title: Nicotinamide: a class III HDACi delays in vitro aging of mouse oocytes.
abstract: 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.
authors.affiliation: Division of Biological Science, Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama 649-6493, Japan.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Lee
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishigami
authors.forename: Tomoko
authors.initials: T
authors.lastname: Amano
authors.forename: Kazuya
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hosoi
mesh_terms: D000818:Animals; D017209:Apoptosis; D016922:Cellular Senescence / Q000187:drug effects*; D002875:Chromosomes / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000737:chemistry; D006877:Hydroxamic Acids / Q000737:chemistry; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009536:Niacinamide / Q000737:chemistry*; D009865:Oocytes / Q000187:drug effects*; D018384:Oxidative Stress; D010641:Phenotype; D008941:Spindle Apparatus / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D014404:Tubulin; D009536:Niacinamide; C012589:trichostatin A; D006655:Histone Deacetylases