Nicotinamide: a class III HDACi delays in vitro aging of mouse oocytes.
Nicotinamide: a class III HDACi delays in vitro aging of mouse oocytes.
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DOI：
10.1262/jrd.2012-171
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Hosoi Y
中科院分区：
文献类型：
--
作者：
Lee AR;Kishigami S;Amano T;Matsumoto K;Wakayama T;Hosoi Y
在体内和体外，排卵后哺乳动物卵母细胞的发育潜力随着年龄的增长而降低。随着时间的推移，老化的卵母细胞通常表现为细胞碎裂和染色体散布，出现异常形状的纺锤体。先前的研究表明，小鼠卵母细胞中的组蛋白乙酰化在衰老过程中增加，而曲古抑菌素A(TSA)是一种组蛋白I和II类脱乙酰酶(HDAC)的抑制剂，它能促进组蛋白乙酰化，即衰老。在这项研究中，我们研究了烟酰胺(NAM)，一种III型HDACs的抑制剂，对小鼠卵母细胞体外老化和TSA的影响。我们发现，NAM处理显著抑制了培养48h的细胞碎裂、纺锤体伸长和星形微管。尽管TSA的存在部分抑制了培养36h的细胞碎裂和纺锤体的伸长，但TSA处理在培养的24h导致了染色体的分散，并在培养的48h导致了更严重的细胞碎裂。此外，我们发现α-微管蛋白是一种非组蛋白蛋白，随着年龄的增长，乙酰化程度增加，这表明不仅组蛋白，非组蛋白蛋白的乙酰化程度也可能随着卵母细胞的老化而增加。因此，这些数据表明，蛋白质乙酰化在老化卵母细胞中被异常调节，这与多种衰老表型有关，I/II类和III类HDAC可能在卵母细胞老化中起着不同的作用。
Postovulatory mammalian oocyte developmental potential decreases with aging in vivo and in vitro. Aging oocytes typically show cellular fragmentation and chromosome scattering with an abnormally shaped spindle over time. Previously, it was shown that histone acetylation in the mouse oocyte increased during aging and that treatment with trichostatin A (TSA), an inhibitor for class I and II histone deacetylases (HDACs), enhanced the acetylation, that is, aging. In this study, we examined the effect of nicotinamide (NAM), an inhibitor for class III HDACs, on in vitro aging of mouse oocytes as well as TSA. We found that treatment with NAM significantly inhibited cellular fragmentation, spindle elongation and astral microtubules up to 48 h of culture. Although presence of TSA partially inhibited cellular fragmentation and spindle elongation up to 36 h of culture, treatment with TSA induced chromosome scattering at 24 h of culture and more severe cellular fragmentation at 48 h of culture. Further, we found that α-tubulin, a nonhistone protein, increased acetylation during aging, suggesting that not only histone but nonhistone protein acetylation may also increase with oocyte aging. Thus, these data indicate that protein acetylation is abnormally regulated in aging oocytes, which are associated with a variety of aging phenotypes, and that class I/II and class III HDACs may play distinct roles in aging oocytes.
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