Turton H E, Dawes I W, Grant C M
School of Biochemistry and Molecular Genetics and C.R.C. for Food Industry Innovation, University of New South Wales, Sydney, Australia.
J Bacteriol. 1997 Feb;179(4):1096-101. doi: 10.1128/jb.179.4.1096-1101.1997.
Malondialdehyde (MDA) is a highly reactive aldehyde generally formed as a consequence of lipid peroxidation. MDA has been inferred to have mutagenic and cytotoxic roles and possibly to be a participant in the onset of atherosclerosis. Wild-type Saccharomyces cerevisiae acquires resistance to a lethal dose (5 mM) of MDA following prior exposure to a nonlethal concentration (1 mM). This response was completely inhibited by cycloheximide (50 microg ml(-1)), indicating a requirement for protein synthesis for adaptation. Furthermore, we have examined the roles of glutathione (GSH), mitochondrial function, and yAP-1-mediated transcription in conferring resistance and adaptation to MDA. A yap1 disruption mutant exhibited the greatest sensitivity and was unable to adapt to MDA, implicating yAP-1 in both the adaptive response and constitutive survival. The effect of MDA on GSH mutants indicated a role for GSH in initial resistance, whereas resistance acquired through adaptation was independent of GSH. Likewise, respiratory mutants (petite mutants) were sensitive to MDA but were still able to mount an adaptive response similar to that of the wild type, excluding mitochondria from any role in adaptation. MDA was detected in yeast cells by the thiobarbituric acid test and subsequent high-pressure liquid chromatography separation. Elevated levels were detected following treatment with hydrogen peroxide. However, the MDA-adaptive response was independent of that to H2O2.
丙二醛（MDA）是一种高反应性醛类，通常由脂质过氧化作用形成。据推测，MDA具有致突变和细胞毒性作用，可能参与动脉粥样硬化的发病过程。野生型酿酒酵母在预先暴露于非致死浓度（1 mM）的MDA后，会获得对致死剂量（5 mM）MDA的抗性。这种反应被环己酰亚胺（50 μg ml⁻¹）完全抑制，表明适应过程需要蛋白质合成。此外，我们研究了谷胱甘肽（GSH）、线粒体功能以及yAP-1介导的转录在赋予对MDA的抗性和适应性方面的作用。yap1缺失突变体表现出最大的敏感性，无法适应MDA，这表明yAP-1在适应性反应和组成性存活中均起作用。MDA对GSH突变体的影响表明GSH在初始抗性中起作用，而通过适应获得的抗性与GSH无关。同样，呼吸突变体（小菌落突变体）对MDA敏感，但仍能产生与野生型相似的适应性反应，这排除了线粒体在适应过程中的任何作用。通过硫代巴比妥酸试验及随后的高压液相色谱分离在酵母细胞中检测到了MDA。用过氧化氢处理后检测到MDA水平升高。然而，MDA适应性反应与对H₂O₂的反应无关。
