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Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro

Artikel i vetenskaplig tidskrift
Författare Linus Ruijin Shao
Emilia Rung
Birgitta Weijdegård
Håkan Billig
Publicerad i Molecular reproduction and development
Volym 73
Nummer/häfte 1
Sidor 50-60
ISSN 1040-452X (Print)
Publiceringsår 2006
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Sidor 50-60
Språk en
Länkar dx.doi.org/10.1002/mrd.20386
Ämnesord Animals, Apoptosis/*physiology, Caspase 3, Caspases/metabolism, Cell Nucleus/metabolism, Cells, Cultured, Ceramides/physiology, Female, Granulosa Cells/*metabolism, Mice, Mice, Inbred C57BL, Receptors, Progesterone/metabolism, SUMO-1 Protein/biosynthesis/*genetics
Ämneskategorier Medicin och Hälsovetenskap, Fysiologi

Sammanfattning

The small ubiquitin-related modifier-1 (SUMO-1) with broad cellular expression has been implicated in a range of cellular processes, such as cell proliferation, differentiation, and apoptosis. As shown recently, SUMO-1 is expressed and regulated by gonadotropins, in particular an ovulatory hCG stimulus in mouse granulosa cells in vivo. To test the hypothesis that modulation of granulosa cell apoptosis changes SUMO-1 expression during granulosa cell differentiation in the mouse ovary, we demonstrate that progesterone receptor (PR) proteins are absent in pre-ovulatory granulosa cell nuclei, whereas they are expressed in periovulatory granulosa cell nuclei in parallel with decreases in SUMO-1 expression, caspase-3 activation, and DNA fragmentation in vivo. Second, treatment with either PR antagonists or a cell permeable ceramide analog consistently increases SUMO-1 expression in parallel with an increase in apoptosis as well as a decrease in cell proliferation in periovulatory granulosa cells in vitro. However, we do not observe an increase in SUMO-1 expression in pre-ovulatory granulosa cells that have undergone the same treatment. Third, we have also demonstrated, in pre-ovulatory granulosa cells in vitro, neither induction of spontaneous apoptosis nor the protective effect of EGF against spontaneous apoptosis changes SUMO-1 protein expression. Fourth, we show that induction of apoptosis enhances SUMO-1 conjugation in periovulatory granulosa cells in vitro, pointing to the pivotal link between the SUMO-1 conjugation and cell death. Taken together, our observations suggest that SUMO-1 via sumoylation has an important role in the regulation of granulosa cell apoptosis during granulosa cell differentiation in the mouse ovary.

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