Tubastatin A inhibits HDAC and Sirtuin activity rather than being a HDAC6-specific inhibitor in mouse oocytes.

Abstract:

:Tubastatin A (TubA) is a highly selective histone deacetylase 6 (HDAC6) inhibitor. As expected, mouse germinal vesicle oocytes fail to extrude the first polar body following TubA treatment. However, a previous study demonstrated that homozygous Hdac6 knockout (KO) mice can be viable and fertile. Therefore, we asked whether TubA is indeed a specific inhibitor of HDAC6 activity. RNA-sequencing and in silico analysis demonstrated that the TubA-treated group presented significant changes in the expression of Hdac subfamily genes such as Hdac6, 10, and 11, and Sirtuin 2, 5, 6, and 7. Additionally, gene expression related to the p53, MAPK, Wnt, and Notch signaling pathways in the TubA-treated group were increased significantly; in contrast, gene expression related to metabolism, DNA replication, and oxidative phosphorylation was decreased significantly. Furthermore, gene expression related to cell cycle, cell structure, pyrimidine metabolism, pentose phosphate pathway, mitochondrial activation, proteasome pathway, RNA polymerase, DNA replication, cyclin-dependent kinase, nucleolar activity, and MI arrest were significantly decreased, indicating that TubA-induced abnormal meiotic maturation and oocyte senescence may be due to the combined effects of HDAC and Sirtuin inhibition, and not HDAC6 inhibition alone. Thus, we believed that this system could provide a model for monitoring the effects of TubA on mouse oocytes.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Choi YJ,Kang MH,Hong K,Kim JH

doi

10.18632/aging.101867

subject

Has Abstract

pub_date

2019-03-26 00:00:00

pages

1759-1777

issue

6

issn

1945-4589

pii

101867

journal_volume

11

pub_type

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