Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg

Autor: Woojin Kang, Hidekazu Saito, Mami Miyado, Akihiro Umezawa, Natsuko Kawano, Keiichi Yoshida, Maki Iwai, Kenji Miyado, Akihiro Nakamura, Toshio Hamatani, Yoshitaka Miyamoto, Maito Hanai
Rok vydání: 2018
Předmět:
Zdroj: Reproductive Toxicology. 76:71-77
ISSN: 0890-6238
DOI: 10.1016/j.reprotox.2018.01.001
Popis: The ubiquitin-proteasome system, which is initiated by a single ubiquitin-activating enzyme E1 (UBE1), is involved in male reproduction via spermatogenesis and function in mammals. Here we explored the influence of UBE1-specific inhibitor, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (pyrazone-41 or PYR-41) in female reproduction. UBE-1 was detected by immunoblotting and immunocytochemistry in mouse eggs and was localized mainly under the egg plasma membrane. PYR-41 pretreatment suppresses the development of eggs into two-cell embryos. Specifically, pretreatment retarded sperm enlargement and meiotic chromosomal division after sperm-egg fusion. PYR-41 pretreatment disturbed β-catenin, a well-known target protein for ubiquitination, localization under the egg plasma membrane and on spindle microtubules in wild-type eggs. Otherwise, PYR-41 treatment had no effect on the two-cell development of eggs lacking β-catenin. Our results raise the possibility that inhibition of the ubiquitin-proteasome system suppresses sperm enlargement through impaired β-catenin-mediated mechanism.
Databáze: OpenAIRE
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