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Hormesis of low-dose inhibition of pAkt1 (Ser473) followed by a great increase of proline-rich inositol polyphosphate 5-phosphatase (PIPP) level in oocytes

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Abstract

Hormesis describes a biphasic dose-response relationship generally characterized by a low-dose excitement and a high-dose inhibition. This phenomenon has been observed in the regulation of cell, organ, and organismic level. However, hormesis has not reported in oocytes. In this study, we observed, for the first time, hormetic responses of PIPP levels in oocytes by inhibitor of Akt1 or PKCδ. The expression of PIPP was detected by qPCR, immunofluorescent (IF), and Western Blot (WB). To observe the changes of PIPP levels, we used the inhibitors against pAkt1 (Ser473) or PKCδ, SH-6 or sotrastaurin with low and/or high-dose, treated GV oocytes and cultured for 4 h, respectively. The results showed that PIPP expression was significantly enhanced when oocytes were treated with SH-6 or sotrastaurin 10 μM, but decreased with SH-6 or sotrastaurin 100 μM. We also examined the changes of PIPP levels when GV oocytes were treated with exogenous PtdIns(3,4,5)P3 or LY294002 for 4 h. Our results showed that PIPP level was enhanced much higher under the treatment of 0.1 μM PtdIns(3,4,5)P3 than that of 1 μM PtdIns(3,4,5)P3, which is consistent with the changes of PIPP when oocytes were treated with inhibitors of pAkt1 (Ser473) or PKCδ. In addition, with PIPP siRNA, we detected that down-regulated PIPP may affect distributions of Akt, Cdc25, and pCdc2 (Tyr15). Taken together, these results show that the relationships between PIPP and Akt may follow the principle of hormesis and play a key role during release of diplotene arrest in mouse oocytes.

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Funding

This work was funded by the National Nature Science Foundation of China Grant (81370712).

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Authors and Affiliations

  1. Department of Physics and Biophysics, School of Fundamental Sciences, China Medical University (CMU), Shenyang, 110122, People’s Republic of China

    Hang Yu

  2. Center Laboratory of the Fourth Affiliated Hospital, China Medical University (CMU), Shenyang, 110032, People’s Republic of China

    Wei Yong, Teng Gao, Man Na, Ye Zhang & Xin Deng

  3. International Education School of CMU, Shenyang, 110032, People’s Republic of China

    Isaac Harlison Kuguminkiriza & Anyanyo Alexander Kenechukwu

  4. Department of Biochemistry and Molecular Biology, CMU, Shenyang, China

    Qingguo Guo

  5. Institute of Veterinary Medicine, The Academy of Military Medical Sciences of PLA, Changchun, 130122, Jilin, People’s Republic of China

    Guoli Zhang

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  1. Hang Yu
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  2. Wei Yong
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  3. Teng Gao
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  4. Man Na
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  5. Ye Zhang
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  8. Qingguo Guo
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  9. Guoli Zhang
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  10. Xin Deng
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Correspondence to Xin Deng.

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Editor: Tetsuji Okamoto

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Yu, H., Yong, W., Gao, T. et al. Hormesis of low-dose inhibition of pAkt1 (Ser473) followed by a great increase of proline-rich inositol polyphosphate 5-phosphatase (PIPP) level in oocytes. In Vitro Cell.Dev.Biol.-Animal 57, 342–349 (2021). https://doi.org/10.1007/s11626-021-00546-w

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  • DOI: https://doi.org/10.1007/s11626-021-00546-w

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