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Nicotinamide: a Class III HDACi Delays In Vitro Aging of Mouse Oocytes

机译:烟酰胺:III类HDACi延迟小鼠卵母细胞的体外衰老

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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.
机译:排卵后哺乳动物卵母细胞的发育潜力随体内和体外衰老而降低。随着时间的流逝,老化的卵母细胞通常会出现细胞破碎和染色体分散,纺锤体形状异常。以前的研究表明,小鼠卵母细胞中的组蛋白乙酰化在衰老过程中会增加,而用I,II类组蛋白去乙酰化酶(HDACs)抑制剂曲古抑菌素A(TSA)处理会增强乙酰化,即衰老。在这项研究中,我们检查了烟酰胺(NAM)(III类HDAC的抑制剂)对小鼠卵母细胞以及TSA体外老化的影响。我们发现,使用NAM进行的治疗可在长达48小时的培养中显着抑制细胞破碎,纺锤体伸长和星状微管。尽管TSA的存在可在长达36 h的培养过程中部分抑制细胞碎片化和纺锤体延伸,但TSA处理在培养24 h时会引起染色体分散,而在培养48 h时会导致更严重的细胞分裂。此外,我们发现α-微管蛋白,一种非组蛋白,在衰老过程中增加了乙酰化,这表明不仅组蛋白而且非组蛋白的乙酰化也可能随着卵母细胞衰老而增加。因此,这些数据表明蛋白质乙酰化在衰老的卵母细胞中异常调节,这与多种衰老表型有关,并且I / II和III类HDAC在衰老的卵母细胞中可能发挥不同的作用。

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