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黄曲霉毒素及其前体中间体产生过程中氧化应激的生化分析。

Biochemical analysis of oxidative stress in the production of aflatoxin and its precursor intermediates.

作者信息

Narasaiah Kolliputi V, Sashidhar R B, Subramanyam C

机构信息

Department of Biochemistry, University College of Science, Osmania University, Hyderabad, 500 007, India.

出版信息

Mycopathologia. 2006 Sep;162(3):179-89. doi: 10.1007/s11046-006-0052-7.

DOI:10.1007/s11046-006-0052-7
PMID:16944285
Abstract

The relevance of oxidative stress in the production of aflatoxin and its precursors was examined in different mutants of Aspergillus parasiticus, which produce aflatoxin or its precursor intermediates, and compared with results obtained from a non-toxigenic strain. In comparison to the non-toxigenic strain (SRRC 255), an aflatoxin producing strain (NRRL 2999) or mutants that accumulate aflatoxin precursors such as norsolorinic acid (by SRRC 162) or versicolorin (by NRRL 6196) or O-methyl sterigmatocystin (by SRRC 2043) had greater oxygen requirements and higher contents of reactive oxygen species. These changes were in the graded order of NRRL 2999 > SRRC 2043 > NRRL 6196 > SRRC 162 > SRRC 255, indicating incremental accumulation of reactive oxygen species, being least in the non-toxigenic strain and increasing progressively during the ternary steps of aflatoxin formation. Oxidative stress in these strains was evident by increased activities of xanthine oxidase and free radical scavenging enzymes (superoxide dismutase and glutathione peroxidase) as compared to the non-toxigenic strain (SRRC 255). Culturing the toxigenic strain in presence of 0.1-10 muM H(2)O(2 )in the medium resulted in enhanced aflatoxin production, which could be related to dose-dependent increase in [(14)C]-acetate incorporation into aflatoxin B(1) and increased acetyl CoA carboxylase activity. The combined results suggest that formation of secondary metabolites such as aflatoxin and its precursors by A. parasiticus may occur as a compensatory response to reactive oxygen species accumulation.

摘要

在寄生曲霉的不同突变体中研究了氧化应激在黄曲霉毒素及其前体产生过程中的相关性,这些突变体可产生黄曲霉毒素或其前体中间体,并与从非产毒菌株获得的结果进行比较。与非产毒菌株(SRRC 255)相比,产黄曲霉毒素菌株(NRRL 2999)或积累黄曲霉毒素前体如诺索林酸(由SRRC 162产生)、杂色曲霉素(由NRRL 6196产生)或O - 甲基柄曲霉素(由SRRC 2043产生)的突变体具有更高的需氧量和更高的活性氧含量。这些变化呈NRRL 2999 > SRRC 2043 > NRRL 6196 > SRRC 162 > SRRC 255的梯度顺序,表明活性氧的积累逐渐增加,在非产毒菌株中最少,并在黄曲霉毒素形成的三个步骤中逐渐增加。与非产毒菌株(SRRC 255)相比,这些菌株中的氧化应激通过黄嘌呤氧化酶和自由基清除酶(超氧化物歧化酶和谷胱甘肽过氧化物酶)活性的增加而明显。在培养基中存在0.1 - 10μM H₂O₂的情况下培养产毒菌株会导致黄曲霉毒素产量增加,这可能与[¹⁴C] - 乙酸掺入黄曲霉毒素B₁的剂量依赖性增加以及乙酰辅酶A羧化酶活性增加有关。综合结果表明,寄生曲霉产生黄曲霉毒素及其前体等次生代谢产物可能是对活性氧积累的一种补偿反应。

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