.1%。
Insecticide resistance is a major problem for both medicine and agriculture and is frequently associated with overexpression of metabolic enzymes that catalyze the breakdown of pesticides, leading to broad-spectrum resistance. However, the insect tissues within which these metabolic enzymes normally reside remain unclear. Microarray analysis of nine adult tissues fromDrosophila melanogasterreveals that cytochromeP-450s and glutathione-S-transferases show highly tissue-specific expression patterns; most were confined to one or more epithelial tissues, and half showed dominant expression in a single tissue. The particular detoxifying enzymes encountered by a xenobiotic thus depend critically on the route of administration. In particular, known insecticide metabolism genes are highly enriched in insect Malpighian (renal) tubules, implicating them in xenobiotic metabolism. The tubules thus display, with the fat body, roles analogous to the vertebrate liver and immune system, as well as its acknowledged renal function. To illustrate this, when levels of a single gene,Cyp6g1, were manipulated in just the Malpighian tubules of adultDrosophila, the survival of the whole insect after 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) challenge was altered, whereas corresponding manipulations in the nervous system or the fat body were without effect. This shows that, although detoxification enzymes are widely distributed, baseline protection against DDT resides primarily in the insect excretory system, corresponding to less than 0.1% of the mass of the organism.
DOI: 10.1093/emboj/18.12.3380
发表时间: 1999-06-15
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
Manfruelli, P;Reichhart, JM;Lemaitre, B
通讯作者: Lemaitre, B
DOI: 10.1016/s0965-1748(96)00036-7
发表时间: 1996-07-01
影响因子: 3.8
作者:
Brun, A;Cuany, A;Amichot, M
通讯作者: Amichot, M