Epoxide Reduction to an Alcohol: A Novel Metabolic Pathway for Perylene Quinone-Type Alternaria Mycotoxins in Mammalian Cells
Epoxide Reduction to an Alcohol: A Novel Metabolic Pathway for Perylene Quinone-Type Alternaria Mycotoxins in Mammalian Cells
复制标题
DOI：
10.1021/tx400366w
复制
发表时间：
2014-02-01
影响因子：
4.1
通讯作者：
Metzler, Manfred
中科院分区：
文献类型：
--
作者：
Fleck, Stefanie C.;Pfeiffer, Erika;Metzler, Manfred
苝醌型链格孢属毒素组含有几种具有环氧基团的同源物，例如，链格孢毒素II（ATX II）和茎叶毒素III（STTX III）。我们实验室最近的研究已经公开了ATX II和STTX III的环氧化物部分在人结肠Caco-2细胞中被还原为醇，从而导致altertoxin I（分别为ATX 0和alterichin）的形成。在本研究中，在其他三种哺乳动物细胞系中证明了ATX II的这种途径。此外，该毒素与谷胱甘肽等单硫醇类化合物发生了化学反应，并通过紫外光谱和质谱初步确定了反应产物的结构。ATX II与能够形成五元环和六元环的二硫醇的化学反应产生ATX I，从而为ATX II的环氧化物还原途径的分子机制提供线索。环氧化物还原和谷胱甘肽结合似乎减弱但不能完全消除ATX II的遗传毒性。
The group of perylene quinone-type Alternaria toxins contains several congeners with epoxide groups, for example, altertoxin II (ATX II) and stemphyltoxin III (STTX III). Recent studies in our laboratory have disclosed that the epoxide moieties of ATX II and STTX III are reduced to alcohols in human colon Caco-2 cells, thereby resulting in the formation of altertoxin I (ATX 0 and alteichin, respectively. In the present study, this pathway was demonstrated for ATX II in three other mammalian cell lines. Furthermore, the chemical reaction of this toxin with monothiols like glutathione could be shown, and the structures of the reaction products were tentatively elucidated by UV and mass spectrometry. Chemical reaction of ATX II with dithiols capable of forming five- and six-membered rings gave rise to ATX I, thus providing a clue for the molecular mechanism of the epoxide reduction pathway of ATX II. Both epoxide reduction and glutathione conjugation appear to attenuate, but not completely abolish, the genotoxicity of ATX II.