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

Tubastatin A inhibits HDAC and Sirtuin activity rather than being a HDAC6-specific inhibitor in mouse oocytes. Aging (Albany NY). 2019 Mar 26;: Authors: Choi YJ, Kang MH, Hong K, Kim JH 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...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research