Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany functional adaptations in cardiac mitochondria from mice fed n-3 polyunsaturated fatty acids.
Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany functional adaptations in cardiac mitochondria from mice fed n-3 polyunsaturated fatty acids.
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DOI：
10.1042/bj20110626
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Shaikh SR
中科院分区：
文献类型：
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作者：
Anderson EJ;Thayne K;Harris M;Carraway K;Shaikh SR
众所周知，富含n-3多不饱和脂肪酸（n-3 PUFA）的饮食对心脏具有治疗潜力，尽管实现这些效果所需的n-3 PUFA饮食的具体定义持续时间仍然未知，其作用机制也是如此。本研究旨在确定在n-3 PUFA的短期（3周）和长期（14周）饮食干预后，心脏线粒体功能和应激耐受性的适应是否明显，并确定这些适应发生的新机制。在饮食干预后，测定小鼠心肌线粒体呼吸（mO 2）、H2 O2释放（mH 2 O2）和钙潴留能力（mCa 2+）。与所有其他组相比，喂食n-3 PUFA 14周的小鼠显示出显著较低的mH 2 O2和较高的mCa 2+。然而，在n-3 PUFA饮食3周后或在喂食缺乏n-3 PUFA的高脂肪饮食14周的小鼠中未观察到显著差异。有趣的是，在14周时，n-3 PUFA小鼠具有显著更高的谷胱甘肽还原酶活性，这反映在GSH/GSSG比率显著更高。4-羟基己烯醛（一种由n-3 PUFA过氧化形成的醛）的蛋白质加合物水平在n-3 PUFA喂养的小鼠中显著升高，甚至在3周时也是如此。这些发现证明了n-3 PUFA对心脏线粒体功能和应激耐受性的明显时间依赖性作用。此外，他们首次提供了直接证据，证明非酶脂质氧化产物的增加先于这些线粒体和氧化还原介导的适应，从而揭示了n-3 PUFA在心脏中作用的新机制。
Diets replete with n-3 poly-unsaturated fatty acids (n-3 PUFAs) are known to have therapeutic potential for the heart, although a specifically defined duration of n-3 PUFA diet required to achieve these effects remains unknown, as does their mechanism of action. This study was undertaken to establish whether adaptations in mitochondrial function and stress tolerance in the heart is evident following a short- (3 weeks) and long-term (14 weeks) dietary intervention of n-3 PUFAs, and to identify novel mechanisms by which these adaptations occur. Mitochondrial respiration (mO2), H2O2 emission (mH2O2) and Ca2+ retention capacity (mCa2+) were assessed in mouse hearts following dietary intervention. Mice fed n-3 PUFA’s for 14 weeks showed significantly lower mH2O2 and greater mCa2+ compared to all other groups. However, no significant differences were observed after 3 weeks of n-3 PUFA diet, or in mice fed a high fat diet devoid of n-3 PUFAs for 14 weeks. Interestingly, at 14 weeks n-3 PUFA mice had significantly greater glutathione reductase activity, reflected by a substantially higher GSH/GSSG ratio. Levels of protein adducts of 4-hydroxyhexenal, an aldehyde formed from peroxidation of n-3 PUFAs, were significantly elevated in n-3 PUFA fed mice, even at 3 weeks. These findings demonstrate distinct time-dependent effects of n-3 PUFAs on mitochondrial function and stress tolerance in the heart. In addition, they are first to provide direct evidence that increases in non-enzymatic lipid oxidation products precede these mitochondrial and redox-mediated adaptations, thereby revealing a novel mechanism for n-3 PUFA action in heart.