Formation of a substituted 1,N(6)-etheno-2'-deoxyadenosine adduct by lipid hydroperoxide-mediated generation of 4-oxo-2-nonenal.
Formation of a substituted 1,N(6)-etheno-2'-deoxyadenosine adduct by lipid hydroperoxide-mediated generation of 4-oxo-2-nonenal.
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DOI：
10.1021/tx0000771
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发表时间：
2000-09
影响因子：
4.1
通讯作者：
D. Rindgen;S. H. Lee;M. Nakajima;I. Blair
中科院分区：
文献类型：
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作者：
D. Rindgen;S. H. Lee;M. Nakajima;I. Blair
通过液相色谱/恒定中性损失质谱法对2 '-脱氧腺苷和13-氢过氧亚油酸之间的反应进行分析，发现存在两种主要产物（加合物A和B）。加合物A被证明是两种异构体（A（1）和A（2））的混合物，每种异构体在失去水的情况下分解形成加合物B。加合物B的质谱特征与取代的1，N（6）-乙烯基-2 '-脱氧腺苷加合物1“"-[3-（2'-脱氧-β-D-吡喃-五呋喃糖基）-3H-咪唑并[2，1-i]嘌呤-7-基]庚-2"-酮一致。当2 ′-脱氧腺苷与合成的4-氧代-2-壬烯醛作用时，形成加合物A（1）、A（2）和B，这表明它是由13-氢过氧亚油酸分解形成的。当13-氢过氧亚油酸和2 '-脱氧腺苷在Fe（II）存在下孵育时，观察到加合物A（1）、A（2）和B的形成速率显著增加。因此，4-氧代-2-壬烯醛最有可能通过均裂过程形成。虽然在4-羟基-2-壬烯醛和2 ′-脱氧腺苷之间的反应中形成了加合物A（1）、A（2）和B，但观察到了许多额外的产物。这表明4-羟基-2-壬烯醛不是由13-氢过氧亚油酸形成4-氧代-2-壬烯醛的前体。这项研究提供了额外的证据，表明4-氧代-2-壬烯醛是脂质过氧化的主要产物，它与DNA有效地反应形成取代的乙烯加合物。
Analysis of the reaction between 2'-deoxyadenosine and 13-hydroperoxylinoleic acid by liquid chromatography/constant neutral loss mass spectrometry revealed the presence of two major products (adducts A and B). Adduct A was shown to be a mixture of two isomers (A(1) and A(2)) that each decomposed with the loss of water to form adduct B. The mass spectral characteristics of adduct B were consistent with the substituted 1, N(6)-etheno-2'-deoxyadensoine adduct 1' '-[3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-3H-imidazo[2, 1-i]purin-7-yl]heptan-2' '-one. Adducts A(1), A(2), and B were formed when 2'-deoxyadenosine was treated with synthetic 4-oxo-2-nonenal, which suggested that it was formed by the breakdown of 13-hydroperoxylinoleic acid. A substantial increase in the rate of formation of adducts A(1), A(2), and B was observed when 13-hydroperoxylinoleic acid and 2'-deoxyadenosine were incubated in the presence of Fe(II). Thus, 4-oxo-2-nonenal was most likely formed by a homolytic process. Although adducts A(1), A(2), and B were formed in the reaction between 4-hydroxy-2-nonenal and 2'-deoxyadenosine, a number of additional products were observed. This suggested that 4-hydroxy-2-nonenal was not a precursor in the formation of 4-oxo-2-nonenal from 13-hydroperoxylinoleic acid. This study has provided additional evidence which shows that 4-oxo-2-nonenal is a major product of lipid peroxidation and that it reacts efficiently with DNA to form substituted etheno adducts.