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

• Published in: Cell and tissue research Vol. 358; no. 2; pp. 627 - 632
• Main Authors: Sirotkin, Alexander V, Dekanová, Petra, Harrath, Abdel Halim, Alwasel, Saleh Hamad, Vašíček, Dušan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-11-2014; Springer Berlin Heidelberg; Springer
• Subjects: Animals; Apoptosis; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; caspases; Cell Proliferation; complementary DNA; DNA binding proteins; Enzymes; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; genes; granulosa cells; Granulosa Cells - cytology; Granulosa Cells - metabolism; Human Genetics; immunocytochemistry; mitogen-activated protein kinase; Molecular Medicine; Monomolecular films; NF-kappa B - metabolism; Proteomics; Reproducibility of Results; Short Communication; Sirtuin 1 - metabolism; Sus scrofa; swine; transcription factor NF-kappa B; Transfection; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; NF-κB (p50/p65); Proliferation; Sirtuin 1; Porcine ovarian granulosa cells; p53; Apoptosis
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-014-1940-7

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.