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Akt/PKB plays role of apoptosis relay on entry into first mitosis of mouse embryo

Published online by Cambridge University Press:  09 May 2013

Vladimir Baran ,
Dusan Fabian  and
Pavol Rehak
Vladimir Baran*
Affiliation:
Institute of Animal Physiology, Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, Slovakia.
Dusan Fabian
Affiliation:
Institute of Animal Physiology, Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, Slovakia.
Pavol Rehak
Affiliation:
Institute of Animal Physiology, Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, Slovakia.
*
All correspondence to: Vladimir Baran, Institute of Animal Physiology, Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, Slovakia. e-mail: [email protected]
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Summary

The cell-cycle regulators that control meiotic divisions also regulate the events that accompany the oocyte-to-zygote transition. Thus, the meiotic machinery functions as an internal pacemaker that propels the oocyte toward embryogenesis. The preimplantation embryo expresses a number of receptors that are important for initial activity of the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt/PKB) pathway. The complete PI3K-Akt/PKB-CDK1 cascade is implicated as a key regulator of a number of cellular functions. Selective inhibition of protein kinase B (Akt/PKB) with inhibitor SH6 and cyclin-dependent kinase 1 (CDK1) with inhibitor roscovitine arrest development of the 1-cell preimplantation mouse embryo before entry into the first mitosis. The pronuclei of these inhibited embryos migrate to one another, but do not progress to pronuclei envelope breakdown and pronuclear fusion running immediately before the onset of mitosis. SH6-treated 1-cell mouse embryos showed a high occurrence of apoptosis features (nuclear fragmentation, positive terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), active caspase-3 in both cytoplasm and nucleoplasm). In the Akt/PKB-inhibited embryos, the active phosphorylated form Ser473Akt/PKB was not detected in pronuclear areas when compared with inhibitor-free controls. Although CDK1-inhibited 1-cell embryos also failed to enter into the first mitosis, the presence of apoptotic cell death features was not observed. In the roscovitine-treated embryos, Ser473Akt/PKB was detected in the pronuclei independently of CDK1 activity. We conclude that Akt/PKB plays an important role during entry of the 1-cell mouse embryo into the first mitosis, and probably functions as a relay in the cell-cycle stage. We assume that Akt/PKB is the primary target responsible for mediating anti-apoptotic signals in the 1-cell mouse embryo.

Keywords

ApoptosisAkt kinaseMouse zygoteRoscovitineSH6
Type
Research Article
Information
Zygote , Volume 21 , Issue 4 , November 2013 , pp. 406 - 416
Copyright
Copyright © Cambridge University Press 2013 

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