Maternal fructose-induced oxidative stress occurs via Tfam and Ucp5 epigenetic regulation in offspring hippocampi.
Maternal fructose-induced oxidative stress occurs via Tfam and Ucp5 epigenetic regulation in offspring hippocampi.
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母体果糖诱导的氧化应激通过子代海马中的 Tfam 和 Ucp5 表观遗传调控发生。
DOI：
10.1096/fj.201901072r
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Hashimoto S
中科院分区：
文献类型：
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作者：
Yamada H;Munetsuna E;Yamazaki M;Mizuno G;Sadamoto N;Ando Y;Fujii R;Shiogama K;Ishikawa H;Suzuki K;Shimono Y;Ohashi K;Hashimoto S
全球果糖消费量正在上升，但母亲高果糖摄入量可能会对后代产生不利影响。我们先前的报告表明，过量的母体果糖摄入会损害子代的海马体功能，这表明子代的海马体对母体果糖高度敏感。在这里，我们研究了母体高果糖对线粒体生理和解偶联蛋白(UCP)表达的影响。大鼠在怀孕和哺乳期间接受20%的果糖溶液。断奶后立即分离子代海马区。母亲高果糖摄入降低了子代海马区线粒体O2的消耗速率，并刺激了脂质过氧化氢的产生。母鼠暴露果糖后，Ucp5和线粒体转录因子A(Tfam)的mRNA水平也降低。我们评估了这两个基因的启动子区域，发现这种处理提高了DNA甲基化水平。此外，荧光素酶分析表明，这种DNA甲基化可以减少这两个基因的转录。染色质免疫沉淀分析表明，DNA甲基化降低了特异性蛋白1与Ucp5启动子区域的结合。此外，Ucp5基因敲除诱导了大鼠脑胶质瘤细胞系中氧自由基水平的上调，而Tfam基因敲除则减少了O2的消耗。因此，母体高果糖摄入导致后代氧气消耗减少和氧化应激增加，至少部分是通过涉及Ucp5和Tfam的表观遗传机制。-Yamada，H.，Munetsuna，E.，Yamazaki，M.，Mizuno，G.，Sadamoto，N.，Ando，Y.，Fujii，R.，Shiogama，K.，Ishikawa，H.，Suzuki，K.，Shimono，Y.，Ohashi，K.，Hashimoto，S.母体果糖诱导的氧化应激发生在子代海马体中。FASE B J.33,11431-11442(2019年)。Www.fasebj.org
Fructose consumption is rising globally, but maternal high fructose intake might adversely affect offspring. Our previous report demonstrated that excess maternal fructose intake impairs hippocampal function in offspring, indicating that the hippocampi of offspring are highly sensitive to maternal fructose. Here, we examined the effect of maternal high fructose on mitochondrial physiology and uncoupling protein (UCP) expression. Rat dams received a 20% fructose solution during gestation and lactation. Immediately after weaning, offspring hippocampi were isolated. Maternal high fructose consumption attenuated the mitochondrial O2consumption rate and stimulated lipid hydroperoxide production in the hippocampi of offspring. ReducedUcp5and mitochondrial transcription factor A (Tfam) mRNA levels were also observed after maternal exposure to fructose. We assessed the promoter regions of both genes and found that this treatment enhanced DNA methylation levels. In addition, luciferase assays showed that this DNA methylation could reduce the transcription of both genes. Chromatin immunoprecipitation analysis demonstrated that specificity protein 1 binding to theUcp5promoter regions was reduced by DNA methylation. In addition,Ucp5knockdown induced the up‐regulation of reactive oxygen species levels in a rat brain glioma cell line, whereas reduced O2consumption was observed withTfamknockdown. Maternal high fructose intake thus induces reduced O2oxygen consumption and increases oxidative stress in offspring, at least partly through epigenetic mechanisms involvingUcp5andTfam.—Yamada, H., Munetsuna, E., Yamazaki, M., Mizuno, G., Sadamoto, N., Ando, Y., Fujii, R., Shiogama, K., Ishikawa, H., Suzuki, K., Shimono, Y., Ohashi, K., Hashimoto, S. Maternal fructose‐induced oxidative stress occursvia TfamandUcp5epigenetic regulation in offspring hippocampi. FASEB J. 33, 11431–11442 (2019). www.fasebj.org