Transcriptional and antioxidative responses to endogenous polyunsaturated fatty acid accumulation in yeast
Transcriptional and antioxidative responses to endogenous polyunsaturated fatty acid accumulation in yeast
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DOI：
10.1007/s11010-014-2229-6
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发表时间：
2015-01-01
影响因子：
4.3
通讯作者：
Gasparovic, Ana Cipak
中科院分区：
文献类型：
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作者：
Andrisic, Luka;Collinson, Emma J.;Gasparovic, Ana Cipak
多不饱和脂肪酸（PUFAs）的病理生理学与脂质和氧代谢异常有关。特别是，在氧化应激下，PUFA易于通过过氧化作用发生自催化降解，导致形成具有许多潜在有害影响的反应性醛。然而，脂质过氧化引起的病理和代偿机制是非常复杂的，并没有得到充分的理解。在我们的研究中，我们使用酵母能够内源性PUFA合成，以了解PUFA积累对真核生物细胞生理学的影响。探讨了多不饱和脂肪酸在S.表达巴西橡胶树Delta 12-脂肪酸去饱和酶的酿酒酵母在转录水平下调线粒体中的电子传递链组分以及上调戊糖-磷酸途径和脂肪酸β-氧化。有趣的是，虽然在转录水平上没有观察到变化，但两种重要的酶抗氧化剂，过氧化氢酶和谷胱甘肽-S-转移酶的活性在响应PUFA积累时发生了改变。增加的细胞内谷胱甘肽水平进一步表明内源性氧化应激和激活的抗氧化防御机制下的PUFA积累的条件下。最后，我们的数据表明，PUFA在细胞膜引起的代谢变化，这反过来又导致适应内源性氧化应激。
Pathophysiology of polyunsaturated fatty acids (PUFAs) is associated with aberrant lipid and oxygen metabolism. In particular, under oxidative stress, PUFAs are prone to autocatalytic degradation via peroxidation, leading to formation of reactive aldehydes with numerous potentially harmful effects. However, the pathological and compensatory mechanisms induced by lipid peroxidation are very complex and not sufficiently understood. In our study, we have used yeast capable of endogenous PUFA synthesis in order to understand the effects triggered by PUFA accumulation on cellular physiology of a eukaryotic organism. The mechanisms induced by PUFA accumulation in S. cerevisiae expressing Hevea brasiliensis Delta 12-fatty acid desaturase include down-regulation of components of electron transport chain in mitochondria as well as up-regulation of pentose-phosphate pathway and fatty acid beta-oxidation at the transcriptional level. Interestingly, while no changes were observed at the transcriptional level, activities of two important enzymatic antioxidants, catalase and glutathione-S-transferase, were altered in response to PUFA accumulation. Increased intracellular glutathione levels further suggest an endogenous oxidative stress and activation of antioxidative defense mechanisms under conditions of PUFA accumulation. Finally, our data suggest that PUFA in cell membrane causes metabolic changes which in turn lead to adaptation to endogenous oxidative stress.