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Interrelationships between sirtuin 1 and transcription factors p53 and NF-κB (p50/p65) in the control of ovarian cell apoptosis and proliferation

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Abstract

The roles of the mTOR system enzyme sirtuin 1 (SIRT1), the transcription factor p53 and the nuclear factor kappaB (NF-κB) and their interrelationships in the control of ovarian function have not been well studied. We examine, in vitro, the involvement of SIRT1, p53 and the p65 and p50 subunits of NFκB and their interrelationships in the control of the apoptosis and proliferation of porcine ovarian granulosa cells. Monolayers of primary granulosa cells were transfected with cDNA constructs encoding SIRT1, p53, p65 or p50 alone or were co-transfected with gene constructs for SIRT1 together with p53, p65 or p50. The accumulation of SIRT1, markers of proliferation (mitogen-activated protein kinase or extracellular-signal-regulated kinases 1,2) and a marker of apoptosis (caspase 3) was detected by immunocytochemistry. Transfection of cells with a SIRT1 gene construct alone promoted the accumulation of SIRT1 and decreased the accumulation of proliferation markers but did not affect the marker of apoptosis. Transfection of cells with gene constructs encoding p53, p50 or p65 decreased the expression of proliferation markers but not the apoptosis marker. Co-transfection of cells with SIRT1 cDNA changed the action of p65 on cell proliferation from inhibitory to stimulatory. SIRT1 overexpression induced the pro-apoptotic action of p53 and p50 but not of p65 constructs. Thus, SIRT1, p53 and NF-κB are involved in the control of both the proliferation and the apoptosis of ovarian cells. These novel data on the cross-talk between the mTOR/SIRT1 system and the transcription factors p53 and NF-κB show both the inhibitory (proliferation) and stimulatory (apoptosis) influences of SIRT1 on transcription factor action in ovarian cells.

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Acknowledgments

The authors express their gratitude to Ž. Kuklová and Ms. K. Tóthová (Animal Production Research Centre Nitra, Slovakia) for skillful help in analysing the samples, to Dr. P. Puigserver and Dr. J. T. Rodgers (John Hopkins University School of Medicine, Baltimore, Maryland, USA) for kindly providing the constructs for SIRT1, to Dr. N. D. Perkins and Dr. C. Duckett (University of Dundee, Dundee, UK) for kindly providing the constructs for the p53, p50 and p65 subunits of NF-κB and to Dr. M. Bauer (Animal Production Research Centre Nitra, Slovakia) for help with the validation of constructs.

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Authors and Affiliations

  1. Constantine The Philosopher University in Nitra, Nitra, Slovakia

    Alexander V. Sirotkin & Petra Dekanová

  2. Animal Production Research Centre Nitra, Hlohovecká 2, 951 41, Luzianky, Nitra, Slovakia

    Alexander V. Sirotkin & Dušan Vašíček

  3. College of Science, King Saud University, Riyadh, Saudi Arabia

    Abdel Halim Harrath & Saleh Hamad Alwasel

Authors
  1. Alexander V. Sirotkin
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  2. Petra Dekanová
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  3. Abdel Halim Harrath
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  4. Saleh Hamad Alwasel
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  5. Dušan Vašíček
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Corresponding author

Correspondence to Alexander V. Sirotkin.

Additional information

These studies were supported by The Ministry of Agriculture of the Slovak Republic, project RUVV 07–13 and the Agency for Support of Research and Development of Slovak Republic (APVV), projects “REPROPLANT” no. APVV-0854–11, “NANOREPRO” no. APVV-4040-11 and “ZDRAVIE” no. 26220220176, supported by the Operational Programme Research and Development funded by the European Regional Development Fund. A.H. Harrath, S.H. Alwasel and A.V. Sirotkin extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through the research group project NoRGP-VPP-164.

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Sirotkin, A.V., Dekanová, P., Harrath, A.H. et al. Interrelationships between sirtuin 1 and transcription factors p53 and NF-κB (p50/p65) in the control of ovarian cell apoptosis and proliferation. Cell Tissue Res 358, 627–632 (2014). https://doi.org/10.1007/s00441-014-1940-7

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  • DOI: https://doi.org/10.1007/s00441-014-1940-7

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